Hippocampus- and neocortex-specific deletion of Aeg-1 causes learning memory impairment and depression in mice

Astrocyte elevated gene-1 (AEG-1) has been characterized as an oncogene promoting the progression of various tumors. The role of AEG-1 in neurological diseases was highlighted by recent researches. However, the physiological function of AEG-1 remains elusive. Our study aimed to investigate the physiological role of AEG-1 in the central nervous system by generating a mouse model with specific deletion of Aeg-1 in the hippocampus and neocortex (Aeg-1^fl/flCre⁺ mice). Behavioral assessments revealed that Aeg-1 deficiency caused impaired learning and memory capabilities in juvenile and adult mice. Depressive-like behaviors were also observed in Aeg-1^fl/flCre⁺ mice. Gene Ontology (GO) enrichment analyses indicated that AEG-1 was involved in the neuronal morphogenesis. Interestingly, Aeg-1 knockout was irrelevant to the neuron loss but reduced the dendritic length and the dendritic spines density in hippocampus. Electrophysiological analyses showed a decreased response of paired-pulse facilitation (PPF) and a compromised efficiency of excitatory synaptic transmission following Aeg-1 deletion in hippocampus. In conclusion, our findings suggest that Aeg-1 deficiency in the hippocampus and neocortex leads to learning and memory impairments and depression in mice, which is mediated by the abnormalities of neuronal morphology and the impaired synaptic functions.