Targeting Kruppel-like Factor 9 in Excitatory Neurons Protects against Chronic Stress-Induced Impairments in Dendritic Spines and Fear Responses.
Cell Rep
; 23(11): 3183-3196, 2018 06 12.
Article
em En
| MEDLINE
| ID: mdl-29898391
ABSTRACT
Stress exposure is associated with the pathogenesis of psychiatric disorders, including post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). Here, we show in rodents that chronic stress exposure rapidly and transiently elevates hippocampal expression of Kruppel-like factor 9 (Klf9). Inducible genetic silencing of Klf9 expression in excitatory forebrain neurons in adulthood prior to, but not after, onset of stressor prevented chronic restraint stress (CRS)-induced potentiation of contextual fear acquisition in female mice and chronic corticosterone (CORT) exposure-induced fear generalization in male mice. Klf9 silencing prevented chronic CORT and CRS induced enlargement of dendritic spines in the ventral hippocampus of male and female mice, respectively. KLF9 mRNA density was increased in the anterior dentate gyrus of women, but not men, with more severe recent stressful life events and increased mortality. Thus, Klf9 functions as a stress-responsive transcription factor that mediates circuit and behavioral resilience in a sex-specific manner.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Psicológico
/
Espinhas Dendríticas
/
Fatores de Transcrição Kruppel-Like
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article