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p75NTR Regulates Oligodendrocyte Progenitor Development in the SubventricularZone of Postnatal Rats

Award Number: R21NS137258
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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p75NTR Regulates Oligodendrocyte Progenitor Development in the SubventricularZone of Postnatal Rats - Summary Generating the appropriate numbers of cells in a particular lineage is critical for normal development of the brain. Progenitor cells of both neuronal and glial lineages are present in the postnatal subventricular zone (SVZ) of rats, with a period of gliogenesis that is maximal during the first two postnatal weeks. We find that the p75 neurotrophin receptor (p75NTR) is abundantly expressed in intermediate progenitor cells in the rat SVZ. Deletion of this receptor elicits an overproduction of oligodendrocyte lineage cells and precocious maturation of these cells with abnormal myelin development during the early stages of myelination, suggesting that p75NTR normally acts to restrict premature differentiation of oligodendrocyte lineage cells. This expression of p75NTR in the SVZ has been observed in rat and human, but not mouse, and we suggest that this may be a mechanism that evolved to regulate the timing and balance between generating cells of a particular lineage while maintaining a pool of progenitor cells in an immature state. We will create a cell-specific rat line to delete p75NTR (p75NTRfl/fl) specifically in oligodendrocyte progenitors (PDGFRa-CreERT2), and use this line as well as the global p75NTR KO rats to investigate mechanisms by which p75NTR regulates oligodendrocyte differentiation and maturation. Additionally, we will determine whether deletion of p75NTR impacts the persistence of the oligodendrocyte progenitor pool in the SVZ. We will assess whether the altered regulation of oligodendrocyte progenitors during development in the p75NTR KO rats impacts the ability to remyelinate after a demyelinating lesion in adult rats.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $196,250 )
2025	2025	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/9/2025	NON-COMPETING CONTINUATION	$196,250
														Subtotal = $196,250

Issue Date FY: 2024 ( Subtotal = $235,500 )
2024	2024	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/1/2024	NEW	$235,500
														Subtotal = $235,500

Grand Total All Awards = $431,750

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p75NTR Regulates Oligodendrocyte Progenitor Development in the SubventricularZone of Postnatal Rats

Award Number: R21NS137258

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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