Neuroscience
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Although morphine was previously reported to produce an instant induction of c-fos in the striatum, our recent studies have demonstrated that the expression of numerous immediate early genes (IEGs) is significantly elevated at delayed time-points (several hours) after morphine administration. To better dissect the time-course of opioid-produced IEG induction, we used in situ hybridization to examine the expression of the IEGs c-fos, zif268 and arc in the mouse forebrain at several time-points after acute morphine injection. To link drug-produced behavioral changes with the activity of specific neuronal complexes, this study was performed comparatively in the C57BL/6 and DBA/2 mouse strains, which differ markedly in their locomotor responses to opioids and opioid reward. ⋯ The second IEG induction (of arc and of zif268) was more widespread, involving most of the dStr and the cortex. The second IEG induction peaked earlier in the DBA/2 mice than in the C57BL/6 mice (4 h compared with 6 h) and displayed no apparent relation to locomotor behavior. This delayed episode of IEG activation, which has largely been overlooked thus far, may contribute to the development of long-term effects of opioids such as tolerance, dependence and/or addiction.
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Relaxin is an essential pregnancy-related hormone with broad peripheral effects mediated by activation of relaxin-like family peptide 1 receptors (RXFP1). More recent studies suggest an additional role for relaxin as a neuropeptide, with RXFP1 receptors expressed in numerous brain regions. Neurons in an area of the brainstem known as the nucleus incertus (NI) produce relaxin 3 (RLN3), the most recently identified neuropeptide in the relaxin family. ⋯ Cognitive and emotional processes regulated by activity within the HI and AMYG are modulated by both sex and age. The vast majority of studies exploring the influence of sex on age-related changes in the HI and AMYG have focused on sex hormones, with few studies examining the role of neuropeptides. The current findings suggest that changes in relaxin family peptides may contribute to the significant sex differences observed in these brain regions as a function of aging.
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The blood retinal barrier (BRB) can mitigate deleterious immune response. Dysfunction at the BRB can affect disease progression. Under inflammatory conditions Müller glia produce increased pro-inflammatory factors, like nitric oxide (NO). ⋯ Exogenous arachidonoyl ethanolamide (AEA) inhibited NO generation and also abolished LPS-induced increase in permeability. Our work suggests that subtle changes in Müller glia function, which act as part of the BRB, could contribute to retinal health. AEA which can reduce inflammatory cytotoxicity has potential as treatment in several ocular manifestations where the integrity of the BRB is crucial.
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Oxidative stress and apoptosis were induced in neuronal cultures by inhibition of glutathione (GSH) biosynthesis with d,l-buthionine-S,R-sulfoximine (BSO). Transient receptor potential melastatin 2 (TRPM2) and transient receptor potential vanilloid 1 (TRPV1) cation channels are gated by oxidative stress. The oxidant effects of homocysteine (Hcy) may induce activation of TRPV1 and TRPM2 channels in aged mice as a model of Alzheimer's disease (AD). ⋯ Inhibitor roles of 2-APB and capsazepine on the Ca2+ entry higher than in V+D and MK-801 antagonists. In conclusion, these findings support the idea that GSH depletion and Hcy elevation can have damaging effects on hippocampal neurons by perturbing calcium homeostasis, mainly through TRPM2 and TRPV1 channels. GSH treatment can partially reverse these effects.
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Deciphering the molecular pathways involved in myelin gene expression is a major point of interest to better understand re/myelination processes. In this study, we investigated the role of Lithium Chloride (LiCl), a drug largely used for the treatment of neurological disorders, on the two major central myelin gene expression (PLP and MBP) in mouse oligodendrocytes. We show that LiCl enhances the expression of both PLP and MBP, by increasing mRNA amount and promoter activities. ⋯ Finally, we show that LiCl can stimulate oligodendrocyte morphological maturation, and promote remyelination after lysolecithin-induced demyelination of organotypic cerebellar slice cultures. Our data provide mechanistic evidences that Akt/CREB together with β-catenin participate in the transcriptional control of PLP and MBP exerted by LiCl. Therefore, the use of LiCl to balance between β-catenin and CREB effectors could be considered as an efficient remyelinating strategy.