title: Hippocampal neurogenesis response: What can we expect from two different models of hypertension?
abstract: Hypertension is associated with cerebrovascular disease, white matter lesion and cognitive deficit, both in experimental models and clinical observations. Furthermore, in non-clinical models it is shown that hippocampus is affected by hypertension and hypoxia. Herein, two distinct hypertension models were used to study neurogenic response in hippocampus. Dahl salt sensitive (DSS) rat model is a genetic based idiopathic model, while chronic intermittent hypoxia (CIH) mimics the hypertension observed in patients with obstructive sleep apnea (OSA). Both models are chronic and trigger hypertension. No macroscopic alterations based on histological analysis were found in hippocampus derived from DSS and CIH exposure rats. Nevertheless, in hippocampus derived from CIH-induced hypertensive rats, there was a decrease on neuronal population (MAP2 and NeuN positive cells) and an increase on astrocytic marker GFAP. Accordingly, a higher increase on Ki67 expressing cells was found in dentate gyrus (DG) region, suggesting an enhancement of cell proliferation, concomitantly with an increase of Nestin staining, which indicates the presence of immature neurons under differentiation. While, in hippocampus of DSS rats with or without high salt diet, there was no remarkable difference indicating potential neuronal loss, astrocytic activation or neurogenesis. Furthermore, in both models hypertension did not alter the levels of expression of the stress response enzyme heme oxygenase-1 in DG. These data indicate that intermittent hypoxia might be the key factor involved in neurogenesis modulation in hippocampus. Furthermore, two hypotheses can be explored: (i) activation of neurogenesis is a response against neuronal loss induced by hypertension and/or hypoxia or (ii) neurogenesis can be directly stimulated by hypoxia as a neuroprotective mechanism.
authors.affiliation: CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pedroso
authors.affiliation: CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Nunes
authors.affiliation: CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal.
authors.forename: Lucília N
authors.initials: LN
authors.lastname: Diogo
authors.affiliation: INSERM UMR-S 1