A multimodal approach of microglial CSF1R inhibition and GENUS provides therapeutic effects in Alzheimer's disease mice.

ABSTRACT: The CSF1R inhibitor PLX3397, an FDA-approved treatment for a rare cancer, has been shown to reduce microglia count, lower inflammation, and increase synaptic markers in mouse models of Alzheimer's disease (AD). However, the effects of PLX3397 on neural function in AD remain largely unknown. Here, we characterized the effects of PLX3397 treatment in 5xFAD mice. While PLX3397 increased synaptic density, it reduced the percentage of neurons phase-locked to gamma oscillations. This neural decoupling was closely associated with gene expression changes related to synapse organization. We investigated whether Gamma ENtrainment Using Sensory (GENUS) stimulation could counterbalance the neural circuit alterations induced by PLX3397. GENUS + PLX3397 restored gamma phase-locking, reshaped gene expres

SUBMITTER: Adaikkan C 

PROVIDER: S-EPMC12338498 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature