Neuroscience
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Non-rapid eye movement (NREM) sleep electroencephalographic (EEG) delta power (~0.5-4 Hz), also known as slow wave activity (SWA), is typically enhanced after acute sleep deprivation (SD) but not after chronic sleep restriction (CSR). Recently, sleep-active cortical neurons expressing neuronal nitric oxide synthase (nNOS) were identified and associated with enhanced SWA after short acute bouts of SD (i.e., 6h). However, the relationship between cortical nNOS neuronal activity and SWA during CSR is unknown. ⋯ SWA and NREM sleep delta energy (the product of NREM sleep duration and SWA) were positively correlated with enhanced cortical nNOS neuronal activity after 18-h SD but not 5days of SR. That neurons expressing nNOS were active after longer amounts of acute SD (18h vs. 6h reported in the literature) and were correlated with SWA further suggest that these cells might regulate SWA. However, since these neurons were active after CSR when SWA was not enhanced, these findings suggest that mechanisms downstream of their activation are altered during CSR.
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Increasing evidence has linked membrane cholesterol to amyloid precursor protein (APP) processing. β-Sitosterol (BS) is one of the most common forms of plant sterols, with the structure very similar to that of cholesterol. Using HT22 mouse hippocampal cells, this study investigated whether the substitution of membrane cholesterol with BS influences APP metabolism. ⋯ Additional experiments suggest that the effect of membrane BS on APP metabolism is associated with the migration of APP from lipid rafts toward non-raft regions. Given that dietary BS can enter the brain and accumulates in the plasma membrane of brain cells, these results suggest a potential use of BS in the prevention of Alzheimer's disease.
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Major depressive disorder (MDD) is a prevalent debilitating psychiatric mood that contributes to increased rates of disability and suicide. However, the pathophysiology underlying MDD remains poorly understood. A growing number of studies have associated dysfunction of the prefrontal cortex (PFC) with depression, but no proteomic study has been conducted to assess PFC protein expression in a preclinical model of depression. ⋯ Two of the four differential proteins selected for Western blotting validation - glyoxalase 1 and dihydropyrimidinase-related protein 2 - were found to be significantly downregulated in CUMS relative to control rats. In conclusion, proteomic analysis reveals that energy and glutathione metabolism are the most significantly altered biological pathways in the CUMS rat model of depression. Further investigation on these processes and proteins in the PFC is key to a better understanding of the underlying pathophysiology of MDD.
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Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment of a spectrum of anxiety disorders, yet paradoxically they may increase symptoms of anxiety when treatment is first initiated. Despite extensive research over the past 30 years focused on SSRI treatment, the precise mechanisms by which SSRIs exert these opposing acute and chronic effects on anxiety remain unknown. By testing the behavioral effects of SSRI treatment on Pavlovian fear conditioning, a well characterized model of emotional learning, we have the opportunity to identify how SSRIs affect the functioning of specific brain regions, including the amygdala, bed nucleus of the stria terminalis (BNST) and hippocampus. ⋯ With these findings, we propose a model by which acute SSRI administration, by altering neural activity in the extended amygdala and hippocampus, enhances both acquisition and expression of cued fear conditioning, but impairs the expression of contextual fear conditioning. Finally, we review the literature examining the effects of chronic SSRI treatment on fear conditioning in rodents and describe how downregulation of N-methyl-d-aspartate (NMDA) receptors in the amygdala and hippocampus may mediate the impairments in fear learning and memory that are reported. While long-term SSRI treatment effectively reduces symptoms of anxiety, their disruptive effects on fear learning should be kept in mind when combining chronic SSRI treatment and learning-based therapies, such as cognitive behavioral therapy.
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Goal-directed reaching is important for the activities of daily living. Populations of neurons in the primary motor cortex that project to spinal motor circuits are known to represent the kinematics of reaching movements. We investigated whether repetitive practice of goal-directed reaching movements induces use-dependent plasticity of those kinematic characteristics, in a manner similar to finger movements, as had been shown previously. ⋯ Direction and the position of the point of peak velocity of TMS-evoked movements were significantly altered following training and at a 5-min interval following training, while amplitude did not show significant changes. This was accompanied by changes in the motor-evoked potentials (MEPs) of the shoulder and elbow agonist muscles that partly explained the change in direction, mainly by increase in agonist MEP, without significant changes in antagonists. These findings demonstrate that the arm representation accessible by motor cortical stimulation under goes rapid plasticity induced by goal-directed robotic reach training in healthy subjects.