Neuroscience
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Epidemiological studies have demonstrated that women are less susceptible to Parkinson's disease (PD) than men. Estrogen exposure is hypothesized to confer protection against dopaminergic neuronal loss in patients with PD. Although the accumulation and propagation of α-synuclein (α-Syn) are closely linked to the clinical progression of PD, no relevant research has examined whether α-Syn proteostasis in the brain is altered in women after menopause. ⋯ We observed that the OVX mice exhibited a significant increase in the expression and aggregation of α-Syn in the striatum and midbrain accompanied by impaired motor performance at 3 months after ovariectomy. The accumulation of α-Syn did not result in a significant loss of nigral dopaminergic neurons but did enhance autophagy and neuroglial activation. These findings imply that menopause may disrupt α-Syn proteostasis and exacerbate the accumulation of α-Syn in the basal ganglia circuit.
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Ginkgo biloba L. leaf extract (GBE) has been added in many commercial herbal formulations such as EGb 761 and Shuxuening Injection to treat cardiovascular diseases and stroke worldwide. However, the comprehensive effects of GBE on cerebral ischemia remained unclear. Using a novel GBE (nGBE), which consists of all the compounds of traditional (t)GBE and one new compound, pinitol, we investigated its effect on inflammation, white matter integrity, and long-term neurological function in an experimental stroke model. ⋯ In vitro analyses showed that nGBE treatment reduced the production of IL-1β and TNFα in primary microglia. Administration of nGBE also decreased the SMI-32/MBP ratio and enhanced myelin integrity, thus exhibiting improved white matter integrity at 28 days post stroke. These findings demonstrate that nGBE protects against cerebral ischemia by inhibiting microglia-related inflammation and promoting white matter repair, suggesting that nGBE is a promising therapeutic strategy for long-term recovery after stroke.
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Gastrointestinal (GI) disorders are widely recorded in autism spectrum disorder (ASD), and ASD with GI symptoms is a vital subtype of this disease. Growing evidence suggests altered gut microbiota biomarkers in ASD, but little is known about the gut microbiota of individuals with ASD with GI Symptoms, particularly in early childhood. In our study, the gut microbiota of 36 individuals with ASD along with GI symptoms and 40 typically developing (TD) children were compared using 16S rRNA gene sequencing. ⋯ Furthermore, we constructed a Support Vector Machine classification model, which robustly discriminated individuals with ASD and GI symptoms from TD individuals in a validation set (AUC = 0.88). Our findings provide a deep insight into the roles of the disturbed gut ecosystem in individuals with ASD and GI symptoms aged 3-6 years. Our classification model supports gut microbiota as a potential biomarker for the early identification of ASD and interventions targeting particular gut-beneficial microbiota.
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Neurogenesis occurs throughout adulthood within the dentate gyrus, and evidence indicates that these new neurons play a critical role in both spatial and social memory. However, a vast majority of past research on adult neurogenesis has involved experiments with captive mice and rats, making the generalizability of results to natural settings questionable. We assessed the connection between adult neurogenesis and memory by measuring the home range size of wild-caught, free-ranging meadow voles (Microtus pennsylvanicus). ⋯ Voles with larger ranges also had significantly higher pyknotic cell densities in the entire GCL + SGZ and in the dorsal GCL + SGZ. These results support the hypothesis that cell proliferation and cell death within the hippocampus are involved with spatial memory formation. However, a marker of neurogenesis (DCX+) was not correlated with range size, suggesting that there may be selective cellular turnover in the dentate gyrus when a vole is ranging through its environment.
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Randomized Controlled Trial
Head down tilt 15° in acute ischemic stroke with poor collaterals: a randomized preclinical trial.
Cerebral collaterals are recruited after arterial occlusion with a protective effect on tissue outcome in acute ischemic stroke. Head down tilt 15° (HDT15) is a simple, low cost and accessible procedure that could be applied as an emergency treatment, before recanalization therapies, with the aim to increase cerebral collateral flow. Spontaneously hypertensive rats have been shown to display anatomical differences in morphology and function of cerebral collaterals, compared to other rat strains, resulting in an overall poor collateral circulation. ⋯ HDT15 application increased cerebral perfusion (+16.6% versus +6.1%; p = 0.0040) and resulted in a small reduction of infarct size (83.6 versus 107.1 mm3; - 21.89%; p = 0.0272), but it was not associated with early neurological improvement, compared to flat position. Our study suggests that the response to HDT15 during MCA occlusion is dependent on baseline collaterals. Nonetheless, HDT15 promoted a mild improvement of cerebral hemodynamics even in subjects with poor collaterals, without safety concerns.