Academic Commons

Articles

RbAp48 Protein Is a Critical Component of GPR158/OCN Signaling and Ameliorates Age-Related Memory Loss

Kosmidis, Stylianos; Polyzos, Alexandros; Harvey, Lucas; Youssef, Mary T.; Denny, Christine Ann; Dranovsky, Alex; Kandel, Eric

Precisely deciphering the molecular mechanisms of age-related memory loss is crucial to create appropriate therapeutic interventions. We have previously shown that the histone-binding protein RbAp48/Rbbp4 is a molecular determinant of Age-Related Memory Loss. By exploring how this protein regulates the genomic landscape of the hippocampal circuit, we find that RbAp48 controls the expression of BDNF and GPR158 proteins, both critical components of osteocalcin (OCN) signaling in the mouse hippocampus. We show that inhibition of RbAp48 in the hippocampal formation inhibits OCN’s beneficial functions in cognition and causes deficits in discrimination memory. In turn, disruption of OCN/GPR158 signaling leads to the downregulation of RbAp48 protein, mimicking the discrimination memory deficits observed in the aged hippocampus. We also show that activation of the OCN/GPR158 pathway increases the expression of RbAp48 in the aged dentate gyrus and rescues age-related memory loss.

Files

  • thumnail for 1-s2.0-S2211124718315377-main.pdf 1-s2.0-S2211124718315377-main.pdf application/pdf 5.04 MB Download File

Also Published In

More About This Work

Academic Units
Neuroscience
Psychiatry
Zuckerman Mind Brain Behavior Institute
Published Here
November 8, 2018
Academic Commons provides global access to research and scholarship produced at Columbia University, Barnard College, Teachers College, Union Theological Seminary and Jewish Theological Seminary. Academic Commons is managed by the Columbia University Libraries.