Analgesic and neuromotor effects of two extracts of Zanthoxylum rhoifolium (Rutaceae) in the Swiss albino mouse (Mus musculus) / Efectos analgésicos y neuromotores de dos extractos de Zanthoxylum rhoifolium (Rutaceae) en el ratón albino suizo (Mus musculus)

Background: Colombia has a high diversity of medicinal plants, including Tachuelo (Zanthoxylum rhoifolium), a tree belonging to the family Rutaceae, which has been attributed an analgesic use by communities of the Colombian southwest. Nevertheless, this species has been scarce studied in Colombia. The studies have been limited to the isolation of compounds with antifungal and insecticide activity, using the leaves, branches, and bark of the plant in aqueous, and organic extracts. Neither pharmacological tests have been carried out, nor the analgesic and neuromotor activity have been tested from preparations with this plant's fruits. Objectives: To evaluate the analgesic and neuromotor effect of the aqueous and hexane extract of the fruits of Z. rhoifolium.Methods: As there were no preliminary reports of this study, the first observation was made through Irwin's test. The formalin and the rotarod test were performed to determine the analgesic and motor coordination effects, respectively. Results: All the evaluated treatments demonstrated to generate analgesia, anesthesia, passivity, reduction in the alarm reaction, and have antinociceptive activity in the formalin test; while only the high dose of the nonpolar extract generated a deficit in the motor performance of the rodents in the rotarod test. Conclusions: the antinociceptive effect of the aqueous and hexane extracts of this species' fruits was demonstrated. The hexane extract generated a neuromotor effect, which validates the ethnobotanical reports on Z. rhoifolium fruits.

Antecedentes: Colombia tiene una alta diversidad de plantas medicinales, incluyendo al Ta chuelo (Zanthoxylum rhoifolium), un árbol de la familia Rutaceae al que se le ha atribuido un potencial analgésico debido al uso por parte de las comunidades del Suroccidente Colombiano. Sin embargo, esta especie ha sido poco estudiada en Colombia, limitándose al aislamiento de compuestos con actividad antifúngica e insecticida, empleando las hojas, ramas y corteza de la planta en extractos acuosos y orgánicos; sin embargo, no se han realizado ensayos farmacológicos ni se han probado la actividad analgésica y neuromotora a partir de preparaciones con los frutos de esta planta. Objetivos: Evaluar el efecto analgésico y neuromotor del extracto acuoso y en hexano de los frutos de Z. rhoifolium. Métodos: Al no haber reportes preliminares de este estudio, se realizó la primera observación mediante el test de Irwin. Para determinar el efecto analgésico y neuromotor se realizó el test de formalina y el test de rotarod, respectivamente. Resultados: Todos los tratamientos evaluados demostraron generar analgesia, anestesia, pasividad, reducción en la reacción de alarma, tener actividad antinociceptiva en el test de formalina, mientras que solo la dosis alta del extracto apolar generó un déficit en el rendimiento motor de los roedores en el test de rotarod. Conclusiones: Se demostró el efecto antinociceptivo del extracto acuoso y en hexano de los frutos de esta especie y el efecto neuromotor generado por el extracto en hexano, validando los reportes etnobotánicos sobre los frutos de Z. rhoifolium.

Development of a three-channel automatic climbing training system for rat rehabilitation after ischemic stroke

This paper reports the development of a three-channel automatic speed-matching climbing training system that could train three rats at the same time for rehabilitation after an ischemic stroke. An infrared (IR) remote sensor was installed at the end of each channel to monitor the real-time position of a climbing rat. This research was carried out in five stages: i) system design; ii) hardware circuit; iii) running speed control; iv) functional testing; and v) verification using an animal model of cerebral stroke. The rehabilitated group significantly outperformed the middle cerebral artery occlusion (MCAo) sedentary group in the rota-rod and inclined plate tests 21 days after a stroke. The rehabilitated group also had a cerebral infarction volume of 28.34±19.4%, far below 56.81±18.12% of the MCAo group 28 days after the stroke, validating the effectiveness of this training platform for stroke rehabilitation. The running speed of the climbing rehabilitation training platform was designed to adapt to the physical conditions of subjects, and overtraining injuries can be completely prevented accordingly.

