Journal Article

DZNE-2025-00337

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Partial microglial depletion through inhibition of colony-stimulating factor 1 receptor improves synaptic plasticity and cognitive performance in aged mice.

Strackeljan, L. (First author)DZNE* ; Baidoe-Ansah, D.DZNE* ; Mirzapourdelavar, H.DZNE* ; Jia, S.DZNE* ; Kaushik, R.DZNE* ; Cangalaya, C.DZNE* ; Dityatev, A. (Last author)DZNE*

2025
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.expneurol.2025.115186

Abstract: Microglia depletion, followed by repopulation, improves cognitive functions in the aged mouse brain. However, even temporal ablation of microglia puts the brain at a high risk of infection. Hence, in the present work, we studied if the partial reduction of microglia with PLX3397 (pexidartinib), an inhibitor of the colony-stimulating factor 1 receptor (CSF1R), could bring similar benefits as reported for microglia ablation. Aged (two-years-old) mice were treated with PLX3397 for a total of 6 weeks, which reduced microglia numbers in the hippocampus and retrosplenial cortex (RSC) to the levels seen in young mice and resulted in layer-specific ablation in the expression of microglial complement protein C1q mediating synaptic remodeling. This treatment boosted long-term potentiation in the CA1 region and improved performance in the hippocampus-dependent novel object location recognition task. Although PLX3397 treatment did not alter the number or total intensity of Wisteria floribunda agglutinin-positive perineuronal nets (PNNs) in the CA1 region of the hippocampus, it changed the fine structure of PNNs. It also elevated the expression of perisynaptic proteoglycan brevican, presynaptic vGluT1 at excitatory synapses, and vGAT in inhibitory ones in the CA1 stratum radiatum. Thus, targeting the CSF1R may provide a safe and efficient strategy to boost synaptic and cognitive functions in the aged brain.

Keyword(s): Aging ; Brevican ; Extracellular matrix ; Glia ; Parvalbumin ; Perineuronal nets ; Perisynaptic ECM ; Synapses

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Contributing Institute(s):

1. Molecular Neuroplasticity (AG Dityatev)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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