Hippocampal upregulation of the cyclooxygenase-2 gene following neonatal clomipramine treatment (a model of depression).
Although a putative role has been attributed to inflammation in the pathogenesis of depressive disorders, the relationship of prostaglandins, known mediators of inflammation, and depression has not been elucidated. Clomipramine is an antidepressive drug with a pro-depressive paradoxical effect in adult rats when administrated neonatally. Using this effect as a model of depression, we investigated the differential expression of the cyclooxygenase (COX-2) gene in rat brains. Rats injected neonatally with clomipramine showed depressive-like symptoms in adulthood, as well as decreased levels of the brain-derived neurotrophic factor (BDNF) and a quantitative differential expression of the COX-2 gene (Real Time PCR) and protein (immunohistochemistry) in the hippocampus. As evidenced, the relationship between a key enzyme in the prostaglandin synthesis and biological and behavioral depression-like changes opens an interesting line of investigation regarding the molecular bases of depression and its potential treatment through immunomodulatory drugs.
Unit of Brain Research, Instituto de Ciencias Básicas y Medicina Experimental del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. paola.cassano@hospitalitaliano.org.ar
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P
Cassano
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Hidalgo
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Burgos
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Adris
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Argibay
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002997:Clomipramine / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D003863:Depression / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000201:enzymology*; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; D051546:Cyclooxygenase 2; D002997:Clomipramine