GABA Supplementation, Increased Heart-Rate Variability, Emotional Response, Sleep Efficiency and Reduced Depression in Sedentary Overweight Women Undergoing Physical Exercise: Placebo-Controlled, Randomized Clinical Trial.

Gamma-aminobutyric acid (GABA) serves as a pivotal neurotransmitter implicated in the pathogenesis of stress, anxiety, sleep-related disorders, and heart rate (HR) reactions. Heart-rate variability (HRV), modulated by the sympathetic and parasympathetic branches of the autonomic nervous system (ANS), offers insights into cardiac autonomic control and cardiovascular well-being. The present study aimed to explore the impact of GABA supplementation on emotional metrics, sleep quality, and HRV in sedentary women with overweight or obesity partaking in physical exercise. A randomized, double-blind, placebo-controlled clinical trial was undertaken involving 30 sedentary women with overweight or obesity. Volunteers were assigned randomly to two groups: the intervention group receiving GABA (200 mg) once daily for a total of 90 supplementation doses, and the placebo group. Both groups engaged in physical exercise, while the supplementation regimen spanned 90 days. Assessments were conducted at three intervals: baseline (T0), midway through the study (T45), and study culmination (T90). Following 90 days of GABA supplementation, the intervention group demonstrated enhancements in habitual sleep efficiency, as indicated by reductions in Pittsburgh Sleep Quality Index (PSQI) scores. Moreover, an improved emotional response was observed, characterized by diminished negative affect. GABA supplementation yielded ameliorations in depression scores as per the Depression, Anxiety, and Stress Scale (DASS-21). Notably, an augmented HRV was noted, attributed to heightened parasympathetic autonomic nervous system predominance. GABA supplementation elicited noteworthy enhancements in heart rate variability, emotional response, depression mitigation, and sleep efficiency following a 90-day supplementation.

A Combination of Gamma-Aminobutyric Acid, Glutamic Acid, Calcium, Thiamine, Pyridoxine, and Cyanocobalamin vs Ginger Extract in the Management of Chronic Motion Sickness: A Clinical Evaluation.

Background: Motion sickness (kinetosis) is a common and temporarily incapacitant ailment, manageable with behavioral as well as pharmacological measures. Objective: To assess the effectiveness and safety of a combination of gamma-aminobutyric acid, glutamic acid, calcium, thiamine, pyridoxine, and cyanocobalamin (Group A) (n = 170) and extract of Zingiber officinale (ginger) (Group B) (n = 165) in the management of chronic complaints consistent with motion sickness. Methods: Both groups were tested according to the following end points, under self-paired as well as comparative study designs: reduction of ≥20 score points in the total motion sickness assessment questionnaire (MSAQ) score, percentage of patients presenting a reduction of the total MSAQ score, absolute MSAQ score reduction, physician's assessment scores, final overall assessment of study medication, and willingness to continue treatment. Safety was also evaluated. Results: There was a statistically significant better performance under both study designs for Group A (P = 0.05 using different statistical tests) in all end points. Both regimens were safe, with different neurological and gastrointestinal tolerability outcomes. Conclusions: Group A and Group B regimens were effective and safe in the management of chronic complaints consistent with motion sickness and the Group A regimen was more effective than Group B.

Molecular mechanisms underlying the neuroprotection of environmental enrichment in Parkinson's disease.

Parkinson's disease is the most common movement disorder, affecting about 1% of the population over the age of 60 years. Parkinson's disease is characterized clinically by resting tremor, bradykinesia, rigidity and postural instability, as a result of the progressive loss of nigrostriatal dopaminergic neurons. In addition to this neuronal cell loss, Parkinson's disease is characterized by the accumulation of intracellular protein aggregates, Lewy bodies and Lewy neurites, composed primarily of the protein α-synuclein. Although it was first described almost 200 years ago, there are no disease-modifying drugs to treat patients with Parkinson's disease. In addition to conventional therapies, non-pharmacological treatment strategies are under investigation in patients and animal models of neurodegenerative disorders. Among such strategies, environmental enrichment, comprising physical exercise, cognitive stimulus, and social interactions, has been assessed in preclinical models of Parkinson's disease. Environmental enrichment can cause structural and functional changes in the brain and promote neurogenesis and dendritic growth by modifying gene expression, enhancing the expression of neurotrophic factors and modulating neurotransmission. In this review article, we focus on the current knowledge about the molecular mechanisms underlying environmental enrichment neuroprotection in Parkinson's disease, highlighting its influence on the dopaminergic, cholinergic, glutamatergic and GABAergic systems, as well as the involvement of neurotrophic factors. We describe experimental pre-clinical data showing how environmental enrichment can act as a modulator in a neurochemical and behavioral context in different animal models of Parkinson's disease, highlighting the potential of environmental enrichment as an additional strategy in the management and prevention of this complex disease.

