Neuroscience
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Schizophrenia (SZ) is a neurodevelopmental-associated disorder strongly related to environmental factors, such as hypoxia. Because there is no cure for SZ or any pharmacological approach that could revert hypoxia-induced cellular damages, we evaluated whether modulators of sirtuins could abrogate hypoxia-induced mitochondrial deregulation as a neuroprotective strategy. Firstly, astrocytes from control (Wistar) and Spontaneously Hypertensive Rats (SHR), a model of both SZ and neonatal hypoxia, were submitted to chemical hypoxia. ⋯ Our data indicate that sirtuins modulation reduces cell death increasing the acetylation of histone 3. This outcome is related to the rescue of loss of mitochondrial membrane potential, changes in mitochondrial calcium buffering capacity, decreased O2-rad levels and increased expression of metabolic regulators (Nrf-1 and Nfe2l2) and mitochondrial content. Such findings are relevant not only for hypoxia-associated conditions, named pre-eclampsia but also for SZ since prenatal hypoxia is a relevant environmental factor related to this burdensome neuropsychiatric disorder.
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Parkinson's disease (PD) is the fastest-growing neurodegenerative disease, with pathogenic causes elusive and short of effective treatment options. Investigations have found that dairy products positively correlate with the onset of PD, but the mechanisms remain unexplored. As casein is an antigenic component in dairy products, this study assessed if casein could exacerbate PD-related symptoms by stimulating intestinal inflammation and unbalanced intestinal flora and be a risk factor for PD. ⋯ Therefore, our results suggested that casein could reactivate dopaminergic nerve injury and intestinal inflammation and exacerbate intestinal flora disorder and its metabolites in convalescent PD mice. These damaging effects might be related to disordered protein digestion and gut microbiota in these mice. These findings will provide new insights into the impact of milk/dairy products on PD progression and supply information on dietary options for PD patients.
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Cerebral ischemic reperfusion injury could emanate a cascade of events ensuing in neural death and severe neurobehavioural deficits. The currently available interventions have failed to target the multimodal, interlinked mechanisms that operate cerebral ischemia-induced damage and functional loss. So an integrative intervention has become a mandate to overcome the deleterious mechanisms involved in cerebral ischemic pathophysiology. ⋯ The BBB integrity was well preserved in the combination group when compared with the lesion and standalone groups. Moreover, the combined intervention reduced the level of pro-inflammatory cytokines TNFα, NFkB, IL1α, IL1-β, IL-6, CD68, COX-2, and mRNA expression of inflammatory genes IL1α, IL1-β, IL-6, IBA-1, and COX-2 effectively. In conclusion, the present study suggests that rMCAo induced neuroinflammation and neurobehavioural alterations were attenuated by intervention with a combination of Fucoidan and cerebrolysin; Further, Fucoidan and Cerebrolysin combination improved the ischemic tolerance level by promoting the proteins and genes that regulate the inflammatory cytokines and in aiding better recovery after ischemic reperfusion injury.
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Experimental autoimmune encephalomyelitis (EAE) is an animal model of Inflammatory central nervous system (CNS) disease. Dark agouti (DA) rats immunized with full-length myelin oligodendrocyte glycoprotein (MOG1-125) typically develop a relapsing-remitting EAE form characterized by predominant demyelinating involvement of the spinal cord and optic nerve. Visually evoked potentials (VEP) are a useful objective tool to assess the optic nerve function and monitor electrophysiological changes in optic neuritis (ON). ⋯ These findings suggest that VEPs may be a reliable biomarker reflecting the optic nerve involvement in EAE. Moreover, the use of a minimally invasive device enables observation of VEP changes over time in MOG-EAE DA rats. Our findings may have important implications for testing the potential neuroprotective and regenerative effects of new therapies for CNS demyelinating diseases.
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Memories already consolidated when reactivated return to a labile state and can be modified, this process is known as reconsolidation. It is known the Wnt signaling pathways can modulate hippocampal synaptic plasticity as well as learning and memory. Yet, Wnt signaling pathways interact with NMDA (N-methyl-D-aspartate) receptors. ⋯ Moreover, the impairment induced by DKK1 was blocked by the administration of the agonist of the NMDA receptors glycine site, D-Serine, immediately and 2 h after reactivation session. We found that hippocampal canonical Wnt/β-catenin is necessary to the reconsolidation of CFC memory at least two hours after reactivation, while non-canonical Wnt/Ca2+ signaling pathway is not involved in this process and, that there is a link between Wnt/β-catenin signaling pathway and NMDA receptors. In view of this, this study provides new evidence regarding the neural mechanisms underlying contextual fear memory reconsolidation and contributes to provide a new possible target for the treatment of fear related disorders.