Distribution of calcitonin gene-related peptide and vascular endothelial growth factor in the mouse lung at the embryonic and postnatal stages / Distribución del péptido relacionado con el gen de la calcitonina y el factor de crecimiento endotelial vascular en el pulmón de ratón en las etapas embrionaria y posnatal

SUMMARY: Neuropeptide calcitonin gene-related peptide (CGRP) is a neurotransmitter related to vasculogenesis during organ development. The vascular endothelial growth factor A (VEGF-A) is also required for vascular patterning during lung morphogenesis. CGRP is primarily found in organs and initially appears in pulmonary neuroendocrine cells during the early embryonic stage of lung development. However, the relationship between CGRP and VEGF-A during lung formation remains unclear. This study investigates CGRP and VEGF-A mRNA expressions in the embryonic, pseudoglandular, canalicular, saccular, and alveolar stages of lung development from embryonic day 12.5 (E12.5) to postnatal day 5 (P5) through quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Further, we analyzed the expression of CGRP via immunohistochemistry. The VEGF-A mRNA was mainly scattered across the whole lung body from E12.5. CGRP was found to be expressed in a few epithelial cells of the canalicular and the respiratory bronchiole of the lung from E12.5 to P5. An antisense probe for CGRP mRNA was strongly detected in the lung from E14.5 to E17.5. Endogenous CGRP may regulate the development of the embryonic alveoli from E14.5 to E17.5 in a temporal manner.

El péptido relacionado con el gen de la calcitonina (CGRP) es un neurotransmisor vinculado con la vasculogénesis durante el desarrollo de órganos. El factor de crecimiento endotelial vascular A (VEGF-A) también se requiere para el patrón vascular durante la morfogénesis pulmonar. El CGRP se encuentra principalmente en los órganos y aparece inicialmente en las células neuroendocrinas pulmonares durante la etapa embrionaria temprana del desarrollo pulmonar. Sin embargo, la relación entre CGRP y VEGF-A durante la formación de los pulmones sigue sin estar clara. Este estudio investiga las expresiones de ARNm de CGRP y VEGF-A en las etapas embrionaria, pseudoglandular, canalicular, sacular y alveolar del desarrollo pulmonar desde el día embrionario 12,5 (E12,5) hasta el día postnatal 5 (P5) a través de la reacción en cadena de la polimerasa cuantitativa en tiempo real. (qRT-PCR) e hibridación in situ. Además, analizamos la expresión de CGRP mediante inmunohistoquímica. El ARNm de VEGF-A se dispersó principalmente por todo parénquima pulmonar desde E12,5. Se encontró que CGRP se expresaba en unas pocas células epiteliales de los bronquiolos canaliculares y respiratorios del pulmón desde E12,5 a P5. Se detectó fuertemente una sonda antisentido para ARNm de CGRP en el pulmón de E14,5 a E17,5. El CGRP endógeno puede regular el desarrollo de los alvéolos embrionarios de E14,5 a E17,5 de manera temporal.

Review of traditional Chinese medicines in ameliorating neuropsychiatric diseases by improving the levels of monoamine neurotransmitters via gut microbiota regulation / 中国中药杂志

The degeneration of monoaminergic system and the reduction of monoamine neurotransmitters(MNTs) are associated with the occurrence of a variety of neuropsychiatric diseases, becoming the key indicators for clinical diagnosis and treatment. Recent studies suggested gut microbiota could influence the occurrence, development, and treatment of neuropsychiatric diseases by directly or indirectly regulating the synthesis and metabolism of MNTs. Rich clinical experience has been accumulated in the amelioration and treatment of neuropsychiatric diseases by traditional Chinese medicines. The traditional oral administration method demonstrates obvious advantages in regulating gut microbiota. It provides a new idea for explaining the pharmacodynamic material basis and mechanism of traditional Chinese medicines in ameliorating neuropsychiatric disease by improving the levels of MNTs via gut microbiota regulation. Focusing on three common neuropsychiatric diseases including Alzheimer's disease, Parkinson's disease, and major depression, we summarized the pathways of gut microbiota in regulating the levels of MNTs and the paradigms of traditional Chinese medicines in ameliorating neuropsychiatric diseases via the "bacteria-gut-brain axis", aiming to provide ideas for the development of drugs and treatment schemes.