Anti-stress activity of Ocimum sanctum and alprazolam in animal models

Background: Stress is the physiological, psychological and behavioral response by individuals when they perceive a lack of equilibrium between the demands placed upon them and their ability to meet those demands, which over a period of time leads to ill health. There are several ways of coping with stress. Some techniques of time management may help a person to control stress.Methods: Forced swim test- mice were randomized into two groups according to the body weights. Each group contains six animals. Each individual animal was allowed to swim inside the jar (25-12-25 cm) containing fresh water up to 15 cm height. Mice were allowed swim for 6 min. After initial struggle to escape the animal became immobile. Total immobility period was measured. Rotarod test- mice were randomized into two groups according to body weights. Each group contains six animals. Rats were placed on the lanes. Latency period was recorded at which each rat falls off the rod.Results: In first experiment, anti-stress activity of Ocimum sanctum in mice was demonstrated by measuring the immobility period during forced swim test and in the second experiment the measurement of the latency period of rats in rotarod apparatus was performed. Both the experimental procedures were compared with standard anti stress drug alprazolam.Conclusions: The present study suggests that Ocimum sanctum possess significant anti stress activity but less when compared to alprazolam.

In-Vivo Study on Anxiolytic Effects of Hydroalcoholic Extract of Agaricus blazei Murill

Background: Anxiety involved panic attacks either having or not having social fear, social anxiety disorder, generalized anxiety disorder as well as separation anxiety disorder is known to be marked mental diseases. It is related to high medical cost and a significant load of disease. Agaricus blazei Murill (AbM) is a mushroom and possesses immunemodulating and antimicrobial effects both in-vivo and in-vitro and as well as it has been used to treat cancer, hepatitis, dermatitis, and hyperlipidemia traditionally. Method: In this experiment evaluation of anxiolytic effect of AbM on mice has been done by using Elevated Plus Maze test, open field test and motor co-ordination test by rotarod. Mice (Mus musculus) weighing 22-25 grams, were divided into 4 groups (n=6). Oral administration of hydro-alcoholic extract of AbM was utilized in 2 doses i.e. 136.5 mg/kg and 273 mg/kg. Group, I received vehicle (distilled water 10 ml/kg), p.o. Group II received standard (diazepam 1 mg/kg), i.p. Group III and IV orally received hydro-alcoholic extract of AbM (136.5 mg/kg and 273 mg/kg, respectively). Result: In Elevated Plus Maze test, oral administration of hydro-alcoholic extract of AbM (136.5 mg/kg and 273 mg/kg, respectively) exhibited significant (p<0.01) elevation in the percentage of number of open arm entries (48.0 ± 1.1% and 48.93 ± 2.1% respectively) and time spent in open arm (14.92 ± 1.9% and 84.17 ± 2.4%). Conclusion: Hence it is concluded that hydro-alcoholic extract of AbM can be a new therapeutic agent to treat anxiety.

Improvements of motor and cognitive functions in the rats with permanent middle cerebral artery occlusion treated with acupuncture and rota-rod training / 中国针灸

OBJECTIVE@#To explore the effects on the recovery of the motor and cognitive functions of the rats with permanent middle cerebral artery occlusion (pMCAO) after treated with 's three-needle acupuncture at head acupoints combined with rota-rod training.@*METHODS@#A total of 38 male SD rats were randomized into 3 groups, named a sham-operation group (11 rats), a model group (13 rats) and a treatment group (14 rats). The electrocoagulation method was adopted to establish the model of pMCAO on the right cerebrum. Starting from the 1st day after successful modeling, acupuncture was applied to the "three points of intelligence", the "three points of temporal area" and the "three points of brain". Additionally, the rota-rod training was used. Acupuncture was given once a day and the training was three times a day. In the sham-operation group and the model group, empty grasp fixation was performed when acupuncture was applied in the treatment group, and there was no intervention at the rest of the time. There was 1 day of interval after consecutive 6 days of intervention. Totally, the intervention was for 3 weeks. After modeling, the brain section was collected from 3 rats of each group on the 1st day and was stained with TTC to observe the condition of cerebral ischemia. From day 1 to 7, the neurological function score was evaluated. The footprint analysis and rota-rod test were performed on day 1, 7, 14 and 21. The Morris water maze test was performed from day 22 to 26.@*RESULTS@#Compared with the sham-operation group, cerebral ischemia presented obviously, the score of neurological function was increased, the back front distances on the left were increased on day 1, 7 and 14 separately, the revolutions per minute (RPM) of the rota-rod were reduced at each of the above 4 time points, the latency of navigation trial was increased and the movement time percentage in Q3 quadrant of spatial probe trial was reduced in the model group (0.05), the score of neurological function was reduced on day 6, the back front distance on the left was reduced on day 14, RPM of the rota-rod were increased on day 14 and 21, the latency of navigation trial were reduced from day 23 to 25 and the movement time percentage in Q3 quadrant of spatial probe trial was increased in the treatment group (<0.01, <0.05).@*CONCLUSION@#'s three-needle acupuncture at head acupoints combined with rota-rod training improve the behavioral performance of pMCAO rats and promote the recovery of motor and cognitive functions.

