摘要
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.
| 原文 | English |
|---|---|
| 文章編號 | 107673 |
| 期刊 | Neuropharmacology |
| 卷 | 157 |
| DOIs | |
| 出版狀態 | Published - 2019 十月 1 |
指紋
All Science Journal Classification (ASJC) codes
- Pharmacology
- Cellular and Molecular Neuroscience
引用此文
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Collapsin response mediator protein 5 (CRMP5) causes social deficits and accelerates memory loss in an animal model of Alzheimer's disease. / Lin, Yung Shuen; Lin, Yu Fen; Chen, Kao-Ching; Yang, Yen-Kuang; Hsiao, Ya-Hsin.
於: Neuropharmacology, 卷 157, 107673, 01.10.2019.研究成果: Article
TY - JOUR
T1 - Collapsin response mediator protein 5 (CRMP5) causes social deficits and accelerates memory loss in an animal model of Alzheimer's disease
AU - Lin, Yung Shuen
AU - Lin, Yu Fen
AU - Chen, Kao-Ching
AU - Yang, Yen-Kuang
AU - Hsiao, Ya-Hsin
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuropharm.2019.107673
DO - 10.1016/j.neuropharm.2019.107673
M3 - Article
VL - 157
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
M1 - 107673
ER -