Effects of umbilical moxibustion on phobic behavior and monoamine neurotransmitters in stress-model rats / 中国针灸

OBJECTIVE@#To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior.@*METHODS@#Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined.@*RESULTS@#Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group.@*CONCLUSION@#Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.

Hippocampus: Molecular, Cellular, and Circuit Features in Anxiety / 神经科学通报·英文版

Anxiety disorders are currently a major psychiatric and social problem, the mechanisms of which have been only partially elucidated. The hippocampus serves as a major target of stress mediators and is closely related to anxiety modulation. Yet so far, its complex anatomy has been a challenge for research on the mechanisms of anxiety regulation. Recent advances in imaging, virus tracking, and optogenetics/chemogenetics have permitted elucidation of the activity, connectivity, and function of specific cell types within the hippocampus and its connected brain regions, providing mechanistic insights into the elaborate organization of the hippocampal circuitry underlying anxiety. Studies of hippocampal neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, dopaminergic, and serotonergic systems, have contributed to the interpretation of the underlying neural mechanisms of anxiety. Neuropeptides and neuroinflammatory factors are also involved in anxiety modulation. This review comprehensively summarizes the hippocampal mechanisms associated with anxiety modulation, based on molecular, cellular, and circuit properties, to provide tailored targets for future anxiety treatment.

Experiencia de la neuromodulación en un hospital de alta complejidad / High Complexity Hospital ́s experience in neuromodulation

La neuromodulación es una práctica médica implementada desde hace más de cuatro décadas. En lo que respecta a la Neurocirugía, cumple un papel en el tratamiento de diversas patologías (Parkinson, distonías, epilepsia, etc.) y con un gran potencial para aplicarlas en otras (trastorno obsesivo compulsivo [TOC], dolor pélvico). Es por ello que, en los últimos años, se cuadruplicaron las inversiones de empresas biotecnológicas en este campo por la demanda y aplicación de la terapia. La neuromodulación abarca también otras especialidades, como por ejemplo Otorrinolaringología (ORL) en implantes cocleares, Cardiología con diversos modelos de marcapasos cardíacos, Endocrinología con bombas de infusión de medicamentos, Uroginecología en incontinencia, etcétera. Nuestra institución aplica en su práctica clínica todas estas técnicas, y cumple una función jerárquica como centro de referencia en educación y políticas sanitarias. Por estos aspectos, sumados a su infraestructura, personal profesional y enfoque sanitario, puede ser considerada como un Centro de Neuromodulación referente en la región. (AU)

Neuromodulation is a medical practice established for more than forty years. In the neurosurgical field it plays a role in the treatment of different diseases (Parkinson, Dystonia, Epilepsy, etc) and has a great potential to apply in other pathologies (Obsessive Compulsive Disorder, Pelvic pain). In the last years the biotechnological industry has quadrupled the investment in this field because of the demand and therapy application. Neuromodulation encompasses other specialities, for example otorhinolaryngology in cochlear implants, in cardiology with different models of pacemakers, endocrinology with implanted infusion pumps, urological gynecology in incontinence treatments, etc. Our institution applies all these techniques in its clinical practice, having a hierarchical role as a reference center in education and health policies. Due to these aspects, added to its infrastructure, professional staff and health approach, it can be considered as a reference Neuromodulation Center in the region. (AU)

La depresión con ideas suicidas presenta disfunciones corticales prefrontales que favorecen significativamente el intento suicida / Depression with suicidal ideas presents prefrontal cortical dysfunctions that significantly favor suicidal intent

