Neuroscience
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Genetic factors significantly contribute to the risk for developing alcoholism. To study these factors and other associated phenotypes, rodent lines have been developed using selective breeding for high alcohol preference. One of these models, the alcohol preferring (P) rat, has been used in hundreds of preclinical studies over the last few decades. ⋯ Intra-CeA infusion of NK1R antagonist attenuates yohimbine-induced reinstatement in P rats. Conversely, upregulation of NK1R within the CeA of Wistar rats increases alcohol consumption and sensitivity to yohimbine-induced reinstatement. These findings suggest that NK1R upregulation in the CeA contributes to multiple alcohol-related phenotypes in the P rat, including alcohol consumption and sensitivity to relapse.
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Radial glial maintenance is essential for the proper development of the cortex. It is known that the evolutionarily conserved Notch signaling pathway is required for maintaining the pool of radial glial stem cells although the mechanisms involved are not entirely understood. Here, we study the Notch ligand, Jagged1, in the mouse ventricular zone at a late stage of embryonic development. ⋯ Using in vitro approaches, we found that depletion of Jagged1 reduced the size of primary neurospheres and their capacity to self-renewal. Finally, Jagged1 mutants also showed precocious neuronal differentiation and cortical defects. Together, these data support a role for Jagged1 in radial glia maintenance in the neocortex.
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Leucine-rich α2-glycoprotein1 (LRG1), a pleiotropic protein, plays a pathogenic role in multiple human diseases. However, its pathophysiological function in ischemia/reperfusion injury remains unclear. In this study, we discussed the function and mechanism of LRG1 in acute ischemic stroke from both basic and clinical research points of view. ⋯ We also showed that patients with acute cerebral infarction had lower serum levels of LRG1 compared to healthy controls. In addition, LRG1 levels were associated with infarction volume, stroke severity, and prognosis in patients with supratentorial infarction. Taken together, the data from this study revealed that LRG1 promoted apoptosis and autophagy through the TGFβ-smad1/5 signaling pathway by up-regulating ALK1, which exacerbates ischemia/reperfusion injury.
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Few animal studies focus on consequences of nicotine postnatal exposure, particularly through lactation. We have recently shown that forced nicotine drinking elevates maternal care, paradoxically provoking arousal and stress in pups. Present work aimed to evaluate the specific contribution of altered maternal cares, compared to the sequelae merely due to nicotine effects. ⋯ Brain analyses at adulthood suggest that, in prefrontal cortex, nicotine per se reduced serotonin, while the maternal overcare reduced CHRN-B2 gene-expression. As a whole, unescapable nicotine-enhanced maternal care could have an impact on the offspring arousal by acting on prefrontal CHRN-B2 gene-expression. When present results are translated to consequences of non-voluntary exposure in humans, we propose that children receiving altered attentions by a smoking caregiver might undergo a neuro-behavioural development biased towards emotional shyness.
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Nicotinic acetylcholine receptors of α7 subtype (α7 nAChRs) are involved in regulating cognition, inflammation and cell survival. Neuroinflammation is accompanied by the decrease of α7 nAChRs in the brain and impairment of memory. We show here that α7-/- mice possess pro-inflammatory phenotype and demonstrate worse episodic memory compared to wild-type mice. ⋯ It is concluded that MSCs, injected intravenously, penetrate the brain of α7-/- mice and persist there for at least 2 weeks. They improve episodic memory of mice and make their mitochondria more resistant to apoptogenic influence. One of the soluble factors responsible for the memory improvement is IL-6.