Effects of fatigue-predominant subhealth on mechanical and thermal pain sensitivity in mice / 中国药理学通报

Aim: To study the effects of the fatigue-predominant subhealth on mechanical and thermal pain sensitivity in mice. Methods: Kunming mice were randomly divided into two groups (n = 10); normal control group (control), fatigue-predominant subhealth model group (fatigue). The physiological behavior, rota-rod test and blood routine indexes were examined. The paw withdrawal mechanical threshold (PWMT) and the paw withdrawal thermal latency (PWTL) were measured in order to reflect the change of the mechanical and thermal pain sensitivity. Results: Compared to control group, the fur of model group was markedly pale, the time of rota-rod test was significantly lower (P < 0. 01), the data of blood cells was nearly the same, the outcome of PWMT was increased (P < 0. 01), and PWTL was decreased (P < 0. 01). Conclusions The fatigue-predominant subhealth reduces the mechanical pain sensitivity and increases the thermal pain sensitivity in mice.

Comparative study of centrally acting skeletal muscle relaxants nitrazepam and thiocolchicoside in Albino mice

Background: Skeletal muscle relaxants are a heterogeneous group of drugs. As a group, they are structurally and pharmacologically diverse. Skeletal muscle relaxants are usually used as adjunct therapy when initial therapy fails. They are commonly used to treat fibromyalgia, low back pain, neck pain, tension head ache, myofascial pain and muscle spasm.Methods: There were 28 mice were randomly divided into seven groups, each group consists of 4 mice. Group 1(Control): Mice were treated with normal saline and placed on rotating rod with a speed of 18 rpm (ideal speed). Group 2 (Standard-S1): Mice were treated with Nitrazepam at the dose of 2mg/kg body weight and placed on rotating rod. Group 3 (Standard-S2): Mice were treated with Nitrazepam at the dose of 3mg/kg body weight and placed on rotating rod. Group 4 (Standard-S3): Mice were treated with Nitrazepam at the dose of 4mg/kg body weight and placed on rotating rod. Group 5 (Test-T1): Mice were treated with Thiocolchicoside at the dose of 2mg/kg body weight and placed on rotating rod. Group 6 (Test-T2): Mice were treated with Thiocolchicoside at the dose of 3mg/kg body weight and placed on rotating rod. Group 7 (Test-T3): Mice were treated with Thiocolchicoside at the dose of 4mg/kg body weight and placed on rotating rod.Results: In this model inter drug comparisons were carried out with nitrazepam and thiocolchicoside. It was found that both nitrazepam and thiocolchicoside produced central muscle relaxant effect when assessed by rotarod. On iter drug comparision of nitrazepam and thiocolchicoside it was found that by increasing concentration of drug, increased the muscle relaxant property.Conclusions: When assessed by rotarod, it was found that both nitrazepam and thiocolchicoside demonstrated muscle relaxant property but with increased doses of thiocolchicoside produced more muscle relaxant property than the increase in doses of nitrazepam.

A Study on the Behaviour of Huntington’s Chorea Rat Models on Rotarod: Treated with Withanolide a and the Ethanolic Extract of Withania Somnifera.

Background: Huntington’s disease (HD) is a fatal neurodegenerative disease named after George Summer Huntington who first described the disorder in 1872. Huntington’s disease is associated with basal ganglia degeneration which is called as the controlling center of extra pyramidal motor system that exerts an inhibitory effect on cerebral motor cortex. This will filters the unwanted motor movements and so refines the motor movements. Degeneration of neurons of basal ganglia reduces the inhibitory output and so leads to Huntington’s disease. At present there is no cure for this disease and trials are going on to treat symptoms, slow the progress of the disease and repairing the damages caused by disease. So there is a necessity to produce an animal model of HD by using a neurotoxin kainic acid for research purpose. By this study we produced a simple and effective rat model of HD which is more mimicking the human model of HD. We also analyzed the role of the extract of a herbal plant Withania somnifera and its active principle withanolide A in preventing the nervous system of HD rat models. Results: The activity of the herbal drug was analyzed by using rotarod apparatus. Both the drug group animals behaved normally in the rotarod against the lesion control animals and proved the efficacy of the drug employed. Conclusion: Present days treatments are mostly given to reduce the progress of HD and to treat the symptoms. Complete curation of HD is not up to the mark. But by taking these herbal drugs by daily basis we can prevent the occurrence of HD as these drugs are very good in neuroprotection.