Se realiza una revisión de estudios de resonancia magnética integral y funcional, así como estudios bioquímicos en pacientes con y sin ideas suicidas. Estos estudios en pacientes con alto riesgo de suicidio presentan una disminución de volúmenes corticales en la corteza prefrontal dorso y ventrolateral. Lo importante de estos estudios es que resultan de la comparación con pacientes deprimidos con bajo riesgo de suicidio. Los estudios de resonancia magnética funcional mostraron una hipofuncionalidad del lóbulo prefrontal en los pacientes depresivos con ideas suicidas severas, que se observa como una disminución del flujo sanguíneo cerebral en las áreas lateral y ventral. Se observa una disminución del metabolismo de serotonina, en clara relación con la severidad de las ideas de muerte, también con un foco en la región lateroventral prefrontal. Dado que las funciones de la corteza prefrontal afirman al individuo en su perspectiva vital, disfunciones como las descritas debilitan la coordinación y organización del apego a la vida, quedando, por el contrario, la posibilidad de la búsqueda de la muerte. Se concluye que los pacientes depresivos con ideas suicidas tienen una alta vulnerabilidad para el intento de suicidio por la afectación de las zonas prefrontales.

A review of functional integral magnetic resonance and biochemical data from patients with and without suicidal ideation is presented. Patients with high suicidal risk show a decrease in cortical volume in ventrolateral and dorsal prefrontal cortex. These studies are compared to those of depressed patients with low suicidal risk. Functional magnetic resonance in depressed patients with severe suicidal ideation show an hypo functional prefrontal lobe, seen as a decrease in blood flow in lateral and ventral areas. There is a decrease in serotonin metabolism, clearly related to the severity of suicidal ideation, also in ventrolateral prefrontal cortex. As prefrontal cortex functions enhance vital perspectives, such dysfunctions weaken coordination and organization of attachment to life, making search for death a possibility. Authors conclude that depressed patients with suicidal ideation have a high vulnerability for suicidal intent due to changes in prefrontal areas.

Effects of early life PM2.5 exposure on prefrontal cortex of offspring male rats / 中国应用生理学杂志

Objective: To investigate the effects of PM2.5 exposure at different stages of early life on the prefrontal cortex of offspring rats. Methods: Twelve pregnant SD rats were randomly divided into four groups: Control group (CG), Maternal pregnancy exposure group (MG), Early postnatal exposure group (EP) and Perinatal period exposure group (PP), 3 rats in each group. The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM2.5. MG was exposed from gestational day (GD) 1 to GD21. EP was exposed from postnatal day (PND) 1 to PND21, and PP was exposed from GD1 to PND21. After exposure, the prefrontal cortex of 6 offspring rats in each group was analyzed. HE staining was used to observe the pathological damage in the prefrontal cortex. ELISA was employed to detect neuroinflammatory factors, and HPLC/MSC was applied to determine neurotransmitter content. Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers, respectively. Results: Compared with MG and CG, the pathological changes of prefrontal cortex in PP and EP were more obvious. Compared with MG and CG, the neuroinflammatory factors (IL-1, IL-6, TNF-α) in PP and EP were increased significantly (P＜0.01), the level of MT were decreased significantly (P＜0.05), and the level of oxytocin (OT) showed a downward trend; the level of neurotransmitter ACh was also increased significantly (P＜0.01). Compared with MG and CG, the GFAP level of PP and EP showed an upward trend, the level of oxidative stress index SOD in PP and EP was decreased significantly (P＜0.01), and the level of ROS was increased significantly (P＜0.01). Compared with the offspring rats of CG and MG, the CAT level of PP was decreased significantly (P＜0.01, P＜0.05). Compared with the offspring rats of CG, the CAT level of EP was decreased significantly (P＜0.05). There was no significant difference in IL-1, IL-6, TNF-α, MT, OT, ACh, GFAP, SOD, ROS and CAT levels between PP and EP, or MG and CG. Conclusion: PM2.5 exposure in early life has adverse effects on the prefrontal cortex of offspring male rats, and early birth exposure may be more sensitive.

Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter / 中国结合医学杂志

OBJECTIVE@#To investigate the therapeutic effect of Yixin Ningshen Tablet (YXNS) on comorbidity of myocardial infarction (MI) and depression in rats and explore the underlying mechanism.@*METHODS@#The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights, including control, model, fluoxetine (FLXT, 10 mg/kg), low-dose YXNS (LYXNS, 100 mg/kg), and high-dose YXNS (HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction (MI) area and myocardial apoptosis was also detected. Serum levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), adrenocorticotrophic hormone (ACTH), corticosterone (CORT), and norepinephrine (NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5'-monophosphate -activated protein kinase (AMPK), p-AMPK, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase (IDO1), kynurenine 3-monooxygenase (KMO), and kynureninase (KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction.@*RESULTS@#Compared with the model group, the cardiac function of rats treated with YXNS improved significantly (P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats (P<0.01 or P<0.05), promoted AMPK phosphorylation, and increased PGC-1α protein expression (P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH, and CORT (all P<0.05). Moreover, HYXNS decreased the mRNA expressions of IDO1, KMO and KYNU (P<0.05).@*CONCLUSIONS@#YXNS can relieve MI by enhancing myocardial energy metabolism. Meanwhile, YXNS can alleviate depression by resisting inflammation and increasing availability of monoamine neurotransmitters. It may be used as a potential drug to treat comorbidity of MI and depression.

Viés da Escalada, Daemons de Otimização, e a Influência da Narrativa Social Aceleracionista / Hill-Climbing Bias, Optimization Daemons, and the Influence of Accelerated Social Narratives

O fenômeno de aceleração social, intimamente ligado a nossa modernização tecnológica e os sistemas políticos e sociais que adotamos, vem sendo alvo de questionamentos por parte da teoria crítica por diversos filósofos e sociólogos, principalmente em relação a se tal "aceleração" seja algo que, possa ser justificável pelo bem comum da sociedade. De fato, as rápidas mudanças que ocorreram no último século causaram uma tremenda mudança em nossos estilos-de-vida, e na maneira como experienciamos o mundo. Que a nossa sociedade mudou e continua a mudar é um fato evidente quando olhamos criticamente para o passado e presente, e comparamos diferentes épocas da história humana. Neste ensaio tentaremos explorar algumas possíveis hipóteses que fundamentem o comportamento aceleracionista em certos fatores e mecanismo biológicos que caracterizam os sistemas de motivação e saciação humanos. Também tentaremos mostrar como certos fenômenos sociais podem auxiliar em fortalecer este tipo de comportamento, e suas possíveis origens evolutivas. Este estudo tem como objetivo principal fundamentar a Tese Aceleracionista em evidências neurofisiológicas, cognitivo-comportamentais, evolutivas e sociais.

The phenomenon of social acceleration is closely linked to our technological modernization and the political and social systems we have adopted, and it has been questioned by several philosophers and sociologists, especially in relation to whether such acceleration is something that can be justified for the common good of society. In fact, the rapid changes that have occurred in the last century have caused a tremendous change in our lifestyles, and in the way we experience the world. That society have changed and continues to change is an evident fact when we look critically to the past and our present and compare different times in human history. In this essay we will try to explore some possible hypotheses that underpin accelerated behavior, in certain biological factors and mechanisms that characterize human motivation and satiation systems. We will also try to show how certain social phenomena can help to strengthen this type of behavior, and its possible evolutionary origins. The main objective of this study is to base the Accelerationist Thesis on neurophysiological, cognitive-behavioral, evolutionary and also social evidence.

