Neuroscience
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Substantial epidemiological evidence shows an increased risk for developing Alzheimer's disease (AD) in people with diabetes. Yet the underlying molecular mechanisms still remain to be elucidated. This article reviews the current studies on common pathological processes of Alzheimer's disease and diabetes with particular focus on potential mechanisms through which diabetes affects the initiation and progression of Alzheimer's disease. Impairment of insulin signaling, inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, APOEε4 and cholesterol appear to be important mediators and are likely to act synergistically in promoting AD pathology.
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In both perceptual and motor learning, numerous studies have shown specificity of learning to the trained eye or hand and to the physical features of the task. However, generalization of learning is possible in both perceptual and motor domains. Here, I review evidence for perceptual and motor learning generalization, suggesting that generalization patterns are affected by the way in which the original memory is encoded and consolidated. ⋯ Such generalization may be supported by sleep, involving functional interactions between low and higher-order brain areas. Repeated exposure to the task may alter generalization patterns of learning and overall offline learning. Development of unifying frameworks across learning modalities and better understanding of the conditions under which learning can generalize may enable to gain insight regarding the neural mechanisms underlying procedural learning and have useful clinical implications.
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It is widely known that prenatal stress (PS) exposure causes depression-like behaviour to offspring, as well as maladaptive responses including neurobiological and physiological changes. However, the underlying mechanism of PS induced juvenile-onset depression remains largely unravelled. The inadequacies of monoamine deficiency hypothesis, the emerging evidence of altered glutamate neurotransmission in mood disorders, as well as our previous studies inspired us to assess the potential role of glutamatergic system in the pathogenesis of juvenile depression. ⋯ We also detected that PS significantly altered the expression of glutamate receptor and glutamate transporters of these depressed rats. In brief, the changes of phosphorylated GluR1 subunit of AMPAR protein level in the hippocampus and frontal cortex, as well as markedly decreased EAAT2 mRNA expression in the hippocampus, striatum and frontal cortex and EAAT3 mRNA expression in the hippocampus of stressed rats were both observed. These results underpinned that glutamate receptors and glutamate transporters might be involved in the progress of depression-like behaviour in juvenile rat offspring induced by PS.
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Persistent exposure to environmental stressors causes dysregulation of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis and alters GABAA receptor (GABAAR) levels throughout the brain. Social subordination in socially housed female rhesus results in distinctive stress-related physiological and behavioral phenotypes that are dependent on the ovarian hormone estradiol (E2). In the present study, we utilized ovariectomized adult female rhesus monkeys undergoing hormone replacement with E2 to test the hypothesis that the chronic psychosocial stress of subordination alters GABAAR binding potential (GABAAR BPND) in limbic regions implicated in emotional processing including the prefrontal cortex, temporal lobe (amygdala and hippocampus), and hypothalamus. ⋯ T1-weighted structural magnetic resonance imaging scans were also acquired for PET scan co-registration, in order to perform a region of interest analysis using the pons as a reference region. Compared to socially dominant females, subordinate females exhibited increased GABAAR BPND in the prefrontal cortex but not in the temporal lobe or the hypothalamus. Administration of astressin B eliminated the status difference in GABAAR BPND in the prefrontal cortex, suggesting that the chronic stressor of social subordination modulates GABAergic tone via effects on CRH and the LHPA axis, at least in prefrontal regions.
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Postural support alters anticipatory postural adjustments (APAs). Efficient adaptation to changes in postural support in reactive and centrally initiated postural synergies is impaired in Parkinson's disease (PD). This study examined whether APAs are affected differently by familiar and novel supports in people with PD, ON and OFF levodopa. ⋯ Controls and PD patients in the OFF state further refined the postural strategy with practice as evidenced by changes in amplitude of vertical ground reaction forces and forces applied to support apparatus within conditions between the initial and final trials. In the ON state, people with PD failed to refine the use of postural supports in any condition. The results suggest that immediate postural adaptation is intact in people with PD and unaffected by levodopa administration but the ability to refine postural adaptations with task experience is compromised by dopamine therapy.