Impact on Endogenous Neural Stem Cells and Neurogenesis by Drugs of Abuse: From Fetal Neurodevelopment to the Adult Brain

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Neural stem cells (NSCs) are a subpopulation of cells, found within the fetal and adult brain, that are integral to brain development, maintenance, and repair. Neurogenesis is the process through which NSCs proliferate and differentiate to create new neural cells within the central nervous system. These cells are vulnerable to drugs of abuse by decreasing self-renewal and subsequent differentiation, during adult or prenatal exposure. Recently, there has been an increase in the number of prescriptions written for opioids, leading to the current opioid epidemic. Further, prescription opioid use by women during pregnancy has risen dramatically since 2004. This rise was accompanied by a striking increase in the prevalence of neonatal opioid withdrawal syndrome and other long-term neurological deficits. Some of these drugs of abuse also include cocaine and alcohol, and the combination of which is the third leading cause of drug overdose deaths in the United States. While the effects of cocaine and alcohol, individually, on NSCs has been studied, the combined effects, whether additive or synergistic, remains unknown. This dissertation aimed to examine the effects of drugs of abuse on endogenous neural stem cells and neurogenesis in two translationally relevant novel murine models of substance use; in the developing and adult brain.

Neurogenesis, Drugs of Abuse, Development, Adult