Neuroscience
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Accumulation of amyloid peptides in the brain plays a key role in the pathogenesis of Alzheimer's disease (AD). Aggregated beta-amyloid (Aβ) peptide increases intracellular reactive oxygen species associated to a deficient antioxidant defense system. Prefrontal cortex plays a key role in memory and learning and is especially susceptible to oxidative stress. ⋯ Interestingly, we found that an i.c.v. injection of Aβ(1-42) increased lipid peroxidation, reduced total antioxidant capacity level, phase-shifted the daily peak of reduced glutathione, and had a differential effect on the oscillating catalase and glutathione peroxidase specific activity. Thus, elevated levels of Aβ aggregates-a pathogenic hallmark of AD, caused altered temporal patterns of the cellular redox state in prefrontal cortex rat. These findings might contribute, at least in part, to the understanding of the molecular and biochemical basis of redox changes caused by circadian rhythms alterations observed in AD patients.
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Brain-derived neurotrophic factor (BDNF) plays an important role in processes associated with neuroplasticity and neuroprotection. Evidence suggests that decreased BDNF levels in the central nervous system (CNS) represent a mechanism underlying the development of mood disorders. We hypothesize that both congenital and traumatic brain injury (mTBI)-induced blood-brain barrier (BBB) breakdown are responsible for brain BDNF depletion that contributes to the development of depressive-like symptoms. ⋯ No alterations in BDNF levels were observed in mTBI and CMS-exposed HA mice. Moreover, CMS did not induce BBB damage or affect depressive-like behaviours in HA mice despite downregulating Bdnf gene expression. To conclude, BDNF efflux through the mTBI-disrupted BBB is strongly linked to the development of depressive-like behaviours, while the depressive phenotype in mice with congenital BBB dysfunction is independent of BDNF leakage.
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Pain is a major health problem, affecting over fifty million adults in the US alone, with significant economic cost in medical care and lost productivity. Despite evidence implicating nicotinic acetylcholine receptors (nAChRs) in pathological pain, their specific contribution to pain processing in the spinal cord remains unclear given their presence in both neuronal and non-neuronal cell types. Here we investigated if loss of neuronal-specific TMEM35a (NACHO), a novel chaperone for functional expression of the homomeric α7 and assembly of the heteromeric α3, α4, and α6-containing nAChRs, modulates pain in mice. ⋯ These DEGs were mapped onto functional gene networks using the knowledge-based database, Ingenuity Pathway Analysis, and suggests increased neuroinflammation as a potential contributing factor for the hyperalgesia in tmem35a KO mice. Collectively, these findings implicate a heightened inflammatory response in the absence of neuronal NACHO activity. Additional studies are needed to determine the precise mechanism by which NACHO in the spinal cord modulates pain.
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Diffusion-weighted magnetic resonance imaging (DWI) is undergoing constant evolution with the ambitious goal of developing in-vivo histology of the brain. A recent methodological advancement is Neurite Orientation Dispersion and Density Imaging (NODDI), a histologically validated multi-compartment model to yield microstructural features of brain tissue such as geometric complexity and neurite packing density, which are especially useful in imaging the white matter. Since NODDI is increasingly popular in clinical research and fields such as developmental neuroscience and neuroplasticity, it is of vast importance to characterize its reproducibility (or reliability). ⋯ Collectively, the voxel-based approach with Gaussian smoothing kernels of ≥4 mm FWHM and ROI-averaging yielded the highest reproducibility across NDI and ODI maps (CVWS mostly ≤3%, ICC mostly ≥0.8), respectively, whilst smaller kernels and TBSS performed consistently worse. Furthermore, we demonstrate that image quality (signal-to-noise ratio [SNR]) is an important determinant of NODDI metric reproducibility. We discuss the implications of these results for longitudinal and cross-sectional research designs commonly employed in the neuroimaging field.
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Exercise is a promising, cost-effective intervention to augment successful aging and neurorehabilitation. Decline of gray and white matter accompanies physiological aging and contributes to motor deficits in older adults. ⋯ This knowledge will allow us to develop more effective, personalized exercise protocols that meet individual needs, thereby increasing the utility of exercise strategies in clinical and non-clinical settings. Here, we review findings from studies that investigated neurophysiological and molecular changes associated with acute or long-term exercise in healthy, young adults and in healthy, postmenopausal women.