Why Some Mice Are Smarter Than Others: The Impact of Bone Morphogenetic Protein Signaling on Cognition

Overview

Journal eNeuro

Specialty Neurology

Date 2023 Jan 3

PMID 36596594

Authors

Jacqueline A Bonds

Elif Tunc-Ozcan

Sara R Dunlop

Radhika Rawat

Chian-Yu Peng

John A Kessler

Affiliations

Soon will be listed here.

Abstract

Inbred mice (C57Bl/6) display wide variability in performance on hippocampal-dependent cognitive tasks. Examination of microdissected dentate gyrus (DG) after cognitive testing showed a highly significant negative correlation between levels of bone morphogenetic protein (BMP) signaling and recognition memory. Cognitive performance decline during the aging process, and the degree of cognitive decline is strongly correlated with aging-related increases in BMP signaling. Further, cognitive performance was impaired when the BMP inhibitor, noggin, was knocked down in the DG. Infusion of noggin into the lateral ventricles enhanced DG-dependent cognition while BMP4 infusion led to significant impairments. Embryonic overexpression of noggin resulted in lifelong enhancement of recognition and spatial memory while overexpression of BMP4 resulted in lifelong impairment, substantiating the importance of differences in BMP signaling in wild-type mice. These findings indicate that performance in DG-dependent cognitive tasks is largely determined by differences in levels BMP signaling in the dentate gyrus.

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