title: Sex-Specific and Estrous Cycle-Dependent Antidepressant-Like Effects and Hippocampal Akt Signaling of Leptin.
abstract: Sex differences in the incidence of depression and antidepressant treatment responses are well documented. Depression is twice as common in women as in men. Recent studies indicate that low levels of leptin, an adipocyte-derived hormone, are associated with increased symptoms of depression in women. Leptin has been shown to produce antidepressant-like effects in male rodents. In the present study, we examined sex differences and estrous cycle variations in antidepressant-like responses to leptin. Leptin administration significantly reduced immobility, a putative measure of behavioral despair, in the forced swim test in intact female mice in the proestrus phase but not in the diestrus phase of the estrous cycle. Moreover, leptin administration stimulated Akt phosphorylation in the hippocampus of female mice in proestrus but not in diestrus, in correlation with its differential behavioral effects in these two phases of the cycle. Leptin-induced behavioral responses and stimulation of hippocampal Akt phosphorylation in female mice were abolished by ovariectomy. By contrast, the antidepressant-like effect of leptin in male mice was not affected by gonadectomy (castration). Pretreatment with 17β-estradiol restored sensitivity to the effects of leptin on behavior and hippocampal Akt phosphorylation in ovariectomized female mice. These results suggest leptin regulates depression-like behavior and hippocampal Akt signaling in a sex-specific and estrous cycle-dependent manner.
authors.affiliation: Department of Pharmacology (N.C., X.W., L.S., X.-Y.L.), The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute for Metabolic and Neuropsychiatric Disorders (X.W., L.S.), Binzhou Medical University, Yantai 256603, China.
authors.forename: Nicole
authors.initials: N
authors.lastname: Carrier
authors.affiliation: Department of Pharmacology (N.C., X.W., L.S., X.-Y.L.), The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute for Metabolic and Neuropsychiatric Disorders (X.W., L.S.), Binzhou Medical University, Yantai 256603, China.
authors.forename: Xuezhen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology (N.C., X.W., L.S., X.-Y.L.), The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute for Metabolic and Neuropsychiatric Disorders (X.W., L.S.), Binzhou Medical University, Yantai 256603, China.
authors.forename: Linshan
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Pharmacology (N.C., X.W., L.S., X.-Y.L.), The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute for Metabolic and Neuropsychiatric Disorders (X.W., L.S.), Binzhou Medical University, Yantai 256603, China.
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Lu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D015153:Blotting, Western; D002369:Castration; D004031:Diestrus / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D030762:Estrous Cycle / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010052:Ovariectomy; D010766:Phosphorylation / Q000187:drug effects; D011359:Proestrus / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects*; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D004967:Estrogens; D020738:Leptin; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt