Exploring the effects of collapsin response mediator protein 5 (CRMP5) on social deficits and memory impairment in a mouse model of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by several behavioral disturbances especially cognitive decline In addition to cognitive decline AD also exhibits several psychiatric symptoms such as delusion emotional changes and apathy Remarkably apathy in AD is characterized by lacking motivation loss of interesting and social problems It is worth noting that decreased social activity would accelerate AD progression whereas enhanced social interactions could rescue AD-induced memory impairment Thus social impairment may be a key factor in explaining the etiology of AD Collapsin response mediator protein 5 (CRMP5) one of the CRMP members expresses abundantly in the brain and is involved in the mental disorders and neurodegenerative diseases Previous studies suggest that CRMP5 is involved in neurite outgrowth and dendrite development in the hippocampus which is a pivotal brain area for regulating memory emotional and behavioral presentation However the specific functions of CRMP5 in AD are still unclear Thus this study aimed to explore the roles of CRMP5 in the social behaviors and memory performances of the 3xTg-AD mouse model Here we showed that 9-month-old 3xTg-AD mice exhibited social behavioral deficits and higher hippocampal CRMP5 levels than 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 CRMP5 rescued AD-induced memory impairment but overexpression of CRMP5 accelerated memory loss only in 3xTg-AD mice Moreover we also found that surface GluA2 levels were affected by manipulations of CRMP5 expressions These results demonstrated that CRMP5 expressions could regulate the social behaviors via modulation of the surface GluA2 trafficking and affected the memory performances in 3xTg-AD mice

Date of Award	2019
Original language	English
Supervisor	Ya-Hsin Hsiao (Supervisor)