Chronic Social Stress Affects Synaptic Maturation of Newly Generated Neurons in the Adult Mouse Dentate Gyrus.
BACKGROUND
Chronic stress has been found to suppress adult neurogenesis, but it remains unclear whether it may affect the maturation process of adult-born neurons. Here, we examined the influence of chronic social defeat stress on the morphological and electrophysiological properties of adult-born dentate granule cells at different developmental stages.


METHODS
Adult C57BL/6 mice were subjected to 10 days of chronic social defeat stress followed by a social interaction test 24 hours after the last defeat. Defeated mice were segregated into susceptible and unsusceptible subpopulations based on a measure of social interaction test. Combining electrophysiology with retrovirus-mediated birth-dating and labeling, we examined the impact of chronic social defeat stress on temporal regulation of synaptic plasticity of adult-born dentate granule cells along their maturation.


RESULTS
Chronic social defeat stress decreases the survival and dendritic complexity of adult-born dentate granule cells. While chronic social defeat stress doesn't alter the intrinsic electrophysiological properties and synaptic transmission of surviving adult-born dentate granule cells, it promotes the developmental switch in synaptic N-methyl-D-aspartate receptors from predominant GluN2B- to GluN2A-containing receptors, which transform the immature synapse of adult-born dentate granule cells from one that exhibits enhanced long-term potentiation to one that has normal levels of long-term potentiation. Furthermore, chronic social defeat stress increases the level of endogenous repressor element-1 silencing transcription factor mRNA in adult-born dentate granule cells, and knockdown of the repressor element-1 silencing transcription factor in adult-born dentate granule cells rescues chronic social defeat stress-induced morphological deficits and accelerated developmental switch in synaptic N-methyl-D-aspartate receptor subunit composition.


CONCLUSIONS
These results uncover a previously unsuspected role of chronic social defeat stress in regulating adult neurogenesis and suggest that chronic social defeat stress can affect synaptic maturation process of adult-born dentate granule cells.
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Chien-Chung
CC
Chen
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Chiung-Chun
CC
Huang
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. richard@mail.ncku.edu.tw.
Kuei-Sen
KS
Hsu
D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D002908:Chronic Disease; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004291:Dominance-Subordination; D055785:Gene Knockdown Techniques; D007206:Individuality; D008297:Male; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012919:Social Behavior; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology*; D013569:Synapses / Q000473:pathology / Q000502:physiology*; D046509:Tissue Culture Techniques; D000099229:RE1-Silencing Transcription Factor
D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor
NMDA receptor; REST; adult neurogenesis; chronic social defeat stress; dentate granule cell