title: Chronic fluoxetine treatment increases the expression of PSA-NCAM in the medial prefrontal cortex.
abstract: Recent hypotheses suggest that changes in neuronal structure and connectivity may underlie the etiology of depression. The medial prefrontal cortex (mPFC) is affected by depression and shows neuronal remodeling during adulthood. This plasticity may be mediated by the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), which is intensely expressed in the adult mPFC. As the expression of PSA-NCAM is increased by serotonin in other cerebral regions, antidepressants acting on serotonin reuptake may influence PSA-NCAM expression and thus counteract the effects of depression by modulating neuronal structural plasticity. Using immunohistochemistry, we have studied the relationship between serotoninergic fibers and PSA-NCAM expressing neurons in the adult rat mPFC and the expression of serotonin receptors in these cells. The effects of fluoxetine treatment for 14 days on mPFC PSA-NCAM expression have also been analyzed. Although serotoninergic fibers usually do not contact PSA-NCAM immunoreactive neurons, most of these cells express 5-HT3 receptors. In general, chronic fluoxetine treatment induces significant increases in the number of PSA-NCAM immunoreactive neurons and in neuropil immunostaining and coadministration of the 5-HT3 antagonist ondansetron blocks the effects of fluoxetine on PSA-NCAM expression. These results indicate that fluoxetine, acting through 5-HT3 receptors, can modulate PSA-NCAM expression in the mPFC. This modulation may mediate the structural plasticity of this cortical region and opens new perspectives on the study of the molecular bases of depression.
authors.affiliation: Cell Biology Department, Neurobiology Unit, Program in Basic and Applied Neurosciences, Universitat de València, Burjassot, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Varea
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Blasco-Ibáñez
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Gómez-Climent
authors.forename: Esther
authors.initials: E
authors.lastname: Castillo-Gómez
authors.forename: Carlos
authors.initials: C
authors.lastname: Crespo
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Martínez-Guijarro
authors.forename: Juan
authors.initials: J
authors.lastname: Nácher
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage*; D002452:Cell Count / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D005473:Fluoxetine / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D039842:Neural Cell Adhesion Molecule L1; D011985:Receptors, Serotonin; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D005473:Fluoxetine