Phytochemical and Antidepressant Activities of Selaginella Bryopteris (L.) Baker on Albino Mice.

Selaginella bryopteris is a pteridophytic plant belongs to the family selaginellaceae. Its familiar name is sanjeevani booti. The present study emphasized on phytochemical screening and antidepressant activity of Selaginella bryopteris on Albino mice. Phytochemical analysis was carried with a view to asses the therapeutic values and safty of plant in ethnomedicine. The results of the phytochemical screening shows the presence of alkaloids, flavonoids, phenols, tannins and results of the quantitative estimations revealed that maximum amount of alkaloids are present in methanolic extract when compared to flavonoids, phenols and tannins. From the results of the phytochemical estimations methanolic extract is found to be efficient. The antidepressant activity of Selaginella bryopteris was tested on mice by Hole board test and Rotarod test. In both the tests Diazepam (depressant/ for inducing depressant) is used as standard. The results of the Hole board test showed significant motar performance (head dipping behavior) with the dose of 250mg/kg (48.66±4.05 at 120min) and 500mg/kg ( 69.33±6.36 at 120min) compared to standard of 10mg/kg (1.66±1.20 at 120min) and it was very interesting to note that retention time of mice has been significantly improved in Rotarod test with the dose of 250mg/kg (3.96±0.35) and 500mg/kg (7.23±0.46) of the methanolic extract of Selaginella bryopteris.

Diet rich in date palm fruits improves memory, learning and reduces beta amyloid in transgenic mouse model of Alzheimer’s disease.

Background: At present, the treatment options available to delay the onset or slow down the progression of Alzheimer’s disease (AD) are not effective. Recent studies have suggested that diet and lifestyle factors may represent protective strategies to minimize the risk of developing AD. Date palm fruits are a good source of dietary fiber and are rich in total phenolics and natural antioxidants, such as anthocyanins, ferulic acid, protocatechuic acid and caffeic acid. These polyphenolic compounds have been shown to be neuroprotective in different model systems. Objective: We investigated whether dietary supplementation with 2% and 4% date palm fruits (grown in Oman) could reduce cognitive and behavioral deficits in a transgenic mouse model for AD (amyloid precursor protein [APPsw]/Tg2576). Materials and Methods: The experimental groups of APP‑transgenic mice from the age of 4 months were fed custom‑mix diets (pellets) containing 2% and 4% date fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety‑related behavior in all the animals at the age of 4 months and after 14 months of treatment using the Morris water maze test, rota‑rod test, elevated plus maze test, and open‑field test. We have also analyzed the levels of amyloid beta (Aβ) protein (1–40 and 1–42) in plasma of control and experimental animals. Results: Standard diet‑fed Tg mice showed significant memory deficits, increased anxiety‑related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination when compared to wild‑type on the same diet and Tg mice fed 2% and 4% date supplementation at the age of 18 months. The levels of both Aβ proteins were significantly lowered in date fruits supplemented groups than the Tg mice without the diet supplement. The neuroprotective effect offered by 4% date fruits diet to AD mice is higher than 2% date fruits diet. Conclusions: Our results suggest that date fruits dietary supplementation may have beneficial effects in lowering the risk, delaying the onset or slowing down the progression of AD.

Enhancement of Short-Term Memory by Methyl-6-(Phenylethynyl)-Pyridine in the BTBR T+tf/J Mouse Model of Autism Spectrum Disorder

BACKGROUND: Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors. This study evaluated the effect of methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, on memory enhancement in the BTBR T+tf/J (BTBR) mouse strain, which has been recognized as a model of ASD. METHODS: The pharmacological effects of MPEP on memory and motor coordination were assessed using the Morris water maze and rotarod tests in BTBR and C57BL/6J (B6) mice. Furthermore, we performed morphological analyses of cerebellar foliation in BTBR and B6 mice using hematoxylin and eosin staining. RESULTS: MPEP-treated BTBR mice exhibited improved learning and memory in the Morris water maze test. MPEP administration also improved motor coordination in the rotarod test. However, no significant difference was observed regarding the numbers of Purkinje cells in the cerebella of BTBR versus normal B6 mice. CONCLUSION: This study suggests that the mGluR5 antagonist MPEP has the potential to ameliorate learning and memory dysfunction and impaired motor coordination in BTBR mice. These results further suggest that the BTBR mouse model may be useful in pharmacological studies investigating drugs that could potentially alleviate cognitive dysfunction in ASD.