Estimulação elétrica transcraniana nos transtornos depressivos: determinação de parâmetros para a prática clínica / Effectiveness of transcranial electric stimulation in depressive disorders: parameters determination for clinical practice

A estimulação elétrica transcraniana (EET) é uma técnica de neuromodulação não invasiva, que tem sido utilizada como coadjuvante no tratamento de transtornos depressivos devido à sua capacidade de modificar a excitabilidade cortical. Objetivo: Analisar os efeitos da EET nos transtornos depressivos e propor parâmetros para a prática clínica. Métodos: Estudo de revisão sistemática no qual foram incluídos ensaios clínicos randomizados que utilizaram a EET no tratamento dos transtornos depressivos, publicados entre 2010 e junho de 2018, nas línguas inglesa e portuguesa. Resultados: Foram encontrados 14.775 estudos, sendo selecionados para a amostra apenas 15 trabalhos. Todos os estudos selecionados utilizaram a EET por corrente contínua e apresentaram semelhanças em relação aos demais parâmetros elétricos de tratamento e locais de aplicação dos eletrodos. Em 12 dos 15 estudos avaliados foi observada melhora significativa (p < 0,05) dos sintomas depressivos e, em relação aos efeitos adversos, constatou-se que são inferiores aos tratamentos convencionais. Conclusão: A EET apresenta eficácia no tratamento dos transtornos depressivos e que isto está diretamente relacionado ao uso adequado dos parâmetros e técnicas de aplicação da corrente elétrica. (AU)

Factores etiopatogénicos de las enfermedades autoinmunes en el siglo XXI / Etiopathogenic factors of autoimmune diseases in the 21st century

Introducción: La etiología de las enfermedades autoinmunes aún se desconoce, aunque se plantean diferentes causas. Objetivo: Describir el rol de factores como las hormonas, alimentación, estrés, enfermedades infecciosas y cáncer en las enfermedades autoinmunes. Métodos: Se realizó una revisión bibliográfica empleando Google Académico y artículos de libre acceso en la base de datos PubMed y SciELO, publicados entre enero del 2014 y junio del 2020. Se consultó la bibliografía nacional e internacional relevante y actualizada, con un total de 51 referencias, de estas, tres libros básicos de la especialidad de Inmunología y 48 artículos (12 en idioma español y 36 en inglés). Se utilizaron los términos de búsqueda según los descriptores del DeCS y MeSH. Resultados: Las hormonas femeninas incrementan el riesgo de las enfermedades autoinmunes. Un desbalance en la neurohormona melatonina puede generar linfocitos autorreactivos. El estrés puede mantener respuestas inflamatorias crónicas que causen daño tisular. Una adecuada alimentación permite que los comensales de la microbiota intestinal mantengan la homeostasis del sistema inmune. Las infecciones en ocasiones desarrollan respuestas autoinmunitarias. La causalidad entre el cáncer y la autoinmunidad es bidireccional producto de procesos inflamatorios. Conclusiones: Las enfermedades autoinmunes son más frecuentes en las mujeres. Una alimentación adecuada permite que la microbiota intestinal no se altere y que mantenga la homeostasis inmunológica. Situaciones de estrés e infecciones pueden iniciar respuestas autoinmunes. El cáncer puede favorecer el desarrollo de manifestaciones autoinmunes, y estas últimas por el predominio inflamatorio, favorecen la tumorogénesis(AU)

Introduction: The etiology of autoimmune diseases is still unknown, though several causes have been suggested. Objective: Describe the role of hormones, eating, stress, infectious diseases and cancer in immune diseases. Methods: A bibliographic review was conducted using Google Scholar and open access papers published in the databases Pubmed and SciELO from January 2014 to June 2020. Relevant updated national and international bibliography was consulted, for a total 51 references: three basic books from the specialty of immunology and 48 papers (12 in Spanish and 36 in English). The search terms used were obtained from the descriptors DeCS and MeSH. Results: Feminine hormones increase the risk of autoimmune diseases. Imbalance in the neurohormone melatonin may generate autoreactive lymphocytes. Stress may maintain chronic inflammatory responses causing tissue damage. Appropriate eating habits allow gut microbiota commensals to maintain the homeostasis of the immune system. Infections occasionally develop autoimmune responses. Causality between cancer and autoimmunity is bidirectional, due to the presence of inflammatory processes. Conclusions: Autoimmune diseases are more common among women. Appropriate eating habits prevent alterations of the gut microbiota, allowing it to maintain immune homeostasis. Stress situations and infections may trigger autoimmune responses. Cancer may foster the development of autoimmune manifestations, and these, due to the inflammatory predominance, may foster tumorigenesis(AU)

