Neuroprotective Effects of P-Coumaric Acid on Haloperidol-Induced Catalepsy Through Ameliorating Oxidative Stress and Brain Dopamine Level

Objective To evaluate the effect of p-coumaric acid (p-CA) on haloperidol-induced catalepsy in Swiss albino male mice. Method To induce catalepsy, haloperidol (1 mg/kg i.p.) was administered for 21 consecutive days. p-CA (50, 75, and 100 mg/kg, PO) was administered 30 min before haloperidol injection for 21 consecutive days. For catalepsy, locomotor activity and motor coordination scores were recorded on the 17, 14, and 21 days of drug treatment, while the gait analysis score was recorded on day 21. After behavioral testing, animals were sacrificed, and various biochemical and histopathology tests of the brain were conducted. Dopamine, malondialdehyde, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activity were examined in the brain. Results Chronic administration of haloperidol significantly increased catalepsy in mice. It also produced hypolocomotion, motor coordination, and gait disturbance in mice. p-CA significantly inhibited haloperidol-induced catalepsy. Haloperidol significantly increased malondialdehyde levels in the brain. While dopamine levels in the brain dropped along with GSH, SOD, and catalase activity levels, which also had an impact on the histology of the brain. p-CA significantly reduced haloperidol-induced increases in brain oxidative stress, dopamine levels in the brain, and brain histology in mice. Discussion p-CA significantly reduced haloperidol-induced catalepsy, possibly through reducing oxidative stress and increasing brain dopamine levels. It can be a good candidate drug for extrapyramidal symptoms in Parkinson’s disease and adjuvant therapy with antipsychotic drugs.

Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Desenvolvimento motor de escolares de uma cidade da região do Vale do Rio dos Sinos, Rio Grande do Sul, Brasil / Motor development of schools in a city in the Valedo Rio dos Sinos region, Rio Grande do Sul, Brazil

O presente estudo, descritivo, de caráter quantitativo, transversal, buscou avaliar e comparar o desenvolvimento motor de escolares de 8 a 10 anos de idade, da cidade de Novo Hamburgo, estado do Rio Grande do Sul, Brasil. Participaram do estudo 145 escolares (80 meninos e 65 meninas) matriculados na rede municipal de ensino, pertencentes a diferentes escolas e regiões do mesmo município. Como instrumento, foi utilizado o Test of Gross Motor Development - Second Edition (TGMD-2). A análise dos dados foi realizada por meio de estatística descritiva, verificando-se médias, medidas de dispersão, frequência e percentual. Para a comparação dos dados, utilizou-se o teste tde Student e Qui-quadrado, assumindo significância quando p ≤ 0,05. Os resultados evidenciaram que, quando comparados por sexo, os escolares não apresentaram diferença estatística significativa. Quando comparados por idade, os investigados apresentaram, em sua maioria, desenvolvimento motor muito pobre, sem diferença estatística significativa. Contudo, quando comparados por escolas, evidenciou-se que as classificações do desenvolvimento motor dos escolares foram pobres e muito pobres com diferenças estatísticas significativas.

This descriptive, quantitative, cross-sectional study sought to evaluate and compare the motor development of schoolchildren aged eight to ten years, from the city of Novo Hamburgo, state of Rio Grande do Sul, Brazil. The study included 145 students (80 boys and 65 girls) enrolled in the municipal school system, belonging to different schools and regions of the same municipality. As an instrument, the Test of Gross Motor Development - Second Edition (TGMD-2). Data analysis was performed Abstract using descriptive statistics, verifying means, dispersion measures, frequency and percentage. For data comparison, Student's t-test and Chi-square test were used, assuming significance when p ≤ 0.05. The results showed that, when compared by gender, the students did not present a statistically significant difference. When compared by age, the investigated subjects had, for the most part, very poor motor development, with no statistically significant difference. However, when compared by schools, it was shown that the motor development classifications of the students were poor and very poor with statistically significant differences.

Nicotine Differentially Modulates Emotional-Locomotor Interactions for Adult or Adolescent Rats / La Nicotina Modula Diferencialmente la Interacción Emoción-Locomoción en Ratas Adolescentes o Adultas

Abstract Previous research has shown that exposure to nicotine and other drugs of abuse stimulate dopaminergic neurons in the mesolimbic circuit. Sustained activation of this circuit by prolonged exposure to drugs promotes locomotor sensitization. However, there are inconsistent reports about nicotine-induced locomotor sensitization when assessed among different developmental stages. We evaluated exploratory behavior on specific areas of the open field as an indicator of behavioral disinhibition and general locomotor activity as an indicator of nicotine-induced locomotor sensitization, to further explore the mechanisms underlying behavioral adaptations to nicotine exposure in animals from different developmental stages. We found that while adolescent and adult rats are equally responsive to nicotine-induced loco-motor sensitization, nicotine disrupts inhibition of risk-related behavior only in adolescent rats. Together, our results suggest that chronic daily exposure to nicotine promotes potentiation of its stimulant effects on locomotor activity. In adolescents, this effect is accompanied by a decreased capacity to inhibit risk-related behaviors under the acute effect of the drug.

Resumen Estudios previos han demostrado que exposición a la nicotina y otras drogas de abuso estimula las neuronas dopa-minérgicas del circuito mesolímbico. La activación sostenida de este circuito por exposición a las drogas promueve la sensibilización locomotriz. La evaluación de este efecto en diferentes etapas del desarrollo ha mostrado evidencia contradictoria sobre la susceptibilidad de adolescentes. En este trabajo exploramos las adaptaciones conductuales a la exposición crónica a nicotina en ratas adolescentes y adultas; para esto, evaluamos el comportamiento exploratorio en áreas específicas del campo abierto como indicador de desinhibición comportamental y el desplazamiento general como indicador de sensibilización locomotriz. Encontramos que, ambos grupos etarios muestran igual sensibilización locomotriz inducida por la nicotina y que la nicotina altera la inhibición del comportamiento relacionado con el riesgo sólo en adolescentes. Estos resultados sugieren que la exposición crónica diaria a la nicotina promueve la potenciación de sus efectos estimulantes sobre la actividad locomotriz y en los adolescentes, este efecto se acompana de una disminución de la capacidad para inhibir conductas relacionadas con el riesgo bajo el efecto agudo de la droga.

Comparative CNS activities of chlorpheniramine maleate, ebastine, and fexofenadine in Swiss albino mice

Background: Not all second-generation antihistamines were devoid of the central nervous system (CNS) effects such as cognitive and psychomotor impairment. Although these drugs penetrate blood–brain barrier (BBB) to lesser extent, many of them have been found to produce dose-related impairment of CNS functions with interdrug differences present among them. Aim and Objective: This study is aimed to analyze and compare the effects of different antihistamines (first and second generation) on the CNS using Swiss albino mice. Materials and Methods: Twenty-four Swiss albino mice of either sex weighing around 25 - 30 g were randomly divided into six groups with six in each group. Antihistamines such as chlorpheniramine maleate (CPM), ebastine, and fexofenadine were administered to respective groups through oral route. Their effects on CNS were evaluated using rotarod and actophotometer. The data were analyzed using statistical methods. Results: CPM produced significant reduction (P < 0.05) in motor coordination and spontaneous locomotor activity. Ebastine does not have any effect on motor coordination but significant reduction (P < 0.05) in spontaneous locomotor activity. Fexofenadine does not have any effect on motor coordination and spontaneous locomotor activity. Conclusion: We conclude that CPM has significant CNS depressant actions, ebastine has minimal CNS depressant actions, and fexofenadine does not have CNS depressant actions.

Repetitive transcranial magnetic stimulation combined with treadmill training can significantly promote the recovery of locomotor function after a spinal cord injury / 中华物理医学与康复杂志

Objective:To explore the effect of combining repetitive transcranial magnetic stimulation (rTMS) with treadmill training in treating spinal cord injury (SCI).Methods:Fifty female Sprague-Dawley rats were randomly divided into a sham-operation (C) group, an SCI group, a treadmill training (TT) group, a treadmill training followed by rTMS (TR) group and an rTMS followed by treadmill training (RT) group. The C group only underwent laminectomy without spinal cord injury, while the model of T9 incomplete spinal cord injury was established in the other groups using the Louisville Injury System Apparatus impactor. One week after the operation the TT began. The TR group received rTMS immediately after the treadmill training and the RT group received it before. The treadmill′s speed started at 3.6m/min and gradually increased to 6m/min within 1 week. There was one 15min session a day, 5 days a week, for 8 weeks in total. The rTMS intensity was 30% of the maximum output intensity at 10Hz in 5s bursts with an interval of 25s. It lasted 10min, for a total of 1000 pulses. Hind limb motor functioning was evaluated using the Basso, Beattie & Bresnahan (BBB) locomotor rating scale and a grid walking test. The H max/M max ratio was used to quantify the excitability of the motor neurons. Immunohistochemistry was employed to detect the expression of 5-hydroxytryptamine (5-HT), 5-hydroxytryptamine 1A receptor (5-HT 1AR) and 5-hydroxytryptamine 2A receptor (5-HT 2AR). Results:The average BBB scores of the RT group were significantly higher than the SCI group′s averages from the 7th to 9th week after the injury. At the ninth week the average BBB score of the RT group was significantly higher than the TT group′s average. At the eighth and ninth week the average BBB scores of the TR group were significantly higher than in the SCI group. The number of drops in the RT group was significantly lower than in the SCI group at the seventh and ninth week. At the ninth week, the number of drops of the TR group was significantly lower compared with the SCI group. The H max/M max ratio of the SCI group was significantly higher than in the C and TR groups at the fifth and ninth week, while that of the TR group was significantly lower than the SCI group′s ratio at the ninth week. The expression of 5-HT, 5-HT 1AR and 5-HT 2AR in the RT and TR groups was significantly higher than in the SCI group, and the relative 5-HT 1AR density of the RT and TR groups was significantly higher than in the SCI and TT groups. Compared with the other 4 groups, the expression of 5-HT 2AR in the SCI group had increased significantly. Conclusions:Combining rTMS with treadmill training can significantly promote the recovery of locomotor function after incomplete spinal cord injury.

The efficacy of immediate implantation of macroporous poly(N-[2-hydroxypropyl]-methacrylamide) hydrogel after laceration spinal cord injury in young rats / Eficacia de la implantación inmediata de hidrogel macroporoso de poli (N- [2-hidroxipropil] - metacrilamida) después de una lesión de la médula espinal en ratas jóvenes

SUMMARY: Spinal cord regeneration after mechanical injury is one of the most difficult biomedical problems. This article evaluates the effect of poly(N-[2-hydroxypropyl]-methacrylamide) hydrogel (PHPMA-hydrogel) on spinal cord regeneration in young rats after lateral spinal cord hemi-excision (laceration) at the level of segments T12-T13 (TrGel group). The locomotor function score (FS) and the paretic hindlimb spasticity score (SS) were assessed according to Basso-Beattie-Bresnahan (BBB) and Ashworth scales, respectively, and compared to a group of animals with no matrix implanted (Tr group). Regeneration of nerve fibers at the level of injury was evaluated at ~5 months after spinal cord injury (SCI). One week after the SCI induction, the FS on the BBB scale was 0.9±0.5 points in the Tr group and 3.6±1.2 points in the TrGel group. In the Tr group, the FS in 5 months was significantly lower than in 2 weeks after SCI, while no significant changes in FS were detected in the TrGel group over the entire observation period. The final FS was 0.8±0.3 points in the Tr group and 4.5±1.8 points in the TrGel group. No significant changes in SS have been observed in the TrGel group throughout the experiment, while the Tr group showed significant increases in SS at 2nd week, 6th week, 3th month and 5th month. The SS in 5 months was 3.6±0.3 points on the Ashworth scale in the Tr group and 1.8±0.7 points in the TrGel group. Throughout the observation period, significant differences in FS between groups were observed only in 5 weeks after SCI, whereas significant differences in SS were observed in 2, 3 and 6-8 weeks post-injury. Glial fibrous tissue containing newly formed nerve fibers, isolated or grouped in small clusters, that originated from the surrounding spinal cord matter have been found between the implanted hydrogel fragments. In conclusion, PHPMA-hydrogel improves recovery of the hindlimb locomotor function and promotes regenerative growth of nerve fibers. Further research is needed to clarify the mechanism of this PHPMA-hydrogel effect.

RESUMEN: La regeneración de la médula espinal después de una lesión mecánica es uno de los problemas biomédicos más difíciles. Este artículo evalúa el efecto del hidrogel de poli (N- [2-hidroxipropil] -metacrilamida) (PHPMA-hidrogel) sobre la regeneración de la médula espinal en ratas jóvenes después de la hemiescisión lateral de la médula espinal (lesión) a nivel de los segmentos T12 - T13 (Grupo TrGel). La puntuación de la función locomotora (FS) y la puntuación de espasticidad parética de las patas traseras (SS) se evaluaron de acuerdo con las escalas de Basso- Beattie-Bresnahan (BBB) y Ashworth, respectivamente, y se compararon con un grupo de animales sin matriz implantada (grupo Tr). Se evaluó la regeneración de las fibras nerviosas al nivel de la lesión ~ 5 meses después de la lesión de la médula espinal (LME). Una semana después de la inducción de SCI, el FS en la escala BBB fue 0,9 ± 0,5 puntos en el grupo Tr y 3,6 ± 1,2 puntos en el grupo TrGel. En el grupo Tr, el FS en 5 meses fue significativamente menor que en 2 semanas después de SCI, mientras que no se detectaron cambios significativos en FS en el grupo TrGel durante el período de observación. El FS final fue de 0,8 ± 0,3 puntos en el grupo Tr y de 4,5 ± 1,8 puntos en el grupo TrGel. No se han obser- vado cambios significativos en SS en el grupo TrGel durante el experimento, mientras que el grupo Tr mostró aumentos significativos en SS en la 2ª semana, 6ª semana, 3º mes y 5º mes. La SS en 5 meses fue de 3,6 ± 0,3 puntos en la escala de Ashworth en el grupo Tr y de 1,8 ± 0,7 puntos en el grupo TrGel. A lo largo del período de observación, se observaron diferencias significativas en FS entre los grupos solo en 5 semanas después de la LME, mientras que se observaron diferencias significativas en SS en 2, 3 y 6-8 semanas después de la lesión. Entre los fragmentos de hidrogel implantados se observó tejido fibroso glial que contenía fibras nerviosas recién formadas, aisladas o agrupadas en pequeños grupos, que se originaban a partir de la materia de la médula espinal circundante. En conclusión, PHPMA-hydrogel mejora la recuperación de la función locomotora de las patas traseras y promueve el crecimiento regenerativo de las fibras nerviosas. Se requieren más estudios para aclarar el mecanismo del efecto de hidrogel PHPMA.

Knee extension strength and handgrip strength are important predictors of Timed Up and Go test performance among community-dwelling elderly women: a cross-sectional study

ABSTRACT BACKGROUND: Handgrip and knee extension strengths have each been used to characterize disability. However, it has been reported that the association between handgrip and knee extension strengths is weak. OBJECTIVE: To evaluate the influence of knee extensor and handgrip muscle strength on Timed Up and Go (TUG) test results among elderly women with worse (≥ 10 seconds) and better (< 10 seconds) performance, after controlling for confounders. DATA AND SETTING: Cross-sectional study on a sample selected according to convenience, carried out in a federal public institution of higher education. METHODS: Assessment of handgrip was carried out using the Jamar dynamometer (Lafayette Instrument Company, Inc., Lafayette, United States). Knee extensor muscle performance was measured using an isokinetic dynamometer (Biodex System 3 Pro; Biodex Medical Systems, Inc., United States), The confounding factors were education, age, comorbidities, body mass index and Geriatric Depression Scale and Human Activity Profile scores. Functional performance was assessed through the TUG test. A backward linear regression model was used. RESULTS: 127 elderly women performed the TUG test in more than 10 seconds and 93 in less than 10 seconds. However, regardless of test performance, handgrip strength and knee extension strength comprised the reduced final model. CONCLUSIONS: Knee extension strength and handgrip strength might be particularly useful indicators for measuring disability.

Acoustic Radiation Force Impulse (ARFI) elastography imaging of equine distal forelimb flexor structures / [Elastografia Acoustic Radiation Force Impulse (ARFI) das estruturas flexoras da porção distal do membro torácico de equinos]

This study set out to determine normal values for acoustic radiation force impulse (ARFI) elastography of the superficial digital flexor tendon, deep digital flexor tendon, accessory ligament of the deep digital flexor tendon and suspensory ligament in horses. Twenty-four horses were submitted to conventional sonographic assessment and elastography imaging (quantitative ARFI method) of distal forelimb tendons and ligaments at nine anatomical regions. Elastograms depicted tendons and ligaments in orange to red tones consistent with greater stiffness. Shear wave velocity was higher in the longitudinal compared to the cross-sectional plane but did not differ significantly between the left and right forelimbs. The suspensory ligament was stiffer compared to remaining structures in the cross-sectional plane. Ligaments were stiffer than tendons and the deep digital flexor tendon was stiffer than the superficial digital flexor tendon in the longitudinal plane. Target structures were stiffer in male compared to female horses and stiffness tended to increase with age. ARFI elastography proved to be a feasible and reproducible imaging modality for assessment of distal forelimb tendons and ligaments in horses. Qualitative features derived from stiffness quantification in these structures can be applied to horses with musculoskeletal disorders, as well as to other animal species.(AU)

Este trabalho objetivou estabelecer valores de referência por meio da elastografia ARFI ("Acoustic Radiation Force Impulse") do tendão flexor digital superficial, tendão flexor digital profundo, ligamento acessório inferior e ligamento suspensor do boleto em equinos hígidos. Vinte e quatro equinos foram submetidos aos exames ultrassonográfico e elastográfico (método ARFI quantitativo) dos tendões e ligamentos da porção distal do membro torácico, em nove regiões anatômicas diferentes. Os elastogramas mostraram tendões e ligamentos de coloração alaranjada a vermelha, que representam maior rigidez. Não houve diferenças em relação ao membro avaliado; as velocidades de cisalhamento foram maiores nos planos longitudinais. No plano transversal, os ligamentos suspensores foram mais rígidos em comparação aos demais. No plano longitudinal, os ligamentos mostraram-se mais rígidos que os tendões, e o tendão flexor digital profundo, mais rígido que o tendão flexor digital superficial. As estruturas mostraram-se mais rígidas nos machos, e houve uma tendência à maior rigidez em animais mais velhos. A elastografia ARFI comprovou ser um método viável e reprodutível para avaliação dos tendões e ligamentos dos membros torácicos de equinos. As características qualitativas obtidas a partir da rigidez dessas estruturas podem ser utilizadas para testes em equinos com distúrbios musculoesqueléticos e também em outras espécies animais.(AU)

Appraising the Neurobehavioural Toxicity Potential of Aqueous Methanol Leaf Extract of Tapinanthus globiferus Growing on Azadirachta indica

The high prevalence and disease burden of anxiety disorders against the paucity and liabilities of existing anxiolytics indicates a need for the discovery of additional/new anti-anxiety agents. However, it is necessary to further screen these new/putative anxiolytic compounds/extracts to rule out the unwanted neurobehavioural toxicities inherent in the existing anti-anxiety drugs. Aqueous methanol leaf extract of Tapinanthus globiferusgrowing on Azadirachta indicahost tree has previouslydemonstrated significant (p<0.05) anxiolytic effects in mice. This study, therefore, set out to counter-screen this extract for locomotion-suppressant, acute amnesic, sedative (myorelaxant) and hypnotic effects using standard mouse behavioural and biochemical paradigms. The leaf extract (150, 500 and 1500 mg/kg) did not cause significant (p>0.05) alterations in spontaneous locomotor activity, motor coordination/balance, sleep onset or duration,but dose-dependent and significant (p<0.05) increases (63.28±5.63, 65.63±4.12 and 69.18±3.69) in novel object recognition indices of extract-treated compared to 51.54±4.03 and 61.06±2.91 scores in diazepam-and aqua-treated mice, respectively.These findings indicate the aqueous methanol leaf extract is mostly devoid of the evaluated neurobehavioural toxicities and may possess short-term memory enhancement property in mice. These findings may justifythe traditional use of Tapinanthus globiferusextracts for memory enhancement

Melatonin decreases cocaine-induced locomotor activity in pinealectomized rats

Objective: Several studies have shown that the time of day regulates the reinforcing effects of cocaine. Additionally, melatonin and its MT1 and MT2 receptors have been found to participate in modulation of the reinforcing effects of such addictive drugs as cocaine. Loss of the diurnal variation in cocaine-induced locomotor sensitization and cocaine-induced place preference has been identified in pinealectomized mice. In addition, several studies in rodents have shown that administration of melatonin decreased the reinforcing effects of cocaine. The objective of this study was to evaluate the effect of melatonin on cocaine-induced locomotor activity in pinealectomized rats at different times of day (zeitgeber time [ZT]4, ZT10, ZT16, and ZT22). Methods: Naïve, pinealectomized Wistar rats received cocaine at different times of day. Melatonin was administered 30 min before cocaine; luzindole was administered 15 min prior to melatonin and 45 min before cocaine. After administration of each treatment, locomotor activity for each animal was recorded for a total of 30 min. Pinealectomy was confirmed at the end of the experiment through melatonin quantitation by ELISA. Results: Cocaine-induced locomotor activity varied according to the time of day. Continuous lighting and pinealectomy increased cocaine-induced locomotor activity. Melatonin administration decreased cocaine-induced locomotor activity in naïve and pinealectomized rats at different times of day. Luzindole blocked the melatonin-induced reduction in cocaine-induced locomotor activity in pinealectomized rats. Conclusion: Given its ability to mitigate various reinforcing effects of cocaine, melatonin could be a useful therapy for cocaine abuse.

Acupuncture improves locomotor activity and learning-memory ability by improving hippocampal cellular autophagy in rats with fetal intrauterine distress / 针刺研究

OBJECTIVE: To investigate the effect of acupuncture stimulation of head acupoints "Jin San Zhen" (JIN's Three Acupuncture Needles Therapy) on behavior reactions, hippocampal neuronal autophagy and expression of autophagy associated proteins (Beclin-1 and light chain 3 Ⅱ/Ⅰ [LC 3 Ⅱ/Ⅰ]) in rats with hypoxic-ischemic brain damage (HIBD) due to fetal intrauterine distress, so as to reveal its underlying mechanisms in improving neonatal HIBD. METHODS: Pregnant SD rats were used in the present study. The HIBD model was established by delayed caesarean delivery and bilateral uterine arteries clipping for 10 minutes. The HIBD rats were randomly divided into model group and acupuncture groups (n＝9 rats in each group). The other 9 rats delivered naturally were used as the normal control group. On day 14 after delivery, the neonatal rats in the acupuncture group received acupuncture stimulation of head acupoints ("Nao San Zhen""Nie San Zhen" and "Zhi San Zhen") by twirling each needle leftward and rightward for 10 times, once a day for 14 d. The open field test and Morris water maze test were used to determine the locomotive activity and spatial learning-memory ability, respectively. The ultrastructure and autophagosomes in the hippocampal neurons were observed by transmission electron microscope. The contents and expression levels of Beclin-1 and LC3 Ⅱ/Ⅰ in the hippocampus tissues were detected by flow cytometry and Western blot, separately. RESULTS: Compared with the normal control group, the time to go out of the central region of open field test, and the escape latency and duration of first platform-quadrant-crossing of spatial exploration of Morris water maze tests were significantly increased (P<0.01，P<0.05，P<0.001), and the total distance and number of activities in the central region, and the target quadrant resistance time and number of platform-cros-sing remarkably decreased in the model group (P<0.01, P<0.05), suggesting a decline of both locomotor activity and learning-memory ability after modeling. The expression level (%) of Beclin-1 protein and ratio of LC3 Ⅱ/Ⅰ proteins were considerably increased in the model group (P<0.01). Following acupuncture interventions, the locomotor activity and spatial learning-memory ability were obviously increased (P<0.05，P<0.01，P<0.001), and the expression of Beclin-1 protein and ratio of LC3 Ⅱ/Ⅰ were further up-regulated relevant to the model group (P<0.001). Moreover, ultrastructural observation showed serrated change of nuclear membrane and widened perinuclear space, vacuolization in the mitochondria, dilation of endoplasmic reticulum and increase of autophagosomes in the hippocampal neurons in the model group. These situations were relatively milder in the acupuncture group. CONCLUSION: Acupuncture of head acupoints of "JIN San Zhen" may increase locomotor activity and learning-memory abi-lity in rats with HIBD due to fetal intrauterine anoxia, which is closely with its effect in promoting hippocampal neuronal autophagy via up-regulating the expression of Beclin-1 and LC3 Ⅱ/Ⅰ.

Mu-Opioid Receptors Expressed in Glutamatergic Neurons are Essential for Morphine Withdrawal / 神经科学通报·英文版

Although opioids still remain the most powerful pain-killers, the chronic use of opioid analgesics is largely limited by their numerous side-effects, including opioid dependence. However, the mechanism underlying this dependence is largely unknown. In this study, we used the withdrawal symptoms precipitated by naloxone to characterize opioid dependence in mice. We determined the functional role of mu-opioid receptors (MORs) expressed in different subpopulations of neurons in the development of morphine withdrawal. We found that conditional deletion of MORs from glutamatergic neurons expressing vesicular glutamate transporter 2 (Vglut2) largely eliminated the naloxone-precipitated withdrawal symptoms. In contrast, conditional deletion of MORs expressed in GABAergic neurons had a limited effect on morphine withdrawal. Consistently, mice with MORs deleted from Vglut2 glutamatergic neurons also showed no morphine-induced locomotor hyperactivity. Furthermore, morphine withdrawal and morphine-induced hyperactivity were not significantly affected by conditional knockout of MORs from dorsal spinal neurons. Taken together, our data indicate that the development of morphine withdrawal is largely mediated by MORs expressed in Vglut2 glutamatergic neurons.

Mu-Opioid Receptors Expressed in Glutamatergic Neurons are Essential for Morphine Withdrawal / 神经科学通报·英文版

Although opioids still remain the most powerful pain-killers, the chronic use of opioid analgesics is largely limited by their numerous side-effects, including opioid dependence. However, the mechanism underlying this dependence is largely unknown. In this study, we used the withdrawal symptoms precipitated by naloxone to characterize opioid dependence in mice. We determined the functional role of mu-opioid receptors (MORs) expressed in different subpopulations of neurons in the development of morphine withdrawal. We found that conditional deletion of MORs from glutamatergic neurons expressing vesicular glutamate transporter 2 (Vglut2) largely eliminated the naloxone-precipitated withdrawal symptoms. In contrast, conditional deletion of MORs expressed in GABAergic neurons had a limited effect on morphine withdrawal. Consistently, mice with MORs deleted from Vglut2 glutamatergic neurons also showed no morphine-induced locomotor hyperactivity. Furthermore, morphine withdrawal and morphine-induced hyperactivity were not significantly affected by conditional knockout of MORs from dorsal spinal neurons. Taken together, our data indicate that the development of morphine withdrawal is largely mediated by MORs expressed in Vglut2 glutamatergic neurons.

Welfare and locomotor system disorders in active draft horses (cart horses) / Bem-estar e afecções do aparelho locomotor de equinos de tração (carroceiros) em atividade

Horses performing tasks is a common scene in urban centers, evidenced by the significant number of animals pulling carts along the streets (cart horses). Despite the rising concern of the population for animal welfare, as well as the creation of laws that prohibit traction activity in several Brazilian municipalities, these attitudes must be based on the impact of such activity on equine health. Locomotor system disorders are commonly observed in animals of this species, and become even more frequent when they are submitted to unhealthy working conditions. In this context, we conducted a survey on locomotor system disorders in 11 active draft horses. To this end, we performed lameness assessments and radiographic and ultrasound examinations. Information on management regarding the horses' hooves, type of harness used, and type of work performed was also obtained through the application of questionnaires to the owners. The collected data showed that, although most of the animals in the study presented critical orthopedic conditions, they were not treated and the horses did not rest for adequate time. We observed that the disorders, which are often chronic, may be directly associated with incorrect management of the animals. We emphasize the importance to disseminate information that values the welfare of traction animals in order to tackle mistreatment.(AU)

Cavalos desempenhando tarefas para o homem é ainda uma cena marcante nos centros urbanos, evidenciada pela grande quantidade de animais que tracionam carroças pelas ruas (carroceiros). Apesar da crescente preocupação da população com o bem estar animal, assim como a criação de leis que proíbem a atividade de tração em diversos municípios brasileiros, é imprescindível que estas atitudes estejam embasadas no impacto de tal atividade sobre a saúde dos equinos. Nesta espécie, afecções do aparelho locomotor são comuns, tornando-se ainda mais frequentes quando os animais são submetidos a condições insalubres de trabalho. Por conseguinte, este estudo promoveu um levantamento das afecções que acometem o aparelho locomotor de 11 equinos de tração em atividade, por meio de exames de claudicação, radiográficos e ultrassonográficos. Informações sobre manejo realizado pelos proprietários quanto aos cascos de seus animais, tipos de arreios utilizados e tipo de trabalho ao qual eram submetidos foram obtidas através de questionários. Verificou-se ao relacionar dados coletados, que a maioria dos animais do estudo apresentava afecções ortopédicas importantes, e que, entretanto, não eram tratados ou mantidos em repouso por tempo adequado. Observou-se que as afecções encontradas, muitas vezes crônicas, podem ter relação direta com o manejo incorreto dos animais, e ressalta-se a importância da disseminação de informações que prezem pelo bem estar do animal de carroça, a fim de combater maus tratos nesta categoria animal.(AU)

Patient safety issues in rehabilitation for person with locomotor disabilities: a review

Since the publication of the Institute of medicine report, To Err Is Human: Building a safer health system, notes that errors in health care are a significant cause of death and injury and the emphasis on patient safety has steadily increased. The rehabilitation professionals engaged for the management of patient with locomotor disabilities should incorporate elements of patient safety into their practices and also to stimulate research associated with prevalence of analysis of error/harm which occurs during the rehabilitation phase and also to develop and validate certain specific measuring tools and instruments for patient safety issues.

Comparative Behavioral Correlation of High and Low-Performing Mice in the Forced Swim Test

Behavioral analysis in mice provided important contributions in helping understand and treat numerous neurobehavioral and neuropsychiatric disorders. The behavioral performance of animals and humans is widely different among individuals but the neurobehavioral mechanism of the innate difference is seldom investigated. Many neurologic conditions share comorbid symptoms that may have common pathophysiology and therapeutic strategy. The forced swim test (FST) has been commonly used to evaluate the “antidepressant” properties of drugs yet the individual difference analysis of this test was left scantly investigated along with the possible connection among other behavioral domains. This study conducted an FST-screening in outbred CD-1 male mice and segregated them into three groups: high performers (HP) or the active swimmers, middle performers (MP), and low performers (LP) or floaters. After which, a series of behavioral experiments were performed to measure their behavioral responses in the open field, elevated plus maze, Y maze, three-chamber social assay, novel object recognition, delay discounting task, and cliff avoidance reaction. The behavioral tests battery revealed that the three groups displayed seemingly correlated differences in locomotor activity and novel object recognition but not in other behaviors. This study suggests that the HP group in FST has higher locomotor activity and novelty-seeking tendencies compared to the other groups. These results may have important implications in creating behavior database in animal models that could be used for predicting interconnections of various behavioral domains, which eventually helps to understand the neurobiological mechanism controlling the behaviors in individual subjects.

Assessment of the single and mixture ecotoxicity of pharmaceuticals of environmental concern using aquatic test organisms / Avaliação da ecotoxicidade individual e das misturas de fármacos de preocupação ambiental usando organismos-teste aquáticos

Pharmaceuticals are contaminants of emerging concern which have been a target of increasing attention by the scientific community. Pharmaceuticals presenting high consumption, incomplete metabolism and incomplete removal at wastewater treatment plants have been frequently detected in aquatic ecosystems worldwide. This is the case of the pharmaceuticals metformin (MET), bisoprolol (BIS), sotalol (SOT) and ranitidine (RAN). However, ecotoxicity data for these contaminants are scarce, especially regarding behavior effects and chronic toxicity. In addition, the knowledge regarding the joint toxicity of these pharmaceuticals on non-target organisms is still incipient, which makes their environment risk assessment uncertain. This study aimed to fill these knowledge gaps for these four pharmaceuticals, by carrying out toxicity tests using five test organisms from three trophic levels. Different endpoints were assessed in tests with Raphidocelis subcapitata (algae), Lemna minor (macrophyte), Daphnia similis (crustacean), Hydra attenuate (cnidarian) and Danio rerio (fish). The binary and quaternary mixture acute toxicity for these pharmaceuticals were assessed on D. similis and D. rerio embryo tests, respectively. This study also aimed to evaluate the predictive accuracy of the Concentration addition (CA) and the Independent action (IA) classic models. In addition, the nature of the possible toxicological interactions between the pharmaceuticals in binary mixtures were also evaluated, using the Combination Index-isobologram (CI) method. The modelling of the concentration-response curves and the associated statistical analyses were performed using the automated spreadsheet ToxCalcMix v.1.0 and the software OriginPro 2015. The software CompuSyn was used for performing the mixture analyses with the CI method. The experimental planning of the binary mixture tests was performed using the fractioned factorial design, in order to cover several possible ratio and level-dependent effects with a reduced number of test organisms. The results obtained in this study are shown in four articles. In article 1, we provided a critical review and discussed the misunderstandings, deficiencies and data gaps on the ecotoxicity data of pharmaceuticals and personal care products mixtures published in the literature. In the following articles, the results obtained from the single and mixture toxicity tests performed in this study were presented and discussed. The pharmaceuticals MET (article 2) and BIS (article 3) were classified as hazardous to the aquatic environment, in the acute toxicity category. However, an ecological risk is not expected for the pelagic freshwater species exposed to these two pharmaceuticals, based on the chronic data obtained. The results obtained from the mixture toxicity tests (article 4) showed that most of the observed toxicity effects from the binary mixtures were in the zone between the predicted effects by the CA and IA models. The CI model showed to be an useful tool to describe the possible toxicological interactions occurring between the pharmaceuticals in joint action. Even statistically significant non-effect concentrations of the pharmaceuticals added up to induce significant adverse effects in mixtures (something from nothing). It was concluded that ecological risk assessment based on single toxic effects can underestimate the real impact of environmental contaminants on aquatic ecosystems

A contaminação ambiental por fármacos tem sido alvo de crescente preocupação pela comunidade científica. Fármacos de elevado consumo, incompleto metabolismo e remoção incompleta em estações de tratamento de esgoto, como é o caso da metformina (MET), bisoprolol (BIS), sotalol (SOT) e ranitidina (RAN), têm sido frequentemente detectados em matrizes aquáticas do mundo todo. Apesar disso, dados ecotoxicológicos consistentes para esses contaminantes são escassos, principalmente com relação a efeitos comportamentais e oriundos de estudos crônicos. Além disso, o entendimento dos efeitos de suas ações combinadas em organismos não-alvo é ainda incipiente, o que gera incertezas na avaliação dos seus riscos ambientais. Esta pesquisa teve por objetivo preencher essas lacunas de conhecimentos para esses quatro fármacos, por meio da realização de testes com cinco diferentes organismos-teste de três diferentes níveis tróficos. Foram analisados diferentes parâmetros avaliativos em testes com os organismos aquáticos Raphidocelis subcapitata (alga), Lemna minor (macrófita), Daphnia similis (crustáceo), Hydra attenuata (cnidário) e Danio rerio (peixe). As toxicidades agudas das misturas binárias e quaternárias desses quatro fármacos também foram avaliadas em testes com D. similis e embriões de D. rerio, respectivamente. Este trabalho também teve por objetivo avaliar a acurácia preditiva dos modelos de adição de concentração (CA) e ação independente (IA) e analisar a natureza das possíveis interações toxicológicas entre os fármacos, em misturas binárias, usando o modelo do Índice de Combinação (CI). A modelagem das relações concentração-resposta e as análises estatísticas associadas foram realizadas empregando-se a planilha automatizada ToxCalcMix versão 1.0 e o software OriginPro 2015. O software CompuSyn foi utilizado para as análises envolvendo o CI. O planejamento experimental dos testes de misturas binárias foi realizado por meio do design fatorial fracionado, a fim de cobrir diversas possíveis interações em várias proporções e níveis de efeitos, com a redução do número de organismos-teste. Os resultados desta pesquisa estão apresentados em quatro artigos. No artigo 1, realizou-se uma revisão crítica com relação às lacunas de conhecimentos e deficiências identificadas a partir da análise da literatura sobre a ecotoxicologia de misturas de fármacos e de produtos de higiene pessoal. Nos artigos seguintes, foram apresentados e discutidos os resultados oriundos dos testes com os quatro fármacos avaliados neste estudo. Os fármacos MET (artigo 2) e BIS (artigo 3) foram classificados como perigosos para o ambiente aquático, na categoria de toxicidade aguda. Contudo, um risco ecológico não é esperado para as espécies pelágicas de água doce expostas a esses dois fármacos, com base nos dados de toxicidade crônica obtidos. Os resultados dos testes de misturas (artigo 4) permitiram concluir que a maior parte dos efeitos observados das misturas binárias estiveram na zona entre os efeitos preditos pelos modelos clássicos de CA e IA. O modelo do CI mostrou-se uma ferramenta útil para descrever a natureza das possíveis interações toxicológicas que ocorrem entre os fármacos em ações combinadas. Mesmo concentrações de nenhum efeito estatisticamente significativo dos fármacos causaram efeitos adversos significativos quando em misturas (something from nothing). Concluiu-se que avaliações de risco ecológicas baseadas em efeitos tóxicos individuais de contaminantes ambientais podem subestimar o real impacto desses compostos em ecossistemas aquáticos

A study on anxiolytic activity and locomotor behavior of Curcuma amada rhizomes using Wistar albino rats

Background: Global burden of disease statistics indicate that 4 of 10 most important causes of disease worldwide are psychiatric in origin. Anxiety affects 1/8th of total population of the world and is a very important area of research interest in psychopharmacology. Medicinal plants and plant products are the oldest tried health-care products. Their importance is growing not only in developing countries but in many developed countries. Curcuma amada Roxb. (CA) commonly known as Mango Ginger is a rhizomatous aromatic herb which is used in this country for culinary purposes and also to treat various diseases. The rhizomes of Curcuma amada was screened for anxiolytic activity and locomotor behavior in Wistar albino rats.Methods: Wistar albino rats were divided into three groups as control (Distilled water with 0.1% CMC), standard (Diazepam - 1mg/kg) and test - Ethanolic Extract of Curcuma amada Rhizome (EECAR-250 mg/kg). They were administered drugs orally for a period of 10 days, and screened for anxiolytic activity using Light dark arena model and Actophotometer for assessing the locomotor behavior on the 10th day. The number of crossings and time spent in light arena for anxiolytic activity, and the number of movements in Actophotometer was noted. Data was analyzed by one way ANOVA followed by Tukey Kramer multiple comparison test using GraphPad InStat software.Results: Curcuma amada (250mg/kg) showed increased time spent in light arena and decreased locomotor behavior which was statistically significant.Conclusions: Curcuma amada possesses significant anxiolytic with CNS depressant activity.

Actividades sobre los conjuntos esqueléticos de cada segmento corporal en la carrera de Cultura Física / Activities on the skeletal assemblies of each body segment in the Physical Culture course

RESUMEN El presente trabajo investigativo surge debido a la necesidad de crear un medio de enseñanza con actividades que les permita a los estudiantes comprobar, de manera sistémica, el aprendizaje de los conocimientos relacionados con los conjuntos esqueléticos de cada segmento corporal del Sistema Locomotor Humano, recibidos en la asignatura Morfología Funcional II, la cual se imparte en el 1er año de la carrera de Cultura Física. El libro de texto de la asignatura no brinda esta posibilidad. Para realizar el estudio se aplicaron fundamentalmente métodos a nivel empíricos, tales como la revisión de documentos, la encuesta y la entrevista. Se trabajó con una muestra de 115 estudiantes de primer año de la carrera y tres profesores, quienes imparten la materia. Las actividades contenidas están organizadas por cada segmento corporal del sistema locomotor humano, según el programa de la asignatura, acompañadas de esquemas y figuras para marcar, identificar, seleccionar, caracterizar y clasificar detalles anatómicos que se precisen, aumentando su nivel de complejidad. Estas actividades se ofrecen además como herramienta para ser utilizada en otras asignaturas del ciclo biológico y del ejercicio de la profesión.

ABSTRACT The research work Activities on skeletal sets of each body segment of the Human Locomotor System in the 1st year of the career of Physical Culture, arises due to the need for a teaching medium for the subject of Functional Morphology II that contains systemically activities that allows the students to check the learning of the knowledge related to the skeletal assemblies of each body segment of the Human Locomotor System, since the subject's textbook does not provide this possibility, which hinders the consolidation of knowledge about sets skeletal of each body segment of the Human Locomotor System, the programmed activities are necessary and essential for the understanding of the work object of the professional of our career and facilitates the acquisition, deepening and consolidation of knowledge about the locomotor system, activities on joint skiing Elastics of each body segment of the Human Locomotor System are also offered as a tool to be used in other subjects of the biological cycle and the exercise of the profession. The activities that are presented are organized by each body segment of the human locomotor system according to the program of the subject, accompanied by diagrams and figures to mark, identify, select, characterize, classify anatomical details that are needed, increasing their level of complexity. It gives solution to the insufficiency of activities that for the teaching and learning process of the skeletal groups of each body segment of the human locomotor system presents the subject of Functional Morphology II and its application in professional work.