Effect of benzene on the cerebellar structure and behavioral characteristics in rats

Objective:To investigate the effects of benzene on rat’s cerebellum structure and behavioral characteristics, including anxiety and motor impairment. Methods:Twenty rats were randomly allocated into two groups orally receiving distilled water and benzene (200 mg/kg/day). A total of 10 rats were used at the beginning of benzene exposure. Two rats died during benzene treatment and 8 rats remained for evaluation of the behavioral test and finally 6 rats underwent histological assessment. At the end of the 4th week, motor function and anxiety were evaluated in rotarod test and elevated plus maze, respectively. Besides, the cerebellum was dissected for structural assessment using stereological methods. Results:Performance of the benzene-treated rats in fixed and accelerating speed rotarod was impaired and their riding time (endurance) was lower compared to the control group (P=0.02). The benzene-treated rats also spent less time in the open arms and had fewer entrances to the open arms in comparison to the control group, indicating anxiety (P=0.01). The total volume of the cerebellar hemisphere, its cortex, intracerebellar nuclei, total number of the Purkinje, Bergmann, Golgi, granule, neurons and glial cells of the molecular layer, and neurons and glial cells of the intracerebellar nuclei were reduced by 34%-76%in the benzene-treated rats in comparison to the distilled water group (P=0.003). The most cell loss was seen in Bergmann glia. Conclusions:The structure of cerebellum altered after benzene treatment. In addition, motor impairment and anxiety could be seen in benzene-treated rats.

Effect of benzene on the cerebellar structure and behavioral characteristics in rats

Objective: To investigate the effects of benzene on rat's cerebellum structure and behavioral characteristics, including anxiety and motor impairment. Methods: Twenty rats were randomly allocated into two groups orally receiving distilled water and benzene (200 mg/kg/day). A total of 10 rats were used at the beginning of benzene exposure. Two rats died during benzene treatment and 8 rats remained for evaluation of the behavioral test and finally 6 rats underwent histological assessment. At the end of the 4th week, motor function and anxiety were evaluated in rotarod test and elevated plus maze, respectively. Besides, the cerebellum was dissected for structural assessment using stereological methods. Results: Performance of the benzene-treated rats in fixed and accelerating speed rotarod was impaired and their riding time (endurance) was lower compared to the control group (P = 0.02). The benzene-treated rats also spent less time in the open arms and had fewer entrances to the open arms in comparison to the control group, indicating anxiety (P = 0.01). The total volume of the cerebellar hemisphere, its cortex, intracerebellar nuclei, total number of the Purkinje, Bergmann, Golgi, granule, neurons and glial cells of the molecular layer, and neurons and glial cells of the intracerebellar nuclei were reduced by 34%-76% in the benzene-treated rats in comparison to the distilled water group (P = 0.003). The most cell loss was seen in Bergmann glia. Conclusions: The structure of cerebellum altered after benzene treatment. In addition, motor impairment and anxiety could be seen in benzene-treated rats.

Evaluation of Abelmoschus moschatus seed extract in psychiatric and neurological disorders.

Background: Abelmoschus moschatus is an aromatic and medicinal plant, used as traditional medicine in the Thirunelveli district and distributed in many parts of Asia, including India. The present study was aimed to evaluate central nervous system (CNS) activities of ethanolic seed extract of A. moschatus (AEAM). Methods: Oral administration of AEAM at doses of 200 and 400 mg/kg on various behavioral models forced swim, tail suspension, light-dark box, hole-board, elevated-plus-maze, locomotor, strychnine, maximal electroshock induced seizure, pentylenetetrazole (PTZ), rotarod, climbing an inclined screen models were utilized. Results: In the open field test, AEAM (200 and 400 mg/kg) increased the numbers of rearing. However, the number of central motor and ambulation were reduced. The number of entries and the time spent in the open arm were increased, whereas the number of locomotion was decreased (p<0.001) in elevated-plus-maze and actophotometer test, respectively. AEAM (200 and 400 mg/kg) protected the mice against the PTZ and strychnine-induced convulsions; it causes significant dose-dependent increase in latency of convulsion. Treatment with AEAM reduced the duration of the tonic hind limb extension, increased the hypnotics time and decreased motor co-ordination of experimental animals. Conclusion: This study concludes A. moschatus is an alternative source for CNS drug development.

