Regeneration of myelin by adult neural stem cells using rodent models of neurological diseases
The myelin sheath is a specialized membrane synthesized by oligodendrocytes, which wraps around the axons of neurons in the vertebrate brain. Myelin is lost in normal aging as well as in several neurological diseases which include Multiple Sclerosis, Alzheimer’s disease, and Schizophrenia. In demyelinating diseases, disruption of myelin results in severe neurological deficits due to conduction block leading to the loss of axons and ultimately neurodegeneration. The goal in treating neurological diseases with myelin loss is to remyelinate the demyelinated axons before the neurons degenerate.
Our lab focuses on how neural stem cells regenerate myelin following demyelination. Our objective is to understand the molecular mechanisms underlying proliferation, migration and differentiation of neural stem cells into myelinating oligodendrocytes to help develop therapeutic strategies for remyelination.
Live imaging of primary adult neural stem cells showing migration and cell division of Gli1 neural stem cell (red) along with neural stem cells infected with GFP-lentivirus (green)
SELECTED PUBLICATIONS
*Radecki DZ, Wang AR, Johnson AS, Overman CA, Thatcher MM, Iyer G, Samanta J. Gpnmb inhibits oligodendrocyte differentiation of neural stem cells by amplifying TGFβ1 signaling. bioRxiv 2021.08.13.456269, in revision Nature Communications.
*Doss GA, Radecki DZ, Kethiredy A, Reilly MJ, Pohly AE, August BK, Duncan ID, Samanta J (2023). Wobbly Hedgehog Syndrome- a progressive neurodegenerative disease, Experimental Neurology, PMID:37634698
*Clawson ED, Radecki DZ, Samanta J (2023). Immunofluorescence assay for demyelination, remyelination, and proliferation in an acute cuprizone mouse STAR Protocols, PMID: 36853716
*Radecki DZ, Samanta J (2022). Endogenous neural stem cell mediated oligodendrogenesis in the adult mammalian brain. Invited review, Cells, PMID: 35805185
*Radecki DZ, Samanta J (2022). Isolation and culture of neural stem cells from adult mouse subventricular zone for genetic and pharmacological treatments with proliferation STAR Protocols, PMID: 35146452
*Samanta J, Silva HM, Lafaille JJ, Salzer JL* (2021). Transcriptomic analysis of loss of Gli1 in neural stem cells responding to demyelination in the mouse brain. Scientific Data, PMID: 34711861
*Radecki DZ, Messling H, Haggerty-Skeans JR, Bhamidipati SK, Clawson ED, Overman CA, Thatcher MM, Salzer JL, Samanta J (2020). Relative levels of Gli1 and Gli2 determine the response of ventral neural stem cells to demyelination, Stem Cell Reports, PMID: 33125874
*Samanta J, Grund EM, Silva HM, Lafaille JJ, Fishell G, Salzer JL (2015). Inhibition of Gli1 mobilizes endogenous neural stem cells for Nature, PMID: 26416758
