Neuroscience
-
Ferroptosis plays a key role in the process of spinal cord injury (SCI). As a signal amplifier, connexin 43 (CX43) participates in cell death signal transduction and aggravates the propagation of injury. However, it remains unclear whether CX43 plays a regulatory role in ferroptosis after SCI. ⋯ As a result, the levels of GPX4 and glutathione (GSH) increased, while the levels of the lipid peroxidation products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) decreased. Together, inhibition of CX43 could alleviate ferroptosis after SCI. These findings reveal a potential mechanism of the neuroprotective role of CX43 after SCI and provide a new theoretical basis for clinical transformation and application.
-
Over half of all stroke patients present gastrointestinal complications. It has been speculated that there is an intriguing brain-gut connection. However, molecular mechanisms of the connection remain poorly illuminated. ⋯ In conclusion, we have demonstrated that the proteins and metabolites in the colon are significantly changed after ischemic stroke, which provides molecular-level evidence regarding the brain-gut connection. In this light, several common enriched pathways of DEPs may become potential therapeutic targets for stroke upon the brain-gut axis. Notably, we have discovered a promising colon-derived metabolite enterolactone possibly beneficial for tackling stroke.
-
Although hypoxic postconditioning (HPC) has a protective effect on ischemic stroke, its effect on angiogenesis after ischemic stroke is still unclear. This study was designed to investigate the effects of HPC on angiogenesis after ischemic stroke and to preliminarily study the mechanism involved. Oxygen-glucose deprivation (OGD)-intervened bEnd.3 (mouse brain-derived Endothelial cell. 3) was used to simulate cerebral ischemia. ⋯ The HPC mice showed higher PLCλ and ALK5 than did MCAO. We conclude that HPC improves the neurological deficit caused by focal cerebral ischemia by promoting angiogenesis. Furthermore, the effect of HPC on improving angiogenesis may be related to PLCλ and ALK5.
-
Parkinson's Disease is a synucleinopathy that primarily affects the dopaminergic cells of the central nervous system, leading to motor and gastrointestinal disturbances. However, intestinal peripheral neurons undergo a similar neurodegeneration process, marked by α-synuclein (αSyn) accumulation and loss of mitochondrial homeostasis. We investigated the metabolic alterations in different biometrics that compose the gut-brain axis (blood, brain, large intestine, and feces) in an MPTP-induced mouse model of sporadic Parkinson's Disease. ⋯ The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. This data reinforces previous studies showing that Parkinson's disease is associated with metabolic perturbation not only in brain-related tissues, but also in periphery structures such as the gut. In addition, the evaluation of the microbiome and metabolites from gut and feces emerge as promising sources of information for understanding the evolution and progression of sporadic Parkinson's Disease.
-
GPR81 is a G-protein coupled receptor (GPCR) discovered in 2001, but deorphanized only 7 years later, when its affinity for lactate as an endogenous ligand was demonstrated. More recently, GPR81 expression and distribution in the brain were also confirmed and the function of lactate as a volume transmitter has been suggested since then. These findings shed light on a new function of lactate acting as a signaling molecule in the central nervous system, in addition to its well-known role as a metabolic fuel for neurons. ⋯ The activation of GPR81 showed promising results for neuroprotection: it modulates many processes involved in the pathophysiology of ischemia. In this review, we summarize the history of GPR81, starting with its deorphanization; then, we discuss GPR81 expression and distribution, signaling transduction cascades, and neuroprotective roles. Lastly, we propose GPR81 as a potential target for the treatment of cerebral ischemia.