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000276824 1001_ $$0P:(DE-2719)9000779$$aStrackeljan, Luisa$$b0$$eFirst author$$udzne
000276824 245__ $$aPartial microglial depletion through inhibition of colony-stimulating factor 1 receptor improves synaptic plasticity and cognitive performance in aged mice.
000276824 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2025
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000276824 520__ $$aMicroglia 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.
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000276824 650_7 $$2Other$$aAging
000276824 650_7 $$2Other$$aBrevican
000276824 650_7 $$2Other$$aExtracellular matrix
000276824 650_7 $$2Other$$aGlia
000276824 650_7 $$2Other$$aParvalbumin
000276824 650_7 $$2Other$$aPerineuronal nets
000276824 650_7 $$2Other$$aPerisynaptic ECM
000276824 650_7 $$2Other$$aSynapses
000276824 7001_ $$0P:(DE-2719)9001469$$aBaidoe-Ansah, David$$b1$$udzne
000276824 7001_ $$0P:(DE-2719)2814120$$aMirzapourdelavar, Hadi$$b2$$udzne
000276824 7001_ $$0P:(DE-2719)2811420$$aJia, Shaobo$$b3$$udzne
000276824 7001_ $$0P:(DE-2719)2811394$$aKaushik, Rahul$$b4
000276824 7001_ $$0P:(DE-2719)9001455$$aCangalaya, Carla$$b5$$udzne
000276824 7001_ $$0P:(DE-2719)2810577$$aDityatev, Alexander$$b6$$eLast author$$udzne
000276824 773__ $$0PERI:(DE-600)1466932-8$$a10.1016/j.expneurol.2025.115186$$gVol. 387, p. 115186 -$$p115186$$tExperimental neurology$$v387$$x0014-4886$$y2025
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