Article

Enhanced Long-Term Synaptic Depression in an Animal Model of Depression

Department of Psychiatry, University of Freiburg, Freiburg, Germany.
Biological Psychiatry (Impact Factor: 10.26). 08/2007; 62(1):92-100. DOI: 10.1016/j.biopsych.2006.07.007
Source: PubMed

ABSTRACT

A growing body of evidence suggests a disturbance of brain plasticity in major depression. In contrast to hippocampal neurogenesis, much less is known about the role of synaptic plasticity. Long-term potentiation (LTP) and long-term depression (LTD) regulate the strength of synaptic transmission and the formation of new synapses in many neural networks. Therefore, we examined the modulation of synaptic plasticity in the chronic mild stress animal model of depression.
Adult rats were exposed to mild and unpredictable stressors for 3 weeks. Thereafter, long-term synaptic plasticity was examined in the hippocampal CA1 region by whole-cell patch clamp measurements in brain slices. Neurogenesis was assessed by doublecortin immunostaining.
Exposure to chronic mild stress facilitated LTD and had no effect on LTP. Chronic application of the antidepressant fluvoxamine during the stress protocol prevented the facilitation of LTD and increased the extent of LTP induction. Neurogenesis in the dentate gyrus was impaired after chronic stress.
In addition to neurogenesis, long-term synaptic plasticity is an important and ubiquitous form of brain plasticity that is disturbed in an animal model of depression. Facilitated depression of synaptic transmission might impair function and structure of brain circuits involved in the pathophysiology of major depression. Antidepressants might counteract these alterations.

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Available from: Claus Normann, Jul 15, 2015
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    • "Moreover, chronic stress decreases the number and function of AMPA receptors in the hippocampus, which relates to disrupted memory consolidation and anhedonic behavior in rats[19]. In turn, chronic application of the antidepressant fluvoxamine during stress protocols prevents the facilitation of LTD and increases the extent of LTP induction[17]. In humans, some studies have begun to provide evidence for an impairment of synaptic plasticity in MDD using non-invasive, indirect indices of LTP. "
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    • "In contrast, chronic mild stress in animals facilitates the induction of synaptic long-term depression (LTD) that decreases synaptic transmission (Holderbach et al, 2007; Xu et al, 1997). Diverse antidepressant treatments reverse these effects (Holderbach et al, 2007; Rocher et al, 2004). Some studies have begun to translate this concept assessing non-invasive indices of synaptic plasticity in humans. "
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    • "In animals, chronic stress severely disturbs synaptic plasticity. For example, changes in the strength or efficacy of synaptic transmission result in hippocampal structural and functional incoordination (Sousa et al., 2000; Kim et al., 2006; Holderbach et al., 2007; Pittenger and Duman, 2008). In humans, the sustained increase of hippocampal excitatory synaptic transmission following stress may underlie the dendritic remodeling and volumetric shrinkage associated with stressrelated pathologies (Maras and Baram, 2012; Sanacora et al., 2012). "

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