Collapsin response mediator protein 5 (CRMP5) causes social deficits and accelerates memory loss in an animal model of Alzheimer's disease. (October 2019)

• Record Type: Journal Article
• Authors: Lin, Yung-Shuen; Lin, Yu-Fen; Chen, Kao Chin; Yang, Yen Kuang; Hsiao, Ya-Hsin
• Is Part Of: Neuropharmacology. Volume 157(2019)
• Publication Date: 2019-10
• Subjects: Alzheimer's disease -- social deficits -- Memory impairment -- 3xTg-AD mice -- CRMP5; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.107673
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by several behavioral disturbances, especially cognitive decline and deficits in social competence. Previous studies revealed that decreased social activity would accelerate AD progression, whereas enhanced social interaction could rescue AD-induced memory impairment. Collapsin response mediator protein 5 (CRMP5), which belongs to a family of cytosolic proteins, is abundantly expressed in the brain and is involved in the regulation of neurodevelopment and the pathology of several neuropsychiatric diseases. However, the functions of CRMP5 in AD are still unclear. Here, we demonstrated that 9-month-old 3xTg-AD mice exhibited social behavioral deficits and increased hippocampal CRMP5 levels compared to control (B6129S) mice. Knockdown of CRMP5 reversed the social deficits in 9-month-old 3xTg-AD mice, whereas CRMP5 overexpression decreased social interaction in both 3xTg-AD and control mice at 6 months of age. Interestingly, decreased expression of CRMP5 rescued AD-induced memory impairment, but overexpression of CRMP5 accelerated memory loss only in 3xTg-AD mice. In addition, we found that CRMP5 could regulate surface GluA2 and GluA2 S880 phosphorylation. These results suggest that CRMP5 regulates social behavior via modulation of surface GluA2 trafficking and affects memory performance in 3xTg-AD mice. Graphical abstract: Image 1 Highlights: CRMP5 is highly expressed in the hippocampi of 9-month-old 3xTg-AD mice. CRMP5 triggers social deficits in both B6129S and 3xTg-AD mice. Overexpression of CRMP5 exacerbated memory loss only in 3xTg-AD mice. CRMP5 could modulate GluA2 endocytosis via phosphorylated GluA2 S880.