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- W2970843204 abstract "Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite effective antiretroviral therapies (ART). Evidence suggests that modern HAND is driven by subtle synaptodendritic damage in select brain regions, as ART-treated patients do not display overt neuronal death in postmortem brain studies. HAND symptoms are also aggravated by drug abuse, particularly with injection opioids. Opioid use produces region-specific synaptodendritic damage in similar brain regions, suggesting a convergent mechanism that may enhance HAND progression in opioid-using patients. Importantly, studies indicate that synaptodendritic damage and cognitive impairment in HAND may be reversible. Activation of the homeostatic chemokine receptor CXCR4 by its natural ligand CXCL12 positively regulates neuronal survival and dendritic spine density in cortical neurons, reducing functional deficits. However, the molecular mechanisms that underlie CXCR4, as well as opioid-mediated regulation of dendritic spines are not completely defined. Here, we will consolidate studies that describe the region-specific synaptodendritic damage in the cerebral cortex of patients and animal models of HAND, describe the pathways by which opioids may contribute to cortical synaptodendritic damage, and discuss the prospects of using the CXCR4 signaling pathway to identify new approaches to reverse dendritic spine deficits. Additionally, we will discuss novel research questions that have emerged from recent studies of CXCR4 and µ-opioid actions in the cortex. Understanding the pathways that underlie synaptodendritic damage and rescue are necessary for developing novel, effective therapeutics for this growing patient population." @default.
- W2970843204 created "2019-09-05" @default.
- W2970843204 creator A5058154140 @default.
- W2970843204 creator A5060756668 @default.
- W2970843204 creator A5074891027 @default.
- W2970843204 creator A5087964642 @default.
- W2970843204 date "2019-11-01" @default.
- W2970843204 modified "2023-10-15" @default.
- W2970843204 title "Opioid and chemokine regulation of cortical synaptodendritic damage in HIV-associated neurocognitive disorders" @default.
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