Neuroscience
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Although the mechanisms underlying dystonia are largely unknown, dystonia is often associated with abnormal dopamine neurotransmission. DOPA-responsive dystonia (DRD) is a prototype disorder for understanding dopamine dysfunction in dystonia because it is caused by mutations in genes necessary for the synthesis of dopamine and alleviated by the indirect-acting dopamine agonist l-DOPA. Although adaptations in striatal dopamine receptor-mediated intracellular signaling have been studied extensively in models of Parkinson's disease, another movement disorders associated with dopamine deficiency, little is known about dopaminergic adaptations in dystonia. ⋯ The D2 dopamine receptor antagonist raclopride also significantly reduced the phosphorylation of ERK; this contrasts with models of parkinsonism in which l-DOPA-induced ERK phosphorylation is not mediated by D2 dopamine receptors. Further, the dysregulated signaling was dependent on striatal subdomains whereby ERK phosphorylation was largely confined to dorsomedial (associative) striatum while the dorsolateral (sensorimotor) striatum was unresponsive. This complex interaction between striatal functional domains and dysregulated dopamine-receptor mediated responses has not been observed in other models of dopamine deficiency, such as parkinsonism, suggesting that regional variation in dopamine-mediated neurotransmission may be a hallmark of dystonia.
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Sepsis-associated encephalopathy (SAE) is a common neurological complication of sepsis and is characterized by hyperneuroinflammation. NLRP3 inflammasome-mediated pyroptosis can induce an inflammatory cascade response and plays a key role in SAE. TRPV4 is involved in the hyperinflammatory response associated with inflammation; however, whether TRPV4 inhibition might alleviate SAE-related brain damage is still unknown. ⋯ The disruption of BBB integrity in SAE mice was also rescued by HC067047 intervention. Thus, we can conclude that the TRPV4 inhibitor HC067047 could protect against hippocampal cell pyroptosis, which might be due to the attenuation of the NLRP3 inflammasome-mediated pyroptosis pathway caused by ER stress and OS. Our findings suggest a potential preventive role for HC067047 in SAE.
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The purpose of the study was to investigate the effect of isoflurane postconditioning on neuron injury in MCAO (middle cerebral artery occlusion) rats and its molecular mechanism of affecting autophagy through miR-384-5p/ATG5 (autophagy-related protein 5). HT22 cells (mouse hippocampal neuronal cell line) were exposed to 1.5% isoflurane for 30 min after OGD/R (oxygen-glucose deprivation/reoxygenation). Flow cytometry and CCK-8 kit were used to analyze changes in apoptosis and cell viability. ⋯ TUNEL staining and western blot results confirmed that isoflurane post-conditioning could regulate miR-384-5p and inhibit apoptosis. Immunofluorescence staining and western blot results confirmed that isoflurane post-conditioning inhibited autophagy in MCAO rats. Based on the above results, we speculated that the molecular mechanism of isoflurane post-conditioning to alleviate ischemic neuronal injury may be related to the regulation of miR-384-5p/ATG5-mediated autophagy.
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Gonadal hormones are becoming increasingly recognized for their effects on cognition. Estrogens, in particular, have received attention for their effects on learning and memory that rely upon the functioning of various brain regions. However, the impacts of androgens on cognition are relatively under investigated. ⋯ We highlight the relevance of considering not only the actions of the most commonly studied steroids (i.e., testosterone, 17β-estradiol, and dihydrotestosterone), but also that of their metabolites and precursors, which interact with a plethora of different receptors and signalling molecules, ultimately modulating behaviour. We point out that it is also essential to investigate the effects of androgens, their precursors and metabolites in females, as prior studies have mostly focused on males. Overall, a comprehensive analysis of the impact of steroids such as androgens on behaviour is fundamental for a full understanding of the neural mechanisms underlying social cognition, including that of humans.
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Walking is an important function which requires coordinated activity of sensory-motor neural networks. Noninvasive brain stimulation (NIBS) is a safe neuromodulatory technique with motor function-improving effects. This study aimed to determine the effect of different types of NIBS interventions explored in randomized controlled trials on gait in healthy young and older adults. ⋯ NIBS is a promising approach to improve gait in healthy young and older adults. Anodal tDCS over the motor areas and DLPFC, and tACS over the cerebellum have shown positive effects on gait.