Current Medical Treatment for Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

The controversial role of the vagus nerve in mediating ghrelin's actions: gut feelings and beyond.

Ghrelin is a stomach-derived peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) and displays a plethora of neuroendocrine, metabolic, autonomic and behavioral actions. It has been proposed that some actions of ghrelin are exerted via the vagus nerve, which provides a bidirectional communication between the central nervous system and peripheral systems. The vagus nerve comprises sensory fibers, which originate from neurons of the nodose and jugular ganglia, and motor fibers, which originate from neurons of the medulla. Many anatomical studies have mapped GHSR expression in vagal sensory or motor neurons. Also, numerous functional studies investigated the role of the vagus nerve mediating specific actions of ghrelin. Here, we critically review the topic and discuss the available evidence supporting, or not, a role for the vagus nerve mediating some specific actions of ghrelin. We conclude that studies using rats have provided the most congruent evidence indicating that the vagus nerve mediates some actions of ghrelin on the digestive and cardiovascular systems, whereas studies in mice resulted in conflicting observations. Even considering exclusively studies performed in rats, the putative role of the vagus nerve in mediating the orexigenic and growth hormone (GH) secretagogue properties of ghrelin remains debated. In humans, studies are still insufficient to draw definitive conclusions regarding the role of the vagus nerve mediating most of the actions of ghrelin. Thus, the extent to which the vagus nerve mediates ghrelin actions, particularly in humans, is still uncertain and likely one of the most intriguing unsolved aspects of the field.

Ex vivo and in vitro inhibitory potential of Kava extract on monoamine oxidase B activity in mice.

Background and aim: This study investigated the effect of Kava extract (Piper methysticum), a medicinal plant that has been worldly used by its anxiolytic effects, on monoamine oxidase (MAO) activity of mice brain after 21 days of treatment as well as anxiolytic and locomotor behavior. Furthermore, the in vitro inhibitory profile of Kava extract on MAO-B activity of mouse brain was evaluated. Experimental procedure: Mice were treated with Kava extract (10, 40, 100 and 400 mg/kg) for 21 days by gavage. After behavioral analysis (plus maze test and open field), MAO activity in different mouse brain structures (cortex, hippocampus, region containing the substantia nigra and striatum) were performed. MAO-B inhibitory profile was characterized in vitro. Results: The treatment with Kava extract (40 mg/kg) increased the percentage of entries of mice into the open arms. Ex vivo analysis showed an inhibition on MAO-B activity caused by Kava extract in cortex (10 mg/kg) and in the region containing the substantia nigra (10 and 100 mg/kg). In vitro, Kava extract also reversibly inhibited MAO-B activity with IC50 = 14.62 µg/mL and, increased Km values at the concentrations of 10 and 30 µg/mL and decreased Vmax value at 100 µg/mL. Conclusion: Kava extract showed different effects on MAO-B isoform depending on the brain structure evaluated. Therefore, the use of Kava extract could be promissory in pathologies where MAO-B is the pharmacological target.

Cholecystokinin-Mediated Neuromodulation of Anxiety and Schizophrenia: A "Dimmer-Switch" Hypothesis.

