Effects of long-term social isolation on central, behavioural and metabolic parameters in middle-aged mice.

Social isolation gained discussion momentum due to the COVID-19 pandemic. Whereas many studies address the effects of long-term social isolation in post-weaning and adolescence and for periods ranging from 4 to 12 weeks, little is known about the repercussions of adult long-term social isolation in middle age. Thus, our aim was to investigate how long-term social isolation can influence metabolic, behavioural, and central nervous system-related areas in middle-aged mice. Adult male C57Bl/6 mice (4 months-old) were randomly divided into Social (2 cages, n = 5/cage) and Isolated (10 cages, n = 1/cage) housing groups, totalizing 30 weeks of social isolation, which ended concomitantly with the onset of middle age of mice. At the end of the trial, metabolic parameters, short-term memory, anxiety-like behaviour, and physical activity were assessed. Immunohistochemistry in the hippocampus (ΔFosB, BDNF, and 8OHDG) and hypothalamus (ΔFosB) was also performed. The Isolated group showed impaired memory along with a decrease in hippocampal ΔFosB at dentate gyrus and in BDNF at CA3. Food intake was also affected, but the direction depended on how it was measured in the Social group (individually or in the group) with no alteration in ΔFosB at the hypothalamus. Physical activity parameters increased with chronic isolation, but in the light cycle (inactive phase), with some evidence of anxiety-like behaviour. Future studies should better explore the timepoint at which the alterations found begin. In conclusion, long-term social isolation in adult mice contributes to alterations in feeding, physical activity pattern, and anxiety-like behaviour. Moreover, short-term memory deficit was associated with lower levels of hippocampal ΔFosB and BDNF in middle age.

The bee venom active compound melittin protects against bicuculline-induced seizures and hippocampal astrocyte activation in rats.

Epilepsy is a chronic neuropathology characterized by an abnormal hyperactivity of neurons that generate recurrent, spontaneous, paradoxical and synchronized nerve impulses, leading or not to seizures. This neurological disorder affects around 70 million individuals worldwide. Pharmacoresistance is observed in about 30% of the patients and long-term use of antiepileptics may induce serious side effects. Thus, there is an interest in the study of the therapeutic potential of bioactive substances isolated from natural products in the treatment of epilepsy. Arthropod venoms contain neurotoxins that have high affinity for molecular structures in the neural tissue such as receptors, transporters and ion channels both in glial and neuronal membranes. This study evaluated the potential neuroprotective effect of melittin (MEL), an active compound of bee venom, in the bicuculline-induced seizure model (BIC) in rats. Male Wistar rats (3 months, 250-300 g) were submitted to surgery for the implantation of a unilateral cannula in the lateral ventricle. After the recovery period, rats received a microinjection of saline solution or MEL (0.1 mg per animal). Firstly, rats were evaluated in the open field (20 min) and in the elevated plus maze (5 min) tests after received microinjection of saline or MEL. After, 30 min later animals received BIC (100 mg/ml) or saline, and their behaviors were analyzed for 20 min in the open field according to a seizure scale. At the end, rats were euthanized, brains collected and processed to glial fibrillary acidic protein (GFAP) immunohistochemistry evaluation. No changes were observed in MEL-treated rats in the open field and elevated plus maze. However, 90% of MEL-treated animals were protected against seizures induced by BIC. There was an increase in the latency for the onset of seizures, accompanied by a reduction of GFAP-immunoreactivity cells in the dentate gyrus and CA1. Thus, our study suggests that MEL has an anticonvulsant potential, and further studies are needed to elucidate the mechanisms involved in this action.

Eplingiella fruticosa (Lamiaceae) essential oil complexed with ß-cyclodextrin improves its anti-hyperalgesic effect in a chronic widespread non-inflammatory muscle pain animal model.

Eplingiella fruticosa (Lamiaceae), formally known as Hyptis fruticosa, is an important aromatic medicinal herb used in folk medicine in northeastern Brazil. We aimed to evaluate the anti-hyperalgesic effect of essential oil obtained from E. fruticosa (HypEO) complexed with ßCD (HypEO-ßCD) in a chronic widespread non-inflammatory muscle pain animal model (a mice fibromyalgia-like model, FM). The HypEO was extracted by hydro distillation and its chemical composition was determined by GC-MS/FID. Moreover, Fos protein expression in the spinal cord was assessed by immunofluorescence. (E)-caryophyllene, bicyclogermacrene, 1,8-cineole, α-pinene, ß-pinene and 21 other compounds were identified in the HypEO. The treatment with HypEO-ßCD produced a longer-lasting anti-hyperalgesic effect compared to HypEO, without alterations in motor coordination or myorelaxant effects. Moreover, HypEO and HypEO-ßCD produced a significant anti-hyperalgesic effect over 7 consecutive treatment days. Immunofluorescence assay demonstrated a decrease in Fos protein expression in the spinal cord (p < 0.001). We demonstrated that the anti-hyperalgesic effect produced by HypEO was improved after complexation with ß-CD and this seems to be related to the central pain-inhibitory pathway, suggesting the possible use of E. fruticosa for chronic pain management.

Passiflora cincinnata Extract Delays the Development of Motor Signs and Prevents Dopaminergic Loss in a Mice Model of Parkinson's Disease.

