Neuroscience
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Alzheimer's disease (AD) is characterized by progressive and irreversible cognitive and memory impairment. The discovery of familial forms of AD (fAD) in association with specific gene mutations facilitated the generation of numerous rodent models. These models in turn proved valuable for the study of molecular mechanisms underlying AD pathogenesis, and facilitated translational research and preclinical drug development. This study aimed to introduce a new rat model of AD simulating some aspects of the sporadic cases of disease. ⋯ Results from this work suggest that LV-mediated delivery of APPSw/Ind in adult rats represents a cost and time-effective animal model for the study of mechanisms underlying APP-linked fAD pathogenesis. The relevance of this animal model to the study of sporadic AD is discussed.
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The disruptive effects of cocaine on physiological, behavioral and genetic processes are well established. However, few studies have focused on the actions of cocaine on the adult circadian timekeeping system, and none have explored the circadian implications of long-term (weeks to months) cocaine exposure. The present study was undertaken to explore the actions of such long-term cocaine administration on core circadian parameters in mice, including rhythm period, length of the nocturnal activity period and photic entrainment. ⋯ This pattern persisted after cocaine withdrawal. Next, mice exposed to scheduled daily cocaine presentations exhibited free-running periods under constant darkness that were significantly longer than water controls and which also persisted after cocaine withdrawal. These cocaine-induced perturbations of clock timing could produce chronic psychological and physiological stress, contributing to increased cocaine use and dependence.
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Hyperglycemia accentuates the injury produced by anoxia both in the central and peripheral nervous system. To understand whether this is a consequence of changes in metabolic pathways produced by anoxia, the effect of the metabolic substrate used by the rat peripheral nerve on the nerve action potential (NAP) was studied in the presence and absence of anoxia. In the continuously oxygenated state, the NAP was well preserved with glucose, lactate, as well as with high concentrations of sorbitol and fructose but not β-hydroxybutyrate, acetate or galactose. ⋯ These are distinct phenomena. For example, the NAP persisted longest during anoxia in the setting of hyperglycemia but this was the state in which the anoxic damage was most severe. Correlating the results with existing literature on the metabolic functions of Schwann cells and axons generates testable hypotheses for the mechanism of hyperglycemic damage during anoxia and lead to discussions of the role for a metabolic shuttle between Schwann cells and axons as well as a potential important role of glycogen.
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The hippocampus has been established as a site of plasticity during the acquisition of spatial memory. The memory for spatial locations is impaired in patients who develop hepatic encephalopathy (HE). We wondered how the hippocampus can manage different hippocampal-dependent tasks in a type B model of the early evolutive phases of HE induced by triple portal vein ligation. ⋯ Our behavioral results showed impairments in the acquisition of both tasks by the portal hypertension group compared with the sham-operated group. To label brain areas related to these tasks, we marked the expression of the c-Fos protein and revealed high c-Fos immunoreactivity in cornu ammonis 1 (CA1), cornu ammonis 3 (CA3) and entorhinal (Ent) cortex of the PH group compared with the SHAM group in the object-place recognition task and a decrease in c-Fos-positive cells in the reversal task in the CA1, CA3, dentate gyrus (DG), cingulate (CG), prelimbic (PL), and infralimbic (IL) cortices in the PH group compared with the SHAM group. In conclusion, the study corroborated the pivotal role of the hippocampus in spatial memory deficits found in the early stages of type B HE and noted its differential contribution in each of the tasks.