Evaluation of central nervous system activities of Citrus maxima leaf extract on rodents.

Citrus maxima is a traditional medicine used to treat astringent, constipation, hypnotic, inflammation and antiseptic. Therefore, we aimed to evaluate central nervous system activities of ethanolic extract of Citrus maxima (EECM). Oral administration of 200 and 400 mg/kg of EECM was to the depressant, anxiolytic, convulsant, hypnotic and muscle relaxant experimental animals. In the locomotor test, EECM increased the numbers of rearing, central motor and ambulation were reduced. The number of entries and time spent in the open arm was increased, decreased locomotion in elevated-plus-maze and actophotometer test. EECM protected the mice against the pentylenetetrazole and strychnine induced convulsion in a dose dependent manner. Treatment with EECM (p<0.01) reduced the duration of the tonic hind limb extension, increased hypnotics time and decreased motor co-ordination of experimental animals. This study concludes C. maxima will be an alternative source for psychiatric and neurological disorders.

Aluminum and ethanol induce alterations in superoxide and peroxide handling capacity (SPHC) in frontal and temporal cortex.

Aluminum is an omnipresent neurotoxicant and has been associated with several neuropathological disorders. Cerebrum and cerebellum have been shown to face augmented oxidative stress when animals are exposed to aluminum and high doses of ethanol. To establish the link between oxidative stress and neurobehavioral alterations, the present study was conducted to determine the extent of oxidative stress in low levels of pro-oxidant (ethanol exposure) status of the functionally discrete regions of the cerebrum. Male Wistar rats were exposed to aluminum (10 mg/kg body wt) and ethanol (0.2-0.6 g/kg body wt) for 4 weeks. Spontaneous motor activity (SMA) and Rota-Rod performances (RRP) were recorded weekly during the period of exposure. At the end of 4th week, oxidative stress parameters were determined from the homogenized cerebral tissue. GSH-independent superoxide peroxide handling capacity (GI-SPHC) and GSH-dependent superoxide peroxide handling capacity (GD-SPHC) were determined for FC and TC upon exposure to ethanol in the absence and presence of aluminum exposure. Aluminum was found to augment the oxidative stress at higher doses (0.6 g Ethanol/kg body wt) of ethanol, particularly in FC. The SPHC of FC was also found to be compromised significantly in aluminum-ethanol co-exposed animals. It was concluded that even though the manifestation of oxidative stress was not observed as revealed by assaying the widely used oxidative stress biochemical markers (indices), aluminum and ethanol (low doses) exposure induced alterations in the handling capacity of oxidant imbalance that could be recognized by studying the SPHC of FC. Comparison of GD-SPHC and GI-SPHC offered a possible mechanism of compromised SPHC in FC. This observation is likely to offer insights into the mechanism of association between aluminium exposure and behavioral changes in neurodegenerative disorders towards therapeutic strategies for these disorders.

Differential gene expression pattern in brains of acrylamide-administered mice / 대한수의학회지

The present study was performed to evaluate the relationship between the neurotoxicity of acrylamide and the differential gene expression pattern in mice. Both locomotor test and rota-rod test showed that the group treated with higher than 30 mg/kg/day of acrylamide caused impaired motor activity in mice. Based on cDNA microarray analysis of mouse brain, myelin basic protein gene, kinesin family member 5B gene, and fibroblast growth factor (FGF) 1 and its receptor genes were down-regulated by acrylamide. The genes are known to be essential for neurofilament synthesis, axonal transport, and neuro-protection, respectively. Interestingly, both FGF 1 and its receptor genes were down-regulated. Genes involved in nucleic acid binding such as AU RNA binding protein/enoyl-coA hydratase, translation initiation factor (TIF) 2 alpha kinase 4, activating transcription factor 2, and U2AF 1 related sequence 1 genes were down-regulated. More interesting finding was that genes of both catalytic and regulatory subunit of protein phosphatases which are important for signal transduction pathways were down-regulated. Here, we propose that acrylamide induces neurotoxicity by regulation of genes associated with neurofilament synthesis, axonal transport, neuro-protection, and signal transduction pathways.