Cholecystokinin (CCK), the most abundant brain neuropeptide, is involved in relevant behavioral functions like memory, cognition, and reward through its interactions with the opioid and dopaminergic systems in the limbic system. CCK excites neurons by binding two receptors, CCK1 and CCK2, expressed at low and high levels in the brain, respectively. Historically, CCK2 receptors have been related to the induction of panic attacks in humans. Disturbances in brain CCK expression also underlie the physiopathology of schizophrenia, which is attributed to the modulation by CCK1 receptors of the dopamine flux in the basal striatum. Despite this evidence, neither CCK2 receptor antagonists ameliorate human anxiety nor CCK agonists have consistently shown neuroleptic effects in clinical trials. A neglected aspect of the function of brain CCK is its neuromodulatory role in mental disorders. Interestingly, CCK is expressed in pivotal inhibitory interneurons that sculpt cortical dynamics and the flux of nerve impulses across corticolimbic areas and the excitatory projections to mesolimbic pathways. At the basal striatum, CCK modulates the excitability of glutamate, the release of inhibitory GABA, and the discharge of dopamine. Here we focus on how CCK may reduce rather than trigger anxiety by regulating its cognitive component. Adequate levels of CCK release in the basal striatum may control the interplay between cognition and reward circuitry, which is critical in schizophrenia. Hence, it is proposed that disturbances in the excitatory/ inhibitory interplay modulated by CCK may contribute to the imbalanced interaction between corticolimbic and mesolimbic neural activity found in anxiety and schizophrenia.

Potential of Germination in Selected Conditions to Improve the Nutritional and Bioactive Properties of Moringa (Moringa oleifera L.).

Moringa oleifera L. is greatly appreciated for its high content of phytochemicals. Although most parts of moringa tree have been widely studied, seeds remained scarcely explored. The first goal of this study was to investigate the effectiveness of germination to improve the nutritional composition (proximate composition and levels of vitamins B1 and B2), content of bioactive compounds (glucosinolates, phenolics and γ-aminobutyric acid, GABA) and antioxidant activity of moringa seed. Germination improved protein, fat, fiber, riboflavin, phenolics, some individual glucosinolates (GLS) and GABA contents, as well as the antioxidant potential in moringa sprouts, but the extent of the improvement depended on germination conditions. The second objective of this work was to identify the optimal germination conditions to maximize nutritional and bioactive quality of moringa by applying multi-response optimization (response surface methodology, RSM). RSM models indicated that 28 °C and 24 h were the optimal conditions to enhance the accumulation of riboflavin, phenolics and antioxidant activity of sprouts, while the highest GABA and total GLS contents were observed at 36 °C for 96 h and thiamine achieved the maximum content at 36 °C for 24 h. These results show that moringa sprouts are promising functional foods that might be also used as ingredients for the elaboration of novel foodstuffs.

Synthesis and insecticidal activity studies of novel phenylpyrazole derivatives containing arylimine or carbimidate moiety.

Phenylpyrazole insecticides are successful for crop protection and public hygiene by blocking gamma-aminobutyric acid (GABA)-gated chloride channels and glutamate-gated chloride (GluCl) channels. A series of novel phenylpyrazoles containing arylimine or 1-methoxyaryl groups were designed and synthesized. The addition reaction of methanol to the imines 1-11 was investigated and the cayno addition products 13-15 were obtained. The compounds 1-15 were confirmed by 1H NMR and elemental analysis. The results of bioassay indicated that some compounds exhibited comparable bioactivity to fipronil against a broad spectrum of insects such as bean aphid (Aphis craccivora), mosquito (Culex pipiens pallens), diamondback moth (Plutella xylostella) and Oriental armyworm (Mythimna separata). Especially, the foliar contact activity against bean aphid of compound 7 at 10 µg mL-1 was 68%, the larvacidal activity against mosquito of compounds 5, 13 and 15 at 0.0025 µg mL-1 was 100%, the larvacidal activity against diamondback moth of compounds 9 and 11 at 0.05 µg mL-1 was 100%, the larvacidal activity against Oriental armyworm of compound 9 at 1 µg mL-1 was 100%. The 3-cayno moiety on pyrazole ring was essential for the high insecticidal activities against bean aphid, diamondback moth and Oriental armyworm, while the 3-carbimidate moiety on pyrazole ring was crucial to the excellent high insecticidal activities against mosquito.

GABAA receptor family: overview on structural characterization.

