CD200 dysfunction in neuron contributes to synaptic deficits and cognitive impairment

Neuronal CD200 plays critical role in neuron-microglia communication and negatively related to pathological development of Alzheimer's disease, but its contribution retroacts to synaptic function is still not clear. Here, we directly injected adeno-associated virus into hippocampus of APP/PS1 mice to induce neuron-specific CD200 overexpression; subsequently, we detected cognition function, synaptic function, and the microglial responses during AD pathological development. Notably, specific upregulation of neuronal CD200 promoted cognitive function by inhibiting microglial activation and secretion, improving synaptic function, and preventing synaptic loss. To further investigate the role of neuronal CD200 on synaptic function, we depressed CD200 expression in neuron by hippocampal AAV injection and also evaluated microglial activation and cognitive and synaptic function. Interestingly, data revealed that neuronal CD200 deficiency significantly impairs synaptic and cognitive function. Taken these results together, we concluded that neuronal CD200 mediated microglial response and synaptic function during AD pathological development, and provided evidence that neuronal CD200 restoration ameliorates synaptic and cognitive deficits.