title: Effects of long-term adrenalectomy on apoptosis and neuroprotection in the rat hippocampus.
abstract: Reduction in corticosterone by acute adrenalectomy (5 d) promotes apoptosis in dentate gyrus (DG) granular neurons, an effect concomitant with variations in the expression of the Bcl-2 gene family implicated in apoptotic regulation. However, no studies exist correlating the effect of long-term adrenalectomy (30 d) on the hippocampus in terms of extent of apoptosis and the levels of proteins related to an apoptotic cascade. After 5 d of adrenalectomy, we found an increase in apoptosis of the DG granular region, correlated with an increase in the processing of caspase-9. The magnitude of apoptosis 30 d after adrenalectomy was reduced in the DG granular layer compared with 5 d after adrenalectomy, in close relation to a reduction in the level of processed caspase-9. To understand how the increase in cell survival long after adrenalectomy occurs, we analyzed changes in the expression of genes and proteins related to apoptosis. Long-term adrenalectomy did not change hippocampal pro-apoptotic Bax or antiapoptotic Bcl-2 mRNA levels or protein content with respect to control. However, we found an increase in mRNA levels of the GD's Bcl-x gene, in parallel with the increase in anti-apoptotic BCL-XL protein levels. These results suggest the reduction in apoptosis observed after long-term adrenalectomy occurs through mechanisms that repress proapoptotic genes previously found to be increased at shorter times of adrenalectomy.
authors.affiliation: Laboratory of Neurobiochemistry, Department of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, Universidad de Chile, P.O. Box 233, Santiago 1, Chile.
authors.forename: Sergio
authors.initials: S
authors.lastname: Andrés
authors.forename: Sergio
authors.initials: S
authors.lastname: Cárdenas
authors.forename: Claudio
authors.initials: C
authors.lastname: Parra
authors.forename: Javier
authors.initials: J
authors.lastname: Bravo
authors.forename: Monika
authors.initials: M
authors.lastname: Greiner
authors.forename: Paulina
authors.initials: P
authors.lastname: Rojas
authors.forename: Paola
authors.initials: P
authors.lastname: Morales
authors.forename: Hernán
authors.initials: H
authors.lastname: Lara
authors.forename: Jenny
authors.initials: J
authors.lastname: Fiedler
mesh_terms: D000315:Adrenalectomy / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D008297:Male; D008954:Models, Biological; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C506435:Casp9 protein, rat; D053453:Caspase 9; D020169:Caspases