Receptores metabotrópicos de glutamato e sua relação com a Esclerose Lateral Amiotrófica (ELA) / Glutamate metabotropic receptors and its relationship with Amiotrophic Lateral Sclerosis (ALS)

A Esclerose Lateral Amiotrófica (ELA), uma doença neurodegenerativa fatal, que afeta neurônios motores superiores e inferiores, tem como fisiopatologia mais aceita a excitotoxicidade mediada por glutamato. O atual estudo tem como objetivo estabelecer a relação entre esse neurotransmissor e a ELA, a partir de uma revisão de literatura nas bases de dados Pubmed e Medline. O glutamato é o principal neurotransmissor do Sistema Nervoso Central (SNC) e a excitotoxicidade gerada pelo seu acúmulo nas fendas sinápticas é tida como um dos principais mecanismos envolvidos na fisiopatologia da ELA. Os indivíduos afetados pela ELA apresentam diminuição da expressão de determinados grupos de receptores metabotrópicos de glutamato (mGlu) nos neurônios e nas células da glia desses pacientes. Os mGlu possuem um papel de destaque na modulação da excitotoxicidade por glutamato e são subdivididos em três grupos. Os mGlus do grupo 1 amplificam as transmissões sinápticas excitatórias rápidas, e os dos grupos 2 e 3 atuam como neuroprotetores inibindo a liberação do glutamato na fenda sináptica. Os mGlus são, portanto, considerados alvos terapêuticos para a atuação de drogas que combatem a excitotoxicidade e induzem a produção de fatores neurotróficos, constituindo importante atuação no combate à ELA.

Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease that affects upper and lower motor neurons, has as the most accepted pathophysiology the glutamate-mediated excitotoxicity. The present study aims to establish the relationship between this neurotransmitter and ALS, based on a literature review in the PubMed and Medline databases. Glutamate is the main neurotransmitter of the central nervous system (CNS) and the excitotoxicity generated by its accumulation in the synaptic clefts is considered one of the main mechanisms involved in the pathophysiology of ALS. People affected by ALS present a decrease in expression of certain metabotropic glutamate receptor (mGlu) groups in neurons and glial cells of these patients. mGlu has a prominent role in modulating glutamate excitotoxicity and are subdivided into three groups. Group 1 mGlu amplifies rapid excitatory synaptic transmissions, while groups 2 and 3 act as neuroprotective agents, since among other functions they inhibit glutamate release into the synaptic cleft. Finally, mGlu are considered therapeutic targets for the action of drugs that fight excitotoxicity and induce the production of neurotrophic factors, constituting an important action in the fight against ALS.

Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro

Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of Phlogiellus bundokalbo venom against neurodegenerative diseases. Methods Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from Terebrio molitor larvae in vivo and fractions were screened for their inhibitory activities against AChE and BACE in vitro. Results The whole venom from P. bundokalbo demonstrated neuroactivity by inducing excitatory movements from T. molitor for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control. Conclusion The venom of P. bundokalbo contains compounds that demonstrate neuroactivity and anti-AChE activities in vitro, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.(AU)

Clinical effect and mechanism of / 中国针灸

OBJECTIVE@#To observe the effect of @*METHODS@#A total of 60 children with intellectual disability were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases dropped off). In the control group, rehabilitation training and routine acupuncture were adopted, 30 min each time, once a day, 6 times a week for 3 months. On the base of the treatment as the control group, @*RESULTS@#Compared before treatment, the scores of DQ and ADL and the serum levels of DA, NE, 5-HT after treatment were increased (@*CONCLUSION@#On the base of rehabilitation training and routine acupuncture,

