Neuroscience
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Adolescence is a period of extensive brain maturation. In particular, the regions of the medial prefrontal cortex (mPFC) undergo intense structural and functional refinement during adolescence. Disturbances in mPFC maturation have been implicated in the emergence of multiple psychopathologies during adolescence. ⋯ Moreover, MS induced anxiety-like behaviors, but not anhedonic-like behavior, in adolescents. These results suggest that ELS may disturb neurodevelopmental apoptosis of neurons and early-postnatal proliferation and/or apoptosis of different populations of glial cells in the PLC. ELS-induced aberrations in the postnatal maturation of the PLC may affect cortical network organization and functioning and determine vulnerability to psychopathologies in adolescents.
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Despite the long history of investigations of adrenergic compounds and their biological effects, specific mechanisms of their action in distinct compartments of the motor unit remain obscure. Recent results have suggested that not only skeletal muscles but also the neuromuscular junctions represent important targets for the action of catecholamines. In this paper, we describe the effects of adrenaline and noradrenaline on the frequency of miniature endplate potentials, the quantal content of the evoked endplate potentials and the kinetics of acetylcholine quantal release in the motor nerve endings of the mouse diaphragm. ⋯ Quantal release became more asynchronous under noradrenaline, as evidenced by a greater dispersion of real synaptic delays; in contrast, adrenaline synchronized the release process. Our data suggest an involvement of α and β adrenoreceptors in the diverse modulation of the frequency of miniature endplate potentials, the quantal content of the evoked endplate potentials and the kinetics of acetylcholine quantal secretion in the mouse neuromuscular junction. Moreover, the adrenoblockers affected both the evoked and spontaneous quantal release of acetylcholine, suggesting the presence of endogenous catecholamines in the vicinity of cholinergic synapses.
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Stress, a major precipitant of depression, and antidepressants have major impact on synaptic integrity and plasticity in brain areas, such as hippocampus (HPC) and prefrontal cortex (PFC). We have recently shown that, unlike Wistar rats, rats of the Wistar-Kyoto (WKY) strain fail to respond to chronic antidepressant treatment after exposure to chronic mild stress (CMS) procedure. However, deep brain stimulation (DBS) of PFC was effective in both strains. ⋯ Some other changes in gene expression were identified in dorsal HPC and PFC, particularly in Wistars, that were not normalized by DBS. No effects were identified that were common to both Wistars and WKY. The difference between Wistars and WKY in the balance of overall gene expression in HPC may be relevant to the resistance of WKY rats to antidepressant drug treatment.
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Alpha-Synuclein (α-Syn) is expressed in the central nervous system and the nervous system of the gut (enteric nervous system, ENS), and is well known to be the major constituent of Lewy bodies which are the hallmark of Parkinson's disease. Gastrointestinal disorders frequently manifest several years before motor deficits develop in Parkinson's patients. ⋯ We found that α-Syn is predominantly expressed in cholinergic varicosities, which contain vesicular acetylcholine transporter. α-Syn KO mice had higher enteric neuron density and a larger proportion of cholinergic neurons, notably those containing calretinin, demonstrating a role for α-Syn in regulating development of these neurons. Moreover, α-Syn deletion enhanced the amplitude of synaptically activated [Ca2+]i transients that are primarily mediated by acetylcholine activating nicotinic receptors suggesting that α-Syn modulates the availability of acetylcholine in enteric nerve terminals.
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Alzheimer's disease (AD) is a neurodegenerative disorder classically characterized by cognitive functions impairment. However, its symptomatology is complex and the depression is one of the most frequent behavioral changes in AD. AD pathology includes neuroinflammation and oxidative stress resulting in the Aβ protein accumulation. ⋯ Furthermore, NLC C reduced the Aβ-generated oxidative stress in the prefrontal cortex, evidenced by the increase in the reactive species levels, superoxide dismutase and catalase activities. Importantly, NLC C were more effective than the free curcumin. Thus, we demonstrated the antidepressant-like and antioxidant effects of NLC C in a mouse model of AD, suggesting its therapeutic potential for this disorder.