Oligodendrocytes are critical for CNS myelin formation and are involved in preterm-birth brain injury (PBI) and multiple sclerosis (MS), both of which lack effective treatments. We present a pharmacogenomic approach that identifies compounds with potent pro-oligodendrogenic activity, selected through a scoring strategy (OligoScore) based on their modulation of oligodendrogenic and (re)myelination-related transcriptional programs. Through in vitro neural and oligodendrocyte progenitor cell (OPC) cultures, ex vivo cerebellar explants, and in vivo mouse models of PBI and MS, we identify FDA-approved leucovorin and dyclonine as promising candidates.
View Article and Find Full Text PDFExercise promotes learning and memory recall as well as rescues cognitive decline associated with aging. The positive effects of exercise are mediated by circulatory factors that predominantly increase Brain Derived Neurotrophic Factor (BDNF) signaling in the hippocampus. Identifying the pathways that regulate the release of the circulatory factors by various tissues during exercise and that mediate hippocampal expression will allow us to harness the therapeutic potential of exercise.
View Article and Find Full Text PDFThe proneural transcription factor Achaete-scute complex-like 1 (Ascl1) is a major regulator of neural fate decisions, implicated both in neurogenesis and oligodendrogliogenesis. Focusing on its neurogenic activity, Ascl1 has been widely used to reprogram non-neuronal cells into induced neurons. , Ascl1 induces efficient reprogramming of proliferative astroglia from the early postnatal cerebral cortex into interneuron-like cells.
View Article and Find Full Text PDFThe term "neural plasticity" was first used to describe non-pathological changes in neuronal structure. Today, it is generally accepted that the brain is a dynamic system whose morphology and function is influenced by a variety of factors including stress, diet, and exercise. Neural plasticity involves learning and memory, the synthesis of new neurons, the repair of damaged connections, and several other compensatory mechanisms.
View Article and Find Full Text PDFThe purpose of this study was to investigate how nicotine in the context of water pipe tobacco smoking (WTS) affects depression and anxiety-like behaviors associated with chronic social defeat stress (CSDS). Male C57BL/6 J mice were exposed to WTS or received intraperitoneal injections of nicotine for thirty days then subjected to CSDS for ten days. During CSDS, mice were exposed to WTS or received nicotine injections.
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