Potential of Pandanus odoratissimus as a CNS depressant in Swiss albino mice / Potencial de Pandanus odoratissimus como um depressor do sistema nervoso central em camundongos Swiss albinos

In this study, several neuropharmacological effects of methanolic leaf extract of Pandanus odoratissimus (PO) (family; Pandanaceae) were studied in albino mice using various experimental models. The effect of PO on the CNS was studied by using different neuropharmacological paradigms including spontaneous motor activity, rota-rod performance and potentiation of Pentobarbital sodium sleeping time in albino mice. Preliminary phytochemical evaluation and acute toxicity studies were also carried out where LD50 >2000 mg/kg was considered non-toxic through acute exposure in rats by the oral route. The methanolic leaf extract (50,100 and 200 mg/kg i. p.) produced a reduction in spontaneous motor activity, motor coordination and prolonged Pentobarbital sodium sleeping time. Preliminary qualitative chemical studies indicated the presence of steroids, saponins, terpinoids, glycosides, tannins, flavonoids and phenolics in the extract. These observations suggest that the leaf of Pandanus odoratissimus contains some active principles which possess potential CNS-depressant action.

Estudaram-se alguns efeitos neurofarmacológicos do extrato metanólico de Pandanus odoratissimus (PO) (família Pandanaceae) em camundongos albinos, usando vários modelos experimentais. O efeito do PO no SNC foi estudado por meio de diferentes paradigmas neurofarmacológicos, como atividade motora espontânea, desempenho na haste rotatória e a potenciação do tempo de sono em camundongos albinos pelo pentobarbital sódico. A avaliação fitoquímica preliminar e os estudos de toxicidade aguda foram realizados e a DL50 >2000 mg/kg é considerada não tóxica, por meio da exposição aguda, por via oral, em ratos. O extrato metanólico de folha (50,100 e 200 mg/kg i. p.) produziu redução da atividade motora espontânea, da coordenação motora e tempo prolongado de sono pelo pentobarbital sódico. Estudos químicos qualitativos preliminares indicaram a presença de esteróide, saponinas, terpenóides, glicosídios, taninos, flavonóides e fenólicos no extrato. As observações sugerem que a folha de Pandanus odoratissimus contém alguns princípios ativos com atividade potencial como depressores do SNC.

Behavioral effects of aqueous and dichloromethane extracts of Erythrina speciosa Andrews, Fabaceae, leaves in mice / Efeitos comportamentais do extrato aquoso bruto e fração diclorometano das folhas de Erythrina speciosa Andrews, Fabaceae, em camundongos

Erythrina speciosa Andrews, Fabaceae, is used in the South of Brazil as sedative and tranquilizers. In this study, behavioral effects of aqueous (AE) and dichloromethane (DCM) extracts of E. speciosa leaves were evaluated in male mice, as well as their lethal dose 50 percent (LD50). The extracts were administered by gavage in doses ranging from 50 to 400 mg/kg 1 h before the behavioral tests. AE decreased ambulation (50, 100 and 400 mg/kg) and rearing (50 and 400 mg/kg) in the open-field but did not influence elevated plus maze, rotarod and pentobarbital-induced sleep tests. No behavioral effects were observed after DCM administration. LD50 for both extracts were higher than 2000 mg/kg. The results showed that AE and DCM extracts of E. speciosa leaves do not produce anxiolytic effect in the elevated plus maze nor seems to depress the Central Nervous System. However, since serotonergic mechanisms may be involved in the pharmacological action of Erythrina plants and the elevated plus maze test is not adequate to evaluate serotonergic drugs, our results do not invalidate the use of this plant in folk medicine but suggest that the mechanism involved in a possible central action of Erythrina needs to be clarified.

Erythrina speciosa Andrews, Fabaceae, é usada na região Sul do Brasil como sedativa e tranquilizante. Neste estudo, uma possível ação central do extrato aquoso (EA) e fração diclorometano (DCM) das folhas da E. speciosa foi avaliada em camundongos machos submetidos a testes comportamentais 1 h após o tratamento (gavage). Também foi avaliada a dose letal 50 por cento (DL50) como indicativa da toxicidade aguda desta planta. O EA diminuiu a locomoção (50, 100 e 400 mg/kg) e o levantar (50 e 400 mg/kg) no teste de campo aberto mas não alterou nenhum dos comportamentos avaliados nos testes de labirinto em cruz elevado, rotarod e sono induzido. A DCM não alterou nenhum dos comportamentos avaliados. A DL50 de ambos os extratos foi estimada como sendo >2000 mg/kg. Os resultados sugerem ausência de efeito ansiolítico e depressor do Sistema Nervoso Central das folhas de E. speciosa. Entretanto, como mecanismos serotonérgicos podem estar envolvidos na ação farmacológica de plantas do gênero Erythrina e o teste de labirinto em cruz elevado não é adequado para avaliar o efeito de drogas serotonérgicas, nossos resultados não invalidam o uso desta planta na medicina popular, mas apontam a necessidade de se investigar o mecanismo de ação envolvido no possível efeito central de plantas do gênero Erythrina.