The pentameric γ-aminobutyric acid type A receptors are ion channels activated by ligands, which intervene in the rapid inhibitory transmission in the mammalian CNS. Due to their rich pharmacology and therapeutic potential, it is essential to understand their structure and function thoroughly. This deep characterization was hampered by the lack of experimental structural information for many years. Thus, computational techniques have been extensively combined with experimental data, in order to undertake the study of γ-aminobutyric acid type A receptors and their interaction with drugs. Here, we review the exciting journey made to assess the structures of these receptors and outline major outcomes. Finally, we discuss the brand new structure of the α1ß2γ2 subtype and the amazing advances it brings to the field.

Effect of di(2-ethylhexyl) phthalate on the neuroendocrine regulation of reproduction in adult male rats and its relationship to anxiogenic behavior: Participation of GABAergic system.

The endocrine disruptor di-(2-ethylhexyl) phthalate (DEHP) is used in a variety of consumer products made with polyvinyl chloride and also in the manufacture of medical devices. DEHP disrupts reproductive tract development in an antiandrogenic manner and also may induce neurobehavioral changes. The aim of this study was to investigate the effects of chronic postnatal exposure to DEHP (30 mg/kg body weight/day, orally from birth to day 60) on the neuroendocrine regulation of the gonadal axis and its impact on the anxiety-like behavior in adult male rats, as well as the probable participation of the GABAergic system in these effects. DEHP produced a significant increase in plasmatic luteinizing hormone and follicle stimulating hormone, as well as significant testosterone decrease, accompanied with a decrease in hypothalamic gamma-aminobutyric acid (GABA) concentration. On the other hand, DEHP increased the anxiety-like behavior in the elevated plus maze test, evidenced by a significant decrease in the percentages of time spent in the open arms and the frequency in the open arm entries and a significant increase in the percentage of time spent in closed arms. Neuroendocrine and behavioral effects were reversed by GABA agonists, muscimol (2 mg/kg i.p. ) and baclofen (10 mg/kg i.p.). In conclusion, chronic DEHP postnatal exposure induced a disruption in the neuroendocrine regulation of the testicular axis in young adult male rats, and this effect was correlated with an anxiety-like behavior. Since GABA agonists reversed these effects, the results suggest that GABA could participate in the modulation of reproductive and behavioral DEHP effects.

Orthosteric and benzodiazepine cavities of the α1ß2γ2 GABAA receptor: insights from experimentally validated in silico methods.

γ-aminobutyric acid-type A (GABAA) receptors mediate fast synaptic inhibition in the central nervous system of mammals. They are modulated via several sites by numerous compounds, which include GABA, benzodiazepines, ethanol, neurosteroids and anaesthetics among others. Due to their potential as targets of novel drugs, a detailed knowledge of their structure-function relationships is needed. Here, we present the model of the α1ß2γ2 subtype GABAA receptor in the APO state and in complex with selected ligands, including agonists, antagonists and allosteric modulators. The model is based on the crystallographic structure of the human ß3 homopentamer GABAA receptor. The complexes were refined using atomistic molecular dynamics simulations. This allowed a broad description of the binding modes and the detection of important interactions in agreement with experimental information. From the best of our knowledge, this is the only model of the α1ß2γ2 GABAA receptor that represents altogether the desensitized state of the channel and comprehensively describes the interactions of ligands of the orthosteric and benzodiazepines binding sites in agreement with the available experimental data. Furthermore, it is able to explain small differences regarding the binding of a variety of chemically divergent ligands. Finally, this new model may pave the way for the design of focused experimental studies that will allow a deeper description of the receptor.

Anesthesia and anesthetic action mechanism of essential oils of Aloysia triphylla and Cymbopogon flexuosus in silver catfish (Rhamdia quelen).

