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Quantitative synaptic proteomics analysis reveal OTX1 regulates complement-dependent microglia-mediated synaptic pruning in the cerebral cortex of Otx1 mutant mouse

ABSTRACT: The mammalian cortex is the structural basis for learning, cognition, and movement coordination. Dysgenesis of axon dendrites and synapses in cortical neurons can hinder learning and cognitive development, leading to epilepsy. Transcription factor Otx1 plays an important role in the development of the morphology and electrophysiological activity of cortical neurons and is associated with the occurrence of epilepsy. Abnormal synaptic pruning has been proposed to be one of the molecular mechanisms underlying epilepsy. Otx1 mutant mice leads to defective axonal pruning and changes the excitability and synaptic connections of the cortical neurons. However, little is known about the molecular pathways through which the loss of Otx1 causes epilepsy. On this basis, we found that the density and morphology of dendritic spines and microglia in Otx1 mutant mice changed significantly. TMT analysis of synaptic proteins reveals that Otx1 regulates the structure and function of cortical neurons and synaptic characteristics by regulating microglia-mediated synaptic pruning through the complement system, which also has important theoretical significance and application value for effective prevention and treatment of epilepsy.

ORGANISM(S): Mus Musculus

SUBMITTER: Chao Wang

PROVIDER: PXD041568 | iProX | Sat Apr 15 00:00:00 BST 2023

REPOSITORIES: iProX

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Quantitative synaptic proteomics analysis reveal OTX1 regulates complement-dependent microglia-mediated synaptic pruning in the cerebral cortex of Otx1 mutant mouse

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