title: The expression of plasticity-related genes in an acute model of stress is modulated by chronic desipramine in a time-dependent manner within medial prefrontal cortex.
abstract: It is well established that stress plays a major role in the pathogenesis of neuropsychiatric diseases. Stress-induced alteration of synaptic plasticity has been hypothesized to underlie the morphological changes observed by neuroimaging in psychiatric patients in key regions such as hippocampus and prefrontal cortex (PFC). We have recently shown that a single acute stress exposure produces significant short-term alterations of structural plasticity within medial PFC. These alterations were partially prevented by previous treatment with chronic desipramine (DMI). In the present study we evaluated the effects of acute Foot-shock (FS)-stress and pre-treatment with the traditional antidepressant DMI on the gene expression of key regulators of synaptic plasticity and structure. Expression of Homer, Shank, Spinophilin, Densin-180, and the small RhoGTPase related gene Rac1 and downstream target genes, Limk1, Cofilin1 and Rock1 were investigated 1 day (1d), 7 d and 14d after FS-stress exposure. We found that DMI specifically increases the short-term expression of Spinophilin, as well as Homer and Shank family genes, and that both acute stress and DMI exert significant long-term effects on mRNA levels of genes involved in spine plasticity. These findings support the knowledge that acute FS stress and antidepressant treatment induce both rapid and sustained time-dependent alterations in structural components of synaptic plasticity in rodent medial PFC.
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark; Translational Neuropsychiatry Unit, Aarhus University Hospital, Risskov, Denmark. Electronic address: nava.nicoletta@gmail.com.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Nava
authors.affiliation: Translational Neuropsychiatry Unit, Aarhus University Hospital, Risskov, Denmark; Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita´ di Milano, Milano, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Treccani
authors.affiliation: Translational Neuropsychiatry Unit, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Heidi Kaastrup
authors.initials: HK
authors.lastname: Müller
authors.affiliation: Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita´ di Milano, Milano, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
authors.affiliation: Translational Neuropsychiatry Unit, Aarhus University Hospital, Risskov, Denmark; Pharmaceutical Research Centre of Excellence, School of Pharmacy, North-West University, Potchefstroom, South Africa.
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
authors.affiliation: Translational Neuropsychiatry Unit, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Betina
authors.initials: B
authors.lastname: Elfving
mesh_terms: D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003345:Corticosterone / Q000378:metabolism; D003891:Desipramine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D000099273:Neurabins
chemical_list: D051339:Actin Depolymerizing Factors; D000929:Antidepressive Agents, Tricyclic; D003345:Corticosterone; D003891:Desipramine; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D012795:Sialoglycoproteins; D020830:rac1 GTP-Binding Protein; D000099273:Neurabins; C504463:Lrrc7 protein, rat
keywords: Acute stress; Antidepressant; Prefrontal cortex; Real-time qPCR; Synaptic plasticity