Early life stress differentially modulates distinct forms of brain plasticity in young and adult mice.
BACKGROUND
Early life trauma is an important risk factor for many psychiatric and somatic disorders in adulthood. As a growing body of evidence suggests that brain plasticity is disturbed in affective disorders, we examined the short-term and remote effects of early life stress on different forms of brain plasticity.


RESULTS
Mice were subjected to early deprivation by individually separating pups from their dam in the first two weeks after birth. Distinct forms of brain plasticity were assessed in the hippocampus by longitudinal MR volumetry, immunohistochemistry of neurogenesis, and whole-cell patch-clamp measurements of synaptic plasticity. Depression-related behavior was assessed by the forced swimming test in adult animals. Neuropeptides and their receptors were determined by real-time PCR and immunoassay. Early maternal deprivation caused a loss of hippocampal volume, which returned to normal in adulthood. Adult neurogenesis was unaffected by early life stress. Long-term synaptic potentiation, however, was normal immediately after the end of the stress protocol but was impaired in adult animals. In the forced swimming test, adult animals that had been subjected to early life stress showed increased immobility time. Levels of substance P were increased both in young and adult animals after early deprivation.


CONCLUSIONS
Hippocampal volume was affected by early life stress but recovered in adulthood which corresponded to normal adult neurogenesis. Synaptic plasticity, however, exhibited a delayed impairment. The modulation of synaptic plasticity by early life stress might contribute to affective dysfunction in adulthood.
Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Freiburg, Germany.
Inga
I
Herpfer
Henning
H
Hezel
Wilfried
W
Reichardt
Kristin
K
Clark
Julia
J
Geiger
Claus M
CM
Gross
Andrea
A
Heyer
Valentin
V
Neagu
Harsharan
H
Bhatia
Hasan C
HC
Atas
Bernd L
BL
Fiebich
Josef
J
Bischofberger
Carola A
CA
Haas
Klaus
K
Lieb
Claus
C
Normann
D000818:Animals; D001522:Behavior, Animal; D015536:Down-Regulation; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D046353:Immobility Response, Tonic; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis; D009473:Neuronal Plasticity / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D013315:Stress, Psychological / Q000503:physiopathology*; D013373:Substance P / Q000378:metabolism; D013550:Swimming
D009479:Neuropeptides; D013373:Substance P