Passiflora cincinnata Masters is a Brazilian native species of passionflower. This genus is known in the American continent folk medicine for its diuretic and analgesic properties. Nevertheless, few studies investigated possible biological effects of P. cincinnata extracts. Further, evidence of antioxidant actions encourages the investigation of possible neuroprotective effects in animal models of neurodegenerative diseases. This study investigates the effect of the P. cincinnata ethanolic extract (PAS) on mice submitted to a progressive model of Parkinson's disease (PD) induced by reserpine. Male (6-month-old) mice received reserpine (0.1 mg/kg, s.c.), every other day, for 40 days, with or without a concomitant treatment with daily injections of PAS (25 mg/kg, i.p.). Catalepsy, open field, oral movements, and plus-maze discriminative avoidance evaluations were performed across treatment, and immunohistochemistry for tyrosine hydroxylase was conducted at the end. The results showed that PAS treatment delayed the onset of motor impairments and prevented the occurrence of increased catalepsy behavior in the premotor phase. However, PAS administration did not modify reserpine-induced cognitive impairments. Moreover, PAS prevented the decrease in tyrosine hydroxylase immunostaining in the substantia nigra pars compacta (SNpc) induced by reserpine. Taken together, our results suggested that PAS exerted a neuroprotective effect in a progressive model of PD.

Effects of regular meditative practice on psychological measures of healthy subjects

Introduction: Meditation is described as a method for improving attention and promoting psychological and emotional stability, presenting favorable results on cognitive functions and stress tolerance as well. Recently, studies have shown differences on psychological measurements between meditators and non-meditators. The aim of this study was to investigate the influence of regular practice of meditation on psychological measures of healthy participants in basal conditions or after experimental stress-induction. Methods: Forty-four healthy participants (20 meditators and 24 non-meditators) were evaluated by inventories of life quality, anxiety, mood, sleep quality, depression, and stress. Furthermore, all participants were submitted to working memory tasks (Hanoy tower and Digit Spam) before and after two stress-induction procedures: Stroop Color-word and Serial Subtraction tests. The research protocol was approved by the institutional ethics committee (204/09 - CEP/UFRN, CAAE 0221.0.051.000-09). Results: Our results showed that meditators presented better inventories scores when compared with non-meditators in parameters such as life quality (score 15.6 versus 14.9, p = 0.04), mood (score 6.0 versus 22.5, p = 0.02), and depression (score 2.5 versus 7.0, p = 0.01). Regarding stress levels, 10 % of meditators (against 37.5% of non-meditators) presented low levels of stress (p = 0.04). Moreover, there was an improvement in performance of meditators (23.3 ± 0.8) in relation to non-meditators (19.0 ± 1.0) on digit span task and in Hanoi tower of meditators (165.2 ± 6.1 ) in relation to non-meditation (224.1 ± 13.1) after stress induction. Conclusion: These findings corroborate other studies showing that meditation can provide an improvement in general quality of life as well as the performance of practitioners in memory tasks.

Influência da prática do yoga sobre os sintomas do climatério / Influence of yoga practice on climacteric symptoms

Introdução: Yoga vem sendo praticado há mais de três mil anos e atualmente seu conjunto de técnicas de controle do corpo e da mente tem sido adotado por milhares de pessoas em todo o mundo. Um número crescente de estudos têm atribuído ao yoga benefícios significativos para a reabilitação da saúde do indivíduo. Na mulher, o processo de envelhecimento é marcado pela suspensão da atividade folicular ovariana (menopausa) durante o período do climatério, este caracterizado por uma série de alterações fisiológicas e neuroendócrinas que podem ser acompanhadas por sintomas desconfortáveis e muitas vezes debilitantes. Objetivo: o objetivo deste estudo é investigar os efeitos psicofisiológicos da prática regular do yoga em mulheres que apresentam sintomas do climatério. Método: Noventa mulheres na faixa etária entre 45 e 65 anos, já em menopausa há pelo menos um ano foram divididas em três grupos: Grupo Controle (não participaram das atividades, n = 19), Grupo ginástica suave (2 vezes por semana, n = 31) e Grupo yoga (2 vezes por semana, n = 40). Todas as participantes foram avaliadas antes e ao final do período da intervenção (12 semanas) através dos inventários de síndrome climatérica (MRS: Menopause Rating Scale), depressão (Inventário de Depressão de Beck), estresse (Inventário de Sintomas de Stress para Adultos de Lipp) e medidas de cortisol salivar. O protocolo de pesquisa foi aprovado pelo comitê de ética (582/11/CEP/HUOL, CAAE 09930.000.294-11). Resultados: Nossos resultados mostraram que as voluntárias que praticaram yoga apresentaram redução do índice referente aos sintomas climatéricos após 12 semanas de prática (8,65 ± 1,05) em relação as voluntárias que praticaram ginástica suave (15,13 ± 1,24) e ao grupo controle que não praticou nenhuma atividade (18,58 ± 2,59), esta redução indica uma melhora nos sintomas. Além disso, os grupos ginástica suave (11,65 ± 0,95) e yoga (9,85 ± 1,17) apresentaram uma melhora significativa com relação aos níveis de depressão quando comparados ao grupo controle (18,95 ± 2,66). Após 12 semanas de pratica, os níveis de estresse também foram reduzidos no grupo yoga (0,55 ± 0,14) com relação ao controle (1,74 ± 0,31) e grupo ginástica suave (1,35 ± 0,19). Conclusões: Nossos resultados mostram que a prática deyogapode ser eficazna redução dos sintomas do climatério, além de diminuir os níveis de estresse dessas mulheres, podendo ser considerado como terapia alternativa para o manejo dos sintomas da menopausa.