Myeloid Deficiency of the Intrinsic Clock Protein BMAL1 Accelerates Cognitive Aging by Disrupting Microglial Synaptic Pruning

Overview

Journal J Neuroinflammation

Publisher Biomed Central

Date 2023 Feb 24

PMID 36829230

Authors

Chinyere Agbaegbu Iweka

Erica Seigneur

Amira Latif Hernandez

Sur Herrera Paredes

Mica Cabrera

Eran Blacher

Connie Tsai Pasternak

Frank M Longo

Luis De Lecea

Katrin I Andreasson

Affiliations

Soon will be listed here.

Abstract

Aging is associated with loss of circadian immune responses and circadian gene transcription in peripheral macrophages. Microglia, the resident macrophages of the brain, also show diurnal rhythmicity in regulating local immune responses and synaptic remodeling. To investigate the interaction between aging and microglial circadian rhythmicity, we examined mice deficient in the core clock transcription factor, BMAL1. Aging Cd11b;Bmal mice demonstrated accelerated cognitive decline in association with suppressed hippocampal long-term potentiation and increases in immature dendritic spines. C1q deposition at synapses and synaptic engulfment were significantly decreased in aging Bmal1-deficient microglia, suggesting that BMAL1 plays a role in regulating synaptic pruning in aging. In addition to accelerated age-associated hippocampal deficits, Cd11b;Bmal mice also showed deficits in the sleep-wake cycle with increased wakefulness across light and dark phases. These results highlight an essential role of microglial BMAL1 in maintenance of synapse homeostasis in the aging brain.

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