Antidepressant effect of acidic polysaccharides from Poria and their regulation of neurotransmitters and NLRP3 pathway / 中国中药杂志

The rats were exposed to chronic unpredictable mild stress(CUMS) and kept in separate cages for inducing depressive disorder, which was judged by behavioral indicators. The number and morphology of neurons in hippocampal CA3 area and prefrontal cortex were observed by hematoxylin-eosin(HE) staining. The levels of brain-derived neurotrophic factor(BDNF), 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), norepinephrine(NE), glutamic acid(GLU), interleukin-1β(IL-1β), interleukin-18(IL-18), and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay(ELISA). Real-time polymerase chain reaction(RT-PCR) and Western blot were conducted to determine the mRNA and protein expression levels of related molecules in NLRP3 pathway. The results showed that compared with the model group, acidic polysaccharides from Poria at the low-, medium-, and high-doses(0.1, 0.3 and 0.5 g·kg~(-1)·d~(-1)) all improved the depression-like behavior of rats, increased the number of neurons and the levels of BDNF, 5-HT, 5-HIAA, DA, and NE in the hippocampus, and reduced GLU and serum IL-1β, IL-18, and TNF-α levels. The mRNA expression levels of ASC, caspase-1, IL-1β, and IL-18 and the protein expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in each medication group were down-regulated, whereas the protein expression levels of pro-caspase-1, pro-IL-1β, and pro-IL-18 were up-regulated. All these have indicated that acidic polysaccharides from Poria exerted the antidepressant effect possibly by regulating neurotransmitters and NLRP3 inflammasome signaling pathway.

Altered thalamic neurotransmitters metabolism and functional connectivity during the development of chronic constriction injury induced neuropathic pain

BACKGROUND: To investigate the thalamic neurotransmitters and functional connections in the development of chronic constriction injury (CCI)-induced neuropathic pain. METHODS: The paw withdrawal threshold was measured by mechanical stimulation the right hind paw with the von frey hair in the rats of CCI-induced neuropathic pain. The N-acetylaspartate (NAA) and Glutamate (Glu) in thalamus were detected by magnetic resonance spectrum (MRS) process. The thalamic functional connectivity with other brain regions was scanned by functional magnetic resonance image (fMRI). RESULTS: The paw withdrawal threshold of the ipsilateral side showed a noticeable decline during the pathological process. Increased concentrations of Glu and decreased levels of NAA in the thalamus were significantly correlated with mechanical allodynia in the neuropathic pain states. The thalamic regional homogeneity (ReHo) decreased during the process of neuropathic pain. The functional connectivity among the thalamus with the insula and somatosensory cortex were significantly increased at different time points (7, 14, 21 days) after CCI surgery. CONCLUSION: Our study suggests that dynamic changes in thalamic NAA and Glu levels contribute to the thalamic functional connection hyper-excitation during CCI-induced neuropathic pain. Enhanced thalamus-insula functional connection might have a significant effect on the occurrence of neuropathic pain.

Regression of dark color in subterranean fishes involves multiple mechanisms: response to hormones and neurotransmitters

Organisms with source-populations restricted to the subterranean biotope (troglobites) are excellent models for comparative evolutionary studies, due to their specialization to permanent absence of light. Eye and dark pigment regression are characteristics of most troglobites. In spite of the advance in knowledge on the mechanisms behind eye regression in cave fishes, very little is known about pigmentation changes. Studies were focused on three species of the genus Pimelodella. Exemplars of the troglobitic P. spelaea and P. kronei were compared with the epigean (surface) P. transitoria, putative sister-species of the latter. Melanophore areas and densities are significantly lower in the troglobitic species. Evaluating the in vitro response of these cells to adrenaline, acetylcholine and MCH, we observed a reduced response in both troglobites to adrenaline. The same trend was observed with MCH, but not statistically significant. No response to acetilcholine was detected in all the three. Contrary to expectations, even though eye-regression in P. spelaea was much lower than in P. kronei, pigmentation regression was more advanced. Multiple mechanisms of loss showing a mosaic of traits in troglobitic fishes are discussed here.(AU)

