Memory Decline and Aberration of Synaptic Proteins in X-Linked Moesin Knockout Male Mice

• 발행기관: 대한신경정신의학회
• 저자명: Hua Cai Seong Mi Lee Yura Choi Bomlee Lee Soo Jung Im Dong Hyeon Kim Hyung Jun Choi Jin Hee Kim Yeni Kim Boo Ahn Shin Songhee Jeon
• 간행물 정보: 『Psychiatry Investigation』제22권 제1호, 10~25쪽, 전체 16쪽
• 주제분류: 의약학 > 정신과학
• 파일형태: PDF
• 발행일자: 2025.01.01

국문 초록

Objective: This study aims to investigate may moesin deficiency resulted in neurodevelopmental abnormalities caused by negative impact on synaptic signaling ultimately leading to synaptic structure and plasticity. Methods: Behavioral assessments measured neurodevelopment (surface righting, negative geotaxis, cliff avoidance), anxiety (open field test, elevated plus maze test), and memory (passive avoidance test, Y-maze test) in moesin-knockout mice (KO) compared to wild-type mice (WT). Whole exome sequencing (WES) of brain (KO vs. WT) and analysis of synaptic proteins were performed to determine the disruption of signal pathways downstream of moesin. Risperidone, a therapeutic agent, was utilized to reverse the neurodevelopmental aberrance in moesin KO. Results: Moesin-KO pups exhibited decrease in the surface righting ability on postnatal day 7 (p<0.05) and increase in time spent in the closed arms (p<0.01), showing increased anxiety-like behavior. WES revealed mutations in pathway aberration in neuron projection, actin filament-based processes, and neuronal migration in KO. Decreased cell viability (p<0.001) and expression of soluble NSF adapter protein 25 (SNAP25) (p<0.001) and postsynaptic density protein 95 (PSD95) (p<0.01) was observed in days in vitro 7 neurons. Downregulation of synaptic proteins, and altered phosphorylation levels of Synapsin I, mammalian uncoordinated 18 (MUNC18), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) was observed in KO cortex and hippocampus. Risperidone reversed the memory impairment in the passive avoidance test and the spontaneous alternation percentage in the Y maze test. Risperidone also restored the reduced expression of PSD95 (p<0.01) and the phosphorylation of Synapsin at Ser605 (p<0.05) and Ser549 (p<0.001) in the cortex of moesin-KO. Conclusion: Moesin deficiency leads to neurodevelopmental delay and memory decline, which may be caused through altered regulation in synaptic proteins and function.

목차

INTRODUCTION

METHODS

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키워드

Neurodevelopment Memory Moesin PSD95 Synapsin Risperidone