title: Beyond the monoaminergic hypothesis: neuroplasticity and epigenetic changes in a transgenic mouse model of depression.
abstract: The monoamine hypothesis of depression has dominated our understanding of both the pathophysiology of depression and the action of pharmacological treatments for the last decades, and it has led to the production of several generations of antidepressant agents. However, there are serious limitations to the current monoamine theory, and additional mechanisms, including hypothalamic-pituitary-adrenal (HPA) axis dysfunctions, as well as neurodegenerative and inflammatory alterations, are potentially associated with the pathogenesis of mood disorders. Moreover, new data have recently indicated that epigenetic mechanisms such as histone modifications and DNA methylation could affect diverse pathways leading to depression-like behaviours in animal models. In a transgenic mouse model of depression, in which a downregulation of glucocorticoid receptors (GR) causes a deficit in the HPA axis feedback control, besides alterations in monoamine neurotransmission and neuroplasticity, we found modifications in the expression of many proteins involved in epigenetic regulation, as well as clock genes, in the hippocampus and the frontal cortex, that might be central in the genesis of depressive-like behaviours.
authors: Inserm, U894, , Centre de Psychiatrie et Neurosciences, 75013 Paris,  France.
authors: Renaud
authors: R
authors: Massart
authors: Raymond
authors: R
authors: Mongeau
authors: Laurence
authors: L
authors: Lanfumey
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D018377:Neurotransmitter Agents / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D000928:Antidepressive Agents; D018377:Neurotransmitter Agents; D011965:Receptors, Glucocorticoid; D012701:Serotonin; D056926:CLOCK Proteins; C538944:Clock protein, mouse