Organismos com populações-fonte restritas ao biótopo subterrâneo (troglóbios) são excelentes modelos para estudos evolutivos comparativos, devido à especialização resultante do isolamento sob um regime seletivo particular, com ênfase na permanente falta de luz. A regressão do olho e da pigmentação são características dos troglobites. Apesar do avanço do conhecimento sobre os mecanismos subjacentes à regressão ocular em peixes de caverna, pouco se sabe sobre mudanças de pigmentação. Os estudos foram focados em três espécies do gênero Pimelodella. Exemplares das espécies troglóbias P. spelaea e P. kronei foram comparados com a epígea P. transitoria, provável espécie-irmã dessa última. As áreas e densidades dos melanóforos são significativamente menores nas espécies troglóbias. Avaliando a resposta in vitro dessas células à adrenalina, acetilcolina e MCH, observamos uma resposta reduzida em ambos os troglóbios à adrenalina. A mesma tendência foi observado com o MCH, mas não estatisticamente. Nenhuma resposta à acetilcolina foi detectada três. Contrariamente às expectativas, embora a regressão ocular em P. spelaea seja bem menor do que em P. kronei, a regressão na pigmentação foi mais acentuada. Múltiplos mecanismos de regressão, mostrando um mosaico de características em peixes troglóbios, são discutidos aqui.(AU)

Regulatory effect of Jiaotai Pills on central and peripheral neurotransmitters in rats with heart-kidney imbalance insomnia / 中国中药杂志

To explore the pathogenesis of heart and kidney imbalance insomnia and the regulatory effect of Jiaotai Pills, in order to study the changes of central and peripheral neurotransmitters in rat. Insomnia rats with heart and kidney imbalance were induced through intraperitoneal injection with p-chlorophenylalanine(PCPA, 400 mg·kg~(-1)·d~(-1)), and the model rats were intragastrically administrated with Jiaotai Pills(3.3 g·kg~(-1)·d~(-1)) for 7 days. Nine neurotransmitters were determined by UPLC-MS/MS and principal component analysis(PCA) method in serum, urine, brain, heart, liver, kidney and adrenal gland of rats. The results showed that the ratio of 5-HT and 5-HIAA in platelet of insomnia rats was significantly lower than that in the normal group, and Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, the changed neurotransmitters in blood of insomnia rats were 5-HIAA, E, NE, DA, Glu and ACH, and except ACH, the changes of 7 kinds of neurotransmitters in urine were more significant, Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, all of the 8 neurotransmitters in insomnia rats except HVA were changed. Jiaotai Pills could regulate the neurotransmitters in each tissue of insomnia rats, especially in brain, liver and adrenal gland. In conclusion, insomnia is caused by not only a change of neurotransmitters in brain, but also a series of changes in peripheral tissues. It indicates that insomnia is a systematic imbalance of neurotransmitters. Jiaotai Pills not only regulates the central nervous system, but also has a certain protective effect on other organs, reflecting the multi-target and systematic effect of Jiaotai Pills in the treatment of insomnia.

Progress in fluorescent visualization techniques for neurotransmitter detection / 生物工程学报

Neurotransmitters play an important role in nervous system. Temporal and spatial changes of neurotransmitter distribution are crucial to information processing in neural networks. Biosensors that can visually monitor neurotransmitters are one of the vital tools to explore a variety of physiological and pathological activities. This article reviews recent advances in monitoring neurotransmitters with high temporal and spatial resolution, and introduces the latest fluorescent imaging methods for typical neurotransmitters, including glutamate, dopamine, γ-aminobutyric acid and acetylcholine. The article also summarizes the basic principles, advantages and disadvantages of various visually detection methods, and provides systematic suggestions for designing neurotransmitter sensors with high temporal and spatial resolution.