OBJECTIVES: To document the time for anesthesia induction and recovery using different concentrations of essential oils (EOs) of Cymbopogon flexuosus and Aloysia triphylla in silver catfish (Rhamdia quelen), and to determine whether the mechanism of action of either EO involves the benzodiazepine (BDZ) site of the GABAA receptor. STUDY DESIGN: Experimental study. ANIMALS: A total of 144 silver catfish, length 7.5 ± 1.1 cm, weighing 3.95 ± 0.85 g. METHODS: Essential oils were evaluated at concentrations of 25, 150 and 300 µL L-1, and also ethanol alone (seven groups, n = 6 per group). Induction of sedation or anesthesia and recovery were assessed. In a further six groups (n = 6 per group), fish were exposed to both EOs (25, 150 or 300 µL L-1) with diazepam 150 µm, and also diazepam (10 µm) alone. Flumazenil (5 or 10 µm) was added to the recovery water of fish exposed to diazepam (150 µm) or both EOs (150 and 300 µL L-1) (total of 10 groups = 60 fish). RESULTS: Both EOs induced anesthesia at concentrations of 150 and 300 µL L-1, and sedation at 25 µL L-1. There was no significant difference between EOs for reaching deep anesthesia; there was a significantly longer recovery time for the EO of C. flexuosus. The addition of diazepam (150 µm) resulted in faster induction of anesthesia with both EOs, with no significant change in recovery times. Flumazenil (10 µm) reversed the diazepam-induced anesthesia, but not the anesthesia induced by EOs. CONCLUSIONS AND CLINICAL RELEVANCE: The EO of C. flexuosus induced effective sedation (25 µL L-1) and anesthesia (150 and 300 µL L-1) without short-term mortality. The modulation of the BDZ site of the GABAA receptor in the anesthetic action mechanism of both EOs was not demonstrated.

Evidence for increased motor cortical facilitation and decreased inhibition in atypical depression.

OBJECTIVE: Major depressive disorder (MDD) is a clinically heterogeneous condition. However, the role of cortical glutamate and gamma-aminobutyric acid (GABA) receptor-mediated activity, implicated in MDD pathophysiology, has not been explored in different MDD subtypes. Our aim was to assess the atypical and melancholic depression subtypes regarding potential differences in GABA and glutamate receptor-mediated activity through established transcranial magnetic stimulation (TMS) neurophysiological measures from the motor cortex. METHOD: We evaluated 81 subjects free of antidepressant medication, including 21 healthy controls and 20 patients with atypical, 20 with melancholic, and 20 with undifferentiated MDD. Single and paired-pulse TMS paradigms were used to evaluate intracortical facilitation (ICF), cortical silent period (CSP), and short intracortical inhibition (SICI), which index glutamate, GABAB receptor-, and GABAA receptor-mediated activity respectively. RESULTS: Patients with MDD demonstrated significantly decreased mean CSP values than healthy controls (Cohen's d = 0.22-0.3, P < 0.01 for all comparisons). Atypical depression presented a distinct cortical excitability pattern of decreased cortical inhibition and increased cortical facilitation, that is, an increased mean ICF and SICI ratios than other depression subtypes (d = 0.22-0.33, P < 0.01 for all comparisons). CONCLUSION: Different MDD subtypes may demonstrate different neurophysiology in relation to GABAA and glutamatergic activity. TMS as an investigational tool might be useful to distinguish between different MDD subtypes.

Effect of germination on main physiology and biochemistry metabolism of sorghum seeds / Efeito da germinação no principal metabolismo fisiologico e bioquímico de sementes de sorgo

The main physiology and biochemistry metabolism including amino acids composition and gamma-aminobutyric acid (GABA) content of sorghum during 3-day germination period was investigated. Respiratory rate increased during germination. Protease activity, free amino acid and reducing sugar content increased with germination time. While moisture, protein, fat and starch content decreased, significantly. Meanwhile, amino acid composition redistributed and the relative content of essential amino acids increased except for leucine and valine. In addition, some nonessential amino acids content such as proline, glycine and histidine was largely enhanced by germination. GABA content increased about 3 folds after germination. Furthermore, combining tannin (the main antinutritional factor) was converted to be free and solvable. These results greatly suggest that germinated sorghum could be a functional food rich in GABA and other health-promoting nutrients.

