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Chronic stress alters inhibitory networks in the medial prefrontal cortex of adult mice

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Abstract

Chronic stress in experimental animals induces dendritic atrophy and decreases spine density in principal neurons of the medial prefrontal cortex (mPFC). This structural plasticity may play a neuroprotective role and underlie stress-induced behavioral changes. Different evidences indicate that the prefrontocortical GABA system is also altered by stress and in major depression patients. In the amygdala, chronic stress induces dendritic remodeling both in principal neurons and in interneurons. However, it is not known whether similar structural changes occur in mPFC interneurons. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) may mediate these changes, because it is known to influence the dendritic organization of adult cortical interneurons. We have analyzed the dendritic arborization and spine density of mPFC interneurons in adult mice after 21 days of restraint stress and have found dendritic hypertrophy in a subpopulation of interneurons identified mainly as Martinotti cells. This aversive experience also decreases the number of glutamate decarboxylase enzyme, 67 kDa isoform (GAD67) expressing somata, without affecting different parameters related to apoptosis, but does not alter the number of interneurons expressing PSA-NCAM. Quantitative retrotranscription-polymerase chain reaction (qRT-PCR) analysis of genes related to general and inhibitory neurotransmission and of PSA synthesizing enzymes reveals increases in the expression of NCAM, synaptophysin and GABA(A)α1. Together these results show that mPFC inhibitory networks are affected by chronic stress and suggest that structural plasticity may be an important feature of stress-related psychiatric disorders where this cortical region, specially their GABAergic system, is altered.

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Acknowledgments

Spanish Ministry of Science and Innovation (MICINN-FEDER) BFU2009-12284/BFI, MICINN-PIM2010ERN-00577/NEUCONNECT in the frame of “ERA-NET NEURON”, Generalitat Valenciana ACOMP/2012/229 to JN. Javier Gilabert-Juan has a FPU predoctoral fellowship from the Spanish Ministry of Education and Science (AP2008-00937).

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Authors and Affiliations

  1. Program in Basic and Applied Neurosciences, Neurobiology Unit, Cell Biology Department, Universitat de València, Dr. Moliner 50, Burjassot, 46100, Valencia, Spain

    Javier Gilabert-Juan, Esther Castillo-Gomez, Ramón Guirado & Juan Nacher

  2. Genetics Department, Universitat de València, Valencia, Spain

    Javier Gilabert-Juan & Maria Dolores Moltó

  3. Fundación Investigación Hospital Clínico de Valencia, INCLIVA, Valencia, Spain

    Javier Gilabert-Juan, Maria Dolores Moltó & Juan Nacher

  4. CIBERSAM: Spanish National Network for Research in Mental Health, Madrid, Spain

    Javier Gilabert-Juan, Maria Dolores Moltó & Juan Nacher

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  1. Javier Gilabert-Juan
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  2. Esther Castillo-Gomez
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  4. Maria Dolores Moltó
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Correspondence to Juan Nacher.

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Gilabert-Juan, J., Castillo-Gomez, E., Guirado, R. et al. Chronic stress alters inhibitory networks in the medial prefrontal cortex of adult mice. Brain Struct Funct 218, 1591–1605 (2013). https://doi.org/10.1007/s00429-012-0479-1

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  • DOI: https://doi.org/10.1007/s00429-012-0479-1

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