Remodeling of Hippocampal Spine Synapses in the Rat Learned Helplessness Model of Depression

T. Hajszán, Antonia Dow, Jennifer L. Warner-Schmidt, Klara Szigeti-Buck, Nermin L. Sallam, A. Párducz, Csaba Leranth, Ronald S. Duman

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Background: Although it has been postulated for many years that depression is associated with loss of synapses, primarily in the hippocampus, and that antidepressants facilitate synapse growth, we still lack ultrastructural evidence that changes in depressive behavior are indeed correlated with structural synaptic modifications. Methods: We analyzed hippocampal spine synapses of male rats (n = 127) with electron microscopic stereology in association with performance in the learned helplessness paradigm. Results: Inescapable footshock (IES) caused an acute and persistent loss of spine synapses in each of CA1, CA3, and dentate gyrus, which was associated with a severe escape deficit in learned helplessness. On the other hand, IES elicited no significant synaptic alterations in motor cortex. A single injection of corticosterone reproduced both the hippocampal synaptic changes and the behavioral responses induced by IES. Treatment of IES-exposed animals for 6 days with desipramine reversed both the hippocampal spine synapse loss and the escape deficit in learned helplessness. We noted, however, that desipramine failed to restore the number of CA1 spine synapses to nonstressed levels, which was associated with a minor escape deficit compared with nonstressed control rats. Shorter, 1-day or 3-day desipramine treatments, however, had neither synaptic nor behavioral effects. Conclusions: These results indicate that changes in depressive behavior are associated with remarkable remodeling of hippocampal spine synapses at the ultrastructural level. Because spine synapse loss contributes to hippocampal dysfunction, this cellular mechanism may be an important component in the neurobiology of stress-related disorders such as depression.

Original languageEnglish
Pages (from-to)392-400
Number of pages9
JournalBiological Psychiatry
Volume65
Issue number5
DOIs
Publication statusPublished - Mar 1 2009

Fingerprint

Learned Helplessness
Synapses
Spine
Depression
Desipramine
Neurobiology
Dentate Gyrus
Motor Cortex
Corticosterone
Antidepressive Agents
Hippocampus
Electrons
Injections

Keywords

  • Corticosterone
  • depression
  • desipramine
  • electron microscopic stereology
  • stress
  • synaptic plasticity

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Remodeling of Hippocampal Spine Synapses in the Rat Learned Helplessness Model of Depression. / Hajszán, T.; Dow, Antonia; Warner-Schmidt, Jennifer L.; Szigeti-Buck, Klara; Sallam, Nermin L.; Párducz, A.; Leranth, Csaba; Duman, Ronald S.

In: Biological Psychiatry, Vol. 65, No. 5, 01.03.2009, p. 392-400.

Research output: Contribution to journalArticle

Hajszán, T, Dow, A, Warner-Schmidt, JL, Szigeti-Buck, K, Sallam, NL, Párducz, A, Leranth, C & Duman, RS 2009, 'Remodeling of Hippocampal Spine Synapses in the Rat Learned Helplessness Model of Depression', Biological Psychiatry, vol. 65, no. 5, pp. 392-400. https://doi.org/10.1016/j.biopsych.2008.09.031
Hajszán, T. ; Dow, Antonia ; Warner-Schmidt, Jennifer L. ; Szigeti-Buck, Klara ; Sallam, Nermin L. ; Párducz, A. ; Leranth, Csaba ; Duman, Ronald S. / Remodeling of Hippocampal Spine Synapses in the Rat Learned Helplessness Model of Depression. In: Biological Psychiatry. 2009 ; Vol. 65, No. 5. pp. 392-400.
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