Efeitos da hipóxia-isquemia perinatal sobre o comportamento motor, distribuição da Tirosina Hidroxilase na substância negra e da NADPH diaforase no hipocampo durante o desenvolvimento em ratos / Effects of hypoxia-ischemia under motor behavior, tyrosine hydroxylase distribution in the nigra substantia and the diaphorase NADPH in hippocampus in rats

A hipóxia isquemia (HI) pré-natal é uma das principais causas de mortalidade e doenças neurológicas crônicas em neonatos, que podem apresentar déficits remanentes como: retardamento, paralisia cerebral, dificuldade de aprendizado ou epilepsia. Estes prejuízos, provavelmente, estão relacionados com o atraso no desenvolvimento neural, astrogliose e com a perda de neurônios e oligodendrócitos. Déficits funcionais e cognitivos estão associados à degeneração de vias dopaminérgicas e de estruturas hipocampais. A enzima tirosina hidroxilase (TH) é a enzima limitante na síntese de dopamina e seus níveis são alterados em eventos de HI. O óxido nítrico (NO) é um gás difusível que atua modulando diferentes sistemas, participando de eventos como plasticidade sináptica e neuromodulação no sistema nervoso central e é produzido em grandes quantidades em eventos de injúria e inflamação, como é o caso da HI. O presente estudo teve por objetivos avaliar, utilizando o modelo criado por Robinson e colaboradores em 2005, os efeitos da HI sobre o comportamento motor e avaliar o desenvolvimento de estruturas encefálicas relacionadas a este comportamento como a substância negra (SN) e o complexo hipocampal. A HI foi induzida a partir do clampeamento das artérias uterinas da rata grávida, por 45 minutos no décimo oitavo dia de gestação (grupo HI). Em um grupo de fêmeas a cirurgia foi realizada, mas não houve clampeamento das artérias (grupo SHAM). A avaliação do comportamento motor foi realizada com os testes ROTAROD e de campo aberto em animais de 45 dias. Os encéfalos foram processados histologicamente nas idades de P9, P16, P23 e P90, sendo então realizada imunohistoquímica para TH e histoquímica para NADPH diaforase (NADPH-d), para avaliação do NO. Nossos resultados demonstraram redução da imunorreatividade para a TH em corpos celulares na SN aos 16 dias no grupo HI e aumento na imunorreatividade das fibras na parte reticulada aos 23 dias, com a presença de corpos celulares...

Perinatal hypoxia-ischemia (HI) is one of the major causes of mortality and chronic neurological diseases in newborns that can show permanent effects such as mental retardation, cerebral palsy, learning difficulty and epilepsy. It is probable that these impairs may be related to a delay in the neural development, astrogliosis and to the death of neurons and oligodendrocytes. Cognitive and functional deficits are related to degeneration of dopaminergic pathways and hippocampus. The enzyme tyrosine hydroxylase (TH) is a limiting step in the dopamine synthesis and its levels are impaired in HI insults. Nitric oxide (NO) is a diffusible gas that acts by modulating different systems and participates in several phenomena such as synaptic plasticity and neuromodulation in the central nervous system and is produced in higher levels in events of injury and inflamation as in the case of HI. This study aimed to evaluate the effects of HI on the motor behavior and to evaluate the development of brain structures related to this behavior as the substantia nigra (SN) and the hippocampal complex, using the model developed by Robinson and colleagues in 2005. HI was induced by clamping the uterine arteries of pregnant rats, for 45 minutes, on the eighteenth day of gestation (group HI). In a group of females, the surgery was performed, but no clamping of the arteries (group SHAM) was made. Assessment of motor behavior was performed with the ROTAROD test and open field test in animals of 45 days (P45) of age. The brains were processed histologically at ages P9, P16, P23 and P90, and then submitted to immunohistochemistry for TH and NADPH diaphorase (NADPH-d) histochemistry for evaluation of NOS. Our results demonstrated an apparent decrease in TH immunoreactivity in cell bodies in the SN at P16 in the HI group and an increase in immunoreactivity of the fibers in the SN pars reticulata at P23 with the presence of TH immunoreactive cell bodies at this same region in the HI group...