title: Dehydroepiandrosterone increases the number and dendrite maturation of doublecortin cells in the dentate gyrus of middle age male Wistar rats exposed to chronic mild stress.
abstract: Aging increases the vulnerability to stress and risk of developing depression. These changes have been related to a reduction of dehydroepiandrosterone (DHEA) levels, an adrenal steroid with anti-stress effects. Also, adult hippocampal neurogenesis decreases during aging and its alteration or impaired is related to the development of depression. Besides, it has been hypothesized that DHEA increases the formation of new neurons. However, it is unknown whether treatment with DHEA in aging may stimulate the dendrite maturation of newborn neurons and reversing depressive-like signs evoked by chronic stress exposure. Here aged male rats (14 months old) were subjected to a scheme of chronic mild stress (CMS) during six weeks, received a treatment with DHEA from the third week of CMS. Changes in body weight and sucrose preference (SP) were measured once a week. DHEA levels were measured in serum, identification of doublecortin-(DCX)-, BrdU- and BrdU/NeuN-labeled cells was done in the dentate gyrus of the hippocampus. CMS produced a gradual reduction in the body weight, but no changes in the SP were observed. Treatment enhanced levels of DHEA, but lack of recovery on body weight of stressed rats. Aging reduced the number of DCX-, BrdU- and BrdU/NeuN- cells but DHEA just significantly increased the number of DCX-cells in rats under CMS and controls, reaching levels of young non-stressed rats (used here as a reference of an optimal status of health). In rats under CMS, DHEA facilitated dendritic maturation of immature new neurons. Our results reveal that DHEA improves neural plasticity even in conditions of CMS in middle age rats. Thus, this hormone reverted the decrement of DCX-cells caused during normal aging.
authors.affiliation: Farmacología Conductual, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, C.P. 14370, México City, Mexico.
authors.forename: J J
authors.initials: JJ
authors.lastname: Herrera-Pérez
authors.affiliation: Farmacología Conductual, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, C.P. 14370, México City, Mexico. Electronic address: lucia@imp.edu.mx.
authors.forename: L
authors.initials: L
authors.lastname: Martínez-Mota
authors.affiliation: Farmacología Conductual, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, C.P. 14370, México City, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Jiménez-Rubio
authors.affiliation: Laboratorio de Neurogenesis, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, C.P. 14370, México City, Mexico.
authors.forename: L
authors.initials: L
authors.lastname: Ortiz-López
authors.affiliation: Laboratorio de Neurogenesis, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, C.P. 14370, México City, Mexico.
authors.forename: E A
authors.initials: EA
authors.lastname: Cabrera-Muñoz
authors.affiliation: Departamento de Infectología e Inmunología, Instituto Nacional de Perinatología, Montes Urales 800, Colonia Lomas de Virreyes, C.P. 11000, México City, Mexico.
authors.forename: N
authors.initials: N
authors.lastname: Galindo-Sevilla
authors.affiliation: Departamento de Nutrición Animal, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Avenida Vasco de Quiroga No. 15, Col. Belisario Domínguez Sección XVI, Tlalpan, C.P. 14080, México City, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Zambrano
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Coyoacán, Cd. Universitaria, C.P. 04510, México City, Mexico.
authors.forename: F
authors.initials: F
authors.lastname: Hernández-Luis
authors.affiliation: Laboratorio de Neurogenesis, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, C.P. 14370, México City, Mexico. Electronic address: gbernabe@imp.edu.mx.
authors.forename: G B
authors.initials: GB
authors.lastname: Ramírez-Rodríguez
authors.affiliation: Catedrática del Consejo Nacional de Ciencia y Tecnología, Av. Insurgentes Sur 1582, Col. Crédito Constructor, Del. Benito Juárez, C.P. 03940, México City, Mexico; Clínica de Trastornos Afectivos, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz". Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, C.P. 14370, México City, Mexico. Electronic address: monica.flores@imp.edu.mx.
authors.forename: M
authors.initials: M
authors.lastname: Flores-Ramos
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D003687:Dehydroepiandrosterone / Q000097:blood / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019422:Dietary Sucrose; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D011619:Psychotropic Drugs / Q000097:blood / Q000494:pharmacology*; D011897:Random Allocation; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D034961:Antigens, Nuclear; C000714848:Dcx protein, rat; D019422:Dietary Sucrose; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011619:Psychotropic Drugs; C546339:Rbfox3 protein, rat; D003687:Dehydroepiandrosterone; D001973:Bromodeoxyuridine
keywords: Adult neurogenesis; Aging; Chronic mild stress; Dehydroepiandrosterone; Doublecortin; Middle age