O principal metabolismo fisiologico e bioquímico incluindo composição de aminoácidos e teor em ácido gama-aminobutírico (GABA), do sorgo durante o período de germinação 3-dia foram investigados. A frequência respiratória aumentou durante a germinação. A atividade de proteases, aminoácidos livres e redução do teor de açúcar aumentou com o tempo de germinação. Enquanto umidade, proteína, gordura e teor de amido diminuiram, significativamente. Enquanto isso, a composição de aminoácidos redistribuído e o teor relativo de ácidos aminados essenciais aumentaram, exceto para leucina e valina. Além disso, alguns conteúdos não essenciais de aminoácidos, tais como prolina, glicina e histidina foram bem melhorados pela germinação. O conteúdo GABA aumentou cerca de 3 dobras após a germinação. Além disso, a combinação de tanino (o principal factor anti-nutricional) foi convertido para ser livre e solúvel. Estes resultados sugerem fortemente que o sorgo germinado pode ser um alimento funcional rico em GABA e outros nutrientes que promovem a saúde.

Efecto de la alopregnanolona sobre la ansiedad en ratas con separación materna durante la lactancia / The effect of allopregnanolone on anxiety induced in rats separated from their young during breastfeeding

Antecedentes. La relación madre-hijo y el cuidado parental al recién nacido son fundamentales en el desarrollo fisiológico y emocional de los individuos. Evidencias asocian el estrés temprano con el desarrollo de enfermedades mentales. El modelo de separación materna durante la lactancia (SMDL) se ha utilizado para inducir estrés temprano en ratas y estudiar efectos a largo plazo. Diversos estudios han encontrado que, en ratas separadas de sus madres, disminuyen los niveles del receptor GABA-A y esos bajos niveles están asociados a comportamientos ansiosos. Objetivo. Evaluar el efecto de la alopregnanolona, un neuroesteroide agonista del receptor GABA-A, sobre la ansiedad inducida por SMDL. Materiales y métodos. Se utilizaron 30 ratas Wistar dividas en dos grupos, uno control y uno experimental (SMDL). La SMDL se realizó desde el día postnatal 1 hasta el día postnatal 21, durante 180 minutos en la mañana y 180 minutos en la tarde. Desde el día 22 los sujetos se alojaron en cajas por sexo y tratamiento y continuaron su desarrollo normal hasta el día 60, en el que se hizo la inyección con alopregnanolona y la prueba comportamental en el laberinto en cruz elevado. Resultados. El estrés crónico causado por la SMDL afecta el comportamiento de los individuos, perfil comportamental que varía dependiendo del sexo. Se encontró que los machos presentan comportamientos más ansiosos que las hembras, las cuales a su vez muestran más actividad locomotora y exploración Conclusiones. Al aplicar alopregnanolona el repertorio comportamental varía en los animales con SMDL; estos resultados sugieren que la alopregnanolona, a través de su unión al receptor GABA-A, puede llegar a revertir los efectos de la separación materna, sobre los comportamientos relacionados con ansiedad.

Background. The mother-child relationship and parental care for the newborn are fundamental in individuals' physiological and emotional development. Evidence-based research associates early stress with the development of mental illnesses. Maternal separation during lactation (MSDL) models have been used to induce early stress in rats and for studying the long-term effects of such intervention. Several studies have found decreased GABA-A receptor levels in separated rats from their mothers and such low levels have been associated with anxious behaviour. Objective. Assessing the effect of allopregnanolone (a GABA-A receptor neurosteroid agonist) on MSDL-induced anxiety. Materials and methods. Thirty Wistar rats were divided into two groups: control and experimental (MSDL). SMDL occurred for 180 minutes in the morning and 180 minutes in the afternoon. Subjects were housed in boxes by gender and treatment following day 22 and their normal development was allowed to continue until day 60 when they were injected with allopregnanolone and underwent a behavioural test in an elevated plus maze (EPM). Results. Chronic stress induced by MSDL affected individuals' behaviour, their behavioural profile varying according to their gender. Males exhibited more anxious behaviour than females who engaged in more locomotive and exploratory activity. Conclusions. MSDL animals' behavioural repertoire varied due to the allopregnanolone injection, suggesting that the effect of allopregnanolone due to GABA-A receptor interaction could reverse the effects of maternal separation on anxiety-related behaviour.

Interconnectivity of sympathetic and sleep networks is mediated through reduction of gamma aminobutyric acidergic inhibition in the paraventricular nucleus.

