A Chemical-genetic Investigation of BDNF-NtrkB Signaling in Mammalian Sleep

Overview

Journal Sleep

Publisher Oxford University Press

Specialty Psychiatry

Date 2021 Sep 19

PMID 34537852

Citations 5

Authors

Christine M Muheim

Kristan G Singletary

Marcos G Frank

Affiliations

Soon will be listed here.

Abstract

Study Objectives: The neurotrophin brain-derived neurotrophic factor (BDNF) is hypothesized to be a molecular mediator of mammalian sleep homeostasis. This hypothesis is supported by correlational findings and results obtained from pharmacology. BDNF binds with high affinity to the membrane-bound receptor Neurotrophin Tyrosine Kinase Receptor B (NtrkB), which triggers several intracellular signaling cascades. It is therefore possible that BDNF's role in sleep homeostasis is mediated via NtrkB. We examined this hypothesis using a chemical-genetic technique that allows for rapid and selective inhibition of NtrkB in vivo.

Methods: We used mutant mice bearing a point mutation in the NtrkB that allows for selective and reversible inactivation in the presence of a small binding molecule (1-NM-PP1). Using a crossover design, we determined the effects of NtrkB inhibition on baseline sleep architecture and sleep homeostasis.

Results: We find that NtrkB inhibition reduced rapid eye movement (REM) sleep time and changed state transitions but had no effect on sleep homeostasis.

Conclusions: These findings suggest that BDNF-NtrkB receptor signaling has subtle roles in sleep architecture, but no role in sleep homeostasis.

Citing Articles

Dynamic changes in cortical neurotrophic factor-positive interneurons during sleep.

Muheim C, Frank M Sci Rep. 2025; 15(1):6403.

PMID: 39984617 PMC: 11845688. DOI: 10.1038/s41598-025-90878-4.

Investigating the Role of BDNF in Insomnia: Current Insights.

Ditmer M, Gabryelska A, Turkiewicz S, Sochal M Nat Sci Sleep. 2023; 15:1045-1060.

PMID: 38090631 PMC: 10712264. DOI: 10.2147/NSS.S401271.

Ontogenesis of the molecular response to sleep loss.

Muheim C, Ford K, Medina E, Singletary K, Peixoto L, Frank M Neurobiol Sleep Circadian Rhythms. 2023; 14:100092.

PMID: 37020466 PMC: 10068260. DOI: 10.1016/j.nbscr.2023.100092.

Ontogenesis of the molecular response to sleep loss.

Muheim C, Ford K, Medina E, Singletary K, Peixoto L, Frank M bioRxiv. 2023; .

PMID: 36712085 PMC: 9882159. DOI: 10.1101/2023.01.16.524266.

Brain-derived neurotrophic factor Val66Met polymorphism modulates the effects of circadian desynchronization on activity and sleep in male mice.

Phillips D, Blaine S, Wallace N, Karatsoreos I Front Neurosci. 2023; 16:1013673.

PMID: 36699530 PMC: 9868941. DOI: 10.3389/fnins.2022.1013673.

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