Imbalance of synaptic and extrasynaptic NMDA receptors induced by the deletion of CRMP1 accelerates age-related cognitive decline in mice
Journal
Neurobiology of aging
Journal Volume
135
Date Issued
2024-03
Author(s)
Tsai, Yun-Chieh
Huang, Sheng-Min
Peng, Hsu-Hsia
Lin, Shu-Rung
Chin, Ting-Yu
Huang, Shih-Ming
Abstract
Collapsin response mediator protein 1 (CRMP1) is involved in semaphorin 3A signaling pathway, promoting neurite extension and growth cone collapse. It is highly expressed in the nervous system, especially the hippocampus. The crmp1 knockout (KO) mice display impaired spatial learning and memory, and this phenomenon seemingly tends to deteriorate with age. Here we investigated whether CRMP1 is involved in age-related cognitive decline in WT and crmp1 KO mice at adult, middle-aged and older stages. The results revealed that cognitive dysfunction in the Morris water maze task became more severe and decreased glutamate and glutamine level in middle-aged crmp1 KO mice. Additionally, increasing levels of extrasynaptic NMDA receptors and phosphorylation of Tau were observed in middle-aged crmp1 KO mice, leading to synaptic and neuronal loss in the CA3 regions of hippocampus. These findings suggest that deletion of CRMP1 accelerates age-related cognitive decline by disrupting the balance between synaptic and extrasynaptic NMDA receptors, resulting in the loss of synapses and neurons.
Subjects
Age-related cognitive decline; CRMP1; Extrasynaptic NMDA receptor; Phosphorylated Tau; Synaptic NMDA receptor
SDGs
Type
journal article