Comorbidity between epilepsy and depression: experimental evidence for the involvement of serotonergic, glucocorticoid, and neuroinflammatory mechanisms.
Depression represents one of the most common comorbidities of temporal lobe epilepsy (TLE), and has profound negative impact on the quality of life of patients with TLE. However, causes and mechanisms of depression in TLE remain poorly understood, and effective therapies are lacking. We examined whether a commonly used model of TLE in rats could be used as a model of comorbidity between epilepsy and depression suitable for both mechanistic studies and for the development of mechanism-based antidepressant therapies. We established that animals that had been subjected to lithium chloride and pilocarpine status epilepticus (SE) and developed spontaneous recurrent seizures, exhibited a set of impairments congruent with a depressive state: behavioral equivalents of anhedonia and despair, dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, and compromised raphe-hippocampal serotonergic transmission. Pharmacologic studies have suggested that depressive impairments following SE develop as a result of enhanced interleukin-1beta signaling in the hippocampus, which leads to depression via inducing perturbations in the HPA axis and subsequent deficit in the raphe-hippocampal serotonergic transmission.
Pineda
Eduardo
E
Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1752, USA.
Shin
Don
D
Sankar
Raman
R
Mazarati
Andrey M
AM
D000818:Animals; D003292:Convulsants / Q000494:pharmacology; D003866:Depressive Disorder / Q000150:complications* / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000150:complications* / Q000209:etiology / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D053583:Interleukin-1beta / Q000502:physiology; D018021:Lithium Chloride / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D011903:Raphe Nuclei / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D003292:Convulsants; D053583:Interleukin-1beta; D011965:Receptors, Glucocorticoid; D010862:Pilocarpine; D012701:Serotonin; D018021:Lithium Chloride