Chronic short sleep duration has been linked to sympathoexcitation and increased risk of cardiovascular disease. The central nervous system plays an important role in the regulation of sympathetic activity. Thus, the present study evaluates the pre-autonomic neurones in the paraventricular nucleus of the hypothalamus and rostral ventrolateral medulla after sleep restriction using various protein expression measurements and electrophysiological approaches. Wistar male rats were assigned randomly to two experimental groups: control or sleep restriction for 14 days. Sleep restriction was defined as 20 h of paradoxical sleep deprivation followed by a 4 h sleep permission period using the modified multiple platform method. Micropunches of the paraventricular nucleus of the hypothalamus and rostral ventrolateral medulla were dissected to evaluate the protein expression of angiotensin II receptor, type 1 (AT1), AT2, gamma aminobutyric acidA ) (N-methyl-d-aspartate receptor1) and neuronal nitric oxide synthase neuronal nitric oxide synthase isoform through immunoblotting. Sleep restriction induced a down-regulation of the gamma aminobutyric acidA receptor in the paraventricular nucleus of the hypothalamus. Microinjection of bicuculline, a gamma aminobutyric acid receptor blocker, into the paraventricular nucleus of the hypothalamus increased renal sympathetic activity renal sympathetic nerve activity, mean arterial pressure and heart rate in anaesthetized control rats. However, the amplitude and frequency of renal sympathetic nerve activity was higher in the sleep restriction group. These findings suggest that gamma aminobutyric acidergic inhibition within the paraventricular nucleus of the hypothalamus is involved in sympathoexcitation induced by sleep restriction.

Baclofeno intratecal para el tratamiento de la espasticidad. Reporte de caso con revisión temática / Intrathecal baclofen for the treatment of spasticity. Case report with thematic review

Introducción: La espasticidad es desencadenada por una alteración en el sistema nervioso central; puede presentarse de manera local o generalizada. La severidad de los síntomas —entre ellos, limitación funcional, deformidad, dolor, trastorno del sueño, depresión y múltiples incapacidades— depende de las zonas comprometidas. El tratamiento de la enfermedad se basa en la terapia física y es complementado con correctores de postura, algunas intervenciones quirúrgicas y terapia farmacológica. El baclofeno es un medicamento útil en esta patología. La vía de administración inicial siempre es oral, sin embargo por su baja biodisponibilidad o mala tolerancia en algunos pacientes se requiere la vía intratecal. Objetivo: presentar una revisión de la literatura aprovechando el reporte de un caso de una paciente con diagnóstico de tetraparesia espástica que recibió tratamiento con baclofeno intratecal mediante la implantación de una bomba de terapia intratecal (BTI). Métodos y materiales: Se realizó una búsqueda en las bases de datos EBSCO, MEDLINE y OVID, que incluyó artículos de revisiones sistemáticas, ensayos clínicos, revisiones narrativas y series de casos, entre 1995 y 2012, para la realización de una revisión narrativa no sistemática y reporte de un caso. Resultados: Se tuvieron en cuenta un total de 35 artículos para la realización de la actualización en el tema propuesto. Conclusiones: El uso del baclofeno mediante la implantación de BTI es una alternativa eficaz y segura para el tratamiento de los pacientes con espasticidad severa y refractaria al tratamiento oral convencional.

Introduction: Spasticity is triggered by a central nervous system disorder and may be local or generalized. The severity of symptoms, including functional limitation, deformity, pain, sleep disorders, depression and multiple disabilities, depends on the areas involved. The treatment of the disease is based on physical therapy and complemented with posture correcting devices, a few surgical interventions and drug therapy. Baclofen is a useful drug for this pathology and is usually administered orally; however, due to its low bioavailability or poor tolerance some patients require intrathecal administration. Objective: The purpose of this article is to present a literature review based on a case report of a patient with a diagnosis of spastic tetraparesis, receiving intrathecal baclofen treatment through an implantable intrathecal therapy pump (ITP). Methods and materials: A database search was conducted in EBSCO, MEDLINE and OVID that included systematic review articles, clinical trials, narrative reviews and case series between 1995 and 2012, for a non-systematic narrative review and a case report. Results: 35 articles were considered in total for an update on the topic suggested. Conclusions: Baclofen use through an implanted ITP is an effective and safe option for treating patients with severe spasticity refractory to conventional oral therapy.