Neuroscience
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Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative disorders that significantly impact well-being. Hyperoside (HYP), a flavonoid found in various plant species, particularly within the genus Hypericin, exhibits diverse pharmacological properties. However, the precise mechanisms underlying the anti-AD and anti-PD effects of HYP remain unclear. ⋯ We systematically assessed the neuroprotective potential of HYP in in vivo and in vitro models of AD and PD. Our findings indicated that HYP can mitigate, intervene in, and treat AD and PD animal models and associated cells through various mechanisms, including anti-oxidative, anti-inflammatory, anti-apoptotic, anti-Aβ aggregation, and cholinesterase inhibitory activities. Therefore, HYP potentially exerts anti-AD and anti-PD effects through diverse mechanisms, making it a promising candidate for therapeutic intervention in both AD and PD.
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Targeted intracranial delivery of molecularly-specific therapies within intricate brain structures poses a formidable challenge due to the heterogeneity of neuronal phenotypes and functions. Here we report the use of an implantable, miniaturized neural drug delivery system permitting dynamic adjustment of pharmacotherapies. ⋯ Remarkably, we demonstrate that micro infusions of U-50488 into the dorsal NASh induces reward-like conditioned place preferences, whereas a mere 1 mm shift ventrally results in conditioned place aversions. The striking precision afforded by this method may prove useful in other neurotherapeutic interventions.
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Multicenter Study
Plasma fibroblast growth factor 21 and risk of cognitive impairment among patients with ischemic stroke.
Previous study reported that plasma fibroblast growth factor 21 (FGF-21) was associated with poor prognosis in patients with ischemic stroke. The purpose of present study was to prospectively investigate the relationship between plasma FGF-21 and post-stroke cognitive impairment (PSCI). ⋯ Elevated plasma FGF-21 level was associated with PSCI at 3 months after stroke independently of established conventional risk factors, suggesting that plasma FGF-21 may have potential prognostic value in risk stratification of PSCI.
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The intercellular communication within the central nervous system (CNS) is of great importance for in maintaining brain function, homeostasis, and CNS regulation. When the equilibrium of CNS is disrupted or injured, microglia are immediately activated and respond to CNS injury. Microglia-derived exosomes are capable of participating in intercellular communication within the CNS by transporting various bioactive substances, including nucleic acids, proteins, lipids, amino acids, and metabolites. ⋯ Meanwhile, we summarized the molecular mechanisms by which the relevant exosomes exert regulatory effects. Exosomes, derived from microglia stimulated by different environments, regulate other nerve cells during the repair of CNS injury, having beneficial or detrimental effects on CNS repair. A comprehensive understanding of the molecular mechanisms underlying their role can provide a robust foundation for the clinical treatment of CNS injury.
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Stress is an independent risk factor for cognitive impairment, with elevated plasma homocysteine (HCY) levels playing a crucial role in stress-induced cognitive decline. While the rise in plasma HCY levels is linked to abnormal peripheral catabolism, the impact of stress on HCY catabolism in the brain remains unclear. This study investigated the effect of stress on HCY metabolism in the brain by analyzing HCY and its metabolic enzymes in the hippocampus and prefrontal cortex. ⋯ Immunofluorescence double-labeling revealed the downregulation of HCY metabolic enzymes in neurons of stressed mice. The transcription factor KLF4 (Kruppel-likefactor4), known for its inhibitory role, increased after stress or glucocorticoid treatment and suppressed the expression of MS, CBS, and CSE, contributing to elevated HCY levels in the brain. These findings offer new insights into the impairment of HCY catabolism in the stressed brain, suggesting that the downregulation of HCY metabolic enzymes may underlie HCY accumulation and exacerbate stress-induced cognitive dysfunction.