Oleic acid triggers hippocampal neurogenesis by binding to TLX/NR2E1

Prasanna Kandel; Fatih Semerci; Aleksandar Bajić; Dodge L. Baluya; Lihua Ma; Kevin C. Chen; Austin C. Cao; Tipwarin Phongmekhin; Nick Matinyan; William Tin-Shing Choi; Alba Jiménez‐Panizo; Srinivas Chamakuri; Idris O. Raji; Lyra Chang; Pablo Fuentes‐Prior; Kevin R. MacKenzie; Caroline Benn; Eva Estébanez‐Perpiñá; Koen J. T. Venken; David D. Moore; Damian W. Young; Mirjana Maletić‐Savatić

doi:10.1101/2020.10.28.359810

NeurosciencebioRxivOct 28, 2020

Preprint

Oleic acid triggers hippocampal neurogenesis by binding to TLX/NR2E1

Prasanna Kandel iD, Fatih Semerci iD, Aleksandar Bajić iD, Dodge L. Baluya iD, Lihua Ma iD, Kevin C. Chen iD, Austin C. Cao iD, Tipwarin Phongmekhin iD, Nick Matinyan iD, William Tin-Shing Choi, Alba Jiménez‐Panizo iD, Srinivas Chamakuri iD, Idris O. Raji iD, Lyra Chang iD, Pablo Fuentes‐Prior iD, Kevin R. MacKenzie iD, Caroline Benn, Eva Estébanez‐Perpiñá iD, Koen J. T. Venken iD, David D. Moore iD, Damian W. Young iD, Mirjana Maletić‐Savatić iD

Abstract

Adult hippocampal neurogenesis underpins learning, memory, and mood, but diminishes with age and illness. The orphan nuclear receptor TLX/NR2E1 is known to regulate neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is unknown. We found that neural stem and progenitor cells require monounsaturated fatty acids to survive and proliferate. Specifically, oleic acid (18:1{omega}9) binds to TLX to convert it from a transcriptional repressor to a transcriptional activator of cell cycle and neurogenesis genes. We propose a model in which sufficient quantities of this endogenous ligand must bind to TLX to trigger the switch to proliferation. These findings pave the way for future therapeutic manipulations to counteract pathogenic impairments of neurogenesis.

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