CALHM2 V136G polymorphism reduces astrocytic ATP release and is associated with depressive symptoms and Alzheimer's disease risk.
Alzheimers Dement
; 19(10): 4407-4420, 2023 Oct.
Article
em En
| MEDLINE
| ID: mdl-37493186
ABSTRACT
INTRODUCTION:
Depression is considered a prodromal state of Alzheimer's disease (AD), yet the underlying mechanism(s) by which depression increases the risk of AD are not known.METHODS:
Single-nucleotide polymorphism (SNP) analysis was used to determine the CALHM2 variants in AD patients. Cellular and molecular experiments were conducted to investigate the function of CALHM2 V136G mutation. We generated a new genetically engineered Calhm2 V136G mouse model and performed behavioral tests with these mice.RESULTS:
CALHM2 V136G mutation (rs232660) is significantly associated with AD. V136G mutation resulted in loss of the CALHM2 ATP-release function in astrocytes and impaired synaptic plasticity. Mice homozygous for the Calhm2 V136G allele displayed depressive-like behaviors that were rescued by administration of exogenous ATP. Moreover, Calhm2 V136G mutation predisposed mice to cognitive decline in old age.DISCUSSION:
CALHM2 dysfunction is a biologically relevant mechanism that may contribute to the observed clinical correlation between depression and AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Alzheimers Dement
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China