Brain research
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Sexual neurosteroids (SN), namely 17β-estradiol (E2) and 5α-dehydrotestosterone (DHT), are synthesized in the hippocampus, where they induce circuit modifications by changing the number of excitatory spine synapses in a paracrine and sex-specific manner. The mechanisms of this sex-specific synapse turnover, which are likely to affect cognitive functions, are poorly understood. We found that hippocampal neurons synthesize estradiol, which maintains LTP and synapses in females but not in males. ⋯ The essential role of local estrogen on the stability and maintenance of connectivity in the hippocampus is consistent with age-related cognitive decline in women after menopause. In male animals the regulation of synaptic stability and plasticity by locally synthesized sexual steroids remains to be clarified. This article is part of a Special Issue entitled SI: Brain and Memory.
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Studies of human brain malformations, such as lissencephaly and double cortex, have revealed the importance of neuronal migration during cortical development. Afadin, a membrane scaffolding protein, regulates the formation of adherens junctions (AJs) and cell migration to form and maintain tissue structures. Here, we report that mice with dorsal telencephalon-specific ablation of afadin gene exhibited defects similar to human double cortex, in which the heterotopic cortex was located underneath the normotopic cortex. ⋯ These results indicate that afadin is required for the maintenance of AJs of radial glial cells and that the disruption of AJs might cause an abnormal radial scaffold for neuronal migration. In contrast, the proliferation or differentiation of radial glial cells was not significantly affected. Taken together, these findings indicate that afadin is required for the maintenance of the radial glial scaffold for neuronal migration and that the genetic ablation of afadin leads to the formation of double cortex.
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To longitudinally evaluate long- and short-range functional connectivity density (FCD) alteration in cirrhotic patients one month after liver transplantation (LT) and their correlation with cognitive changes by using resting-state functional magnetic resonance imaging (rs-fMRI). ⋯ LT results in favorable effect on cognitive function in cirrhotic patient, which can be reflected by FCD alteration. However, persistence of PCC/PCu functional connectivity disturbance one month after LT indicates complete cognitive function restoration may need a longer time.
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A large percentage of patients subjected to general anesthesia at 65 years and older exhibit postoperative delirium (POD). Here, we test the hypothesis that inhaled anesthetics (IAs), such as Sevoflurane and Isoflurane, act directly on brain vascular endothelial cells (BVECs) to increase blood-brain barrier (BBB) permeability, thereby contributing to POD. Rats of young (3-5 months), middle (10-12 months) and old (17-19 months) ages were anesthetized with Sevoflurane or Isoflurane for 3h. ⋯ Disruption of brain homeostasis due to plasma influx into the brain parenchyma and binding of plasma components (e.g., immunoglobulins) to neurons may contribute to POD. We propose that, in the elderly, exposure to some IAs can cause BBB compromise that disrupts brain homeostasis, perturbs neuronal function and thereby contributes to POD. If unresolved, this may progress to postoperative cognitive decline and later dementia.
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Neuronal apoptosis occurs as a sequel of oxidative stress associated with various neuropathies. In this study, we have investigated the protective effect of farnesol, a sequisterpene on lipopolysaccharide (LPS) induced neurodegeneration through modulation of intrinsic apoptotic cascade in the cortex and hippocampus of Swiss albino mice. Intraperitoneal (i.p.) injection of LPS (250 μg/kg b.wt. for 7 days) resulted in elevated levels of lipid peroxidation, protein carbonyls and 8-Hydroxydeoxyguanosine (8OHdG), with subsequent depletion in the antioxidant status and severe histological aberrations. ⋯ Farnesol treatment also reduced the expulsion of cytochrome c from mitochondria and downregulated caspase 3 activation as revealed by immunoblot analysis. Furthermore, farnesol treatment reduced the expression of Bax and antagonized LPS-induced decrease in anti-apoptotic Bcl-2. Results of this study show that farnesol exerts neuroprotective effect by regulating intrinsic apoptotic cascade through its antioxidant effect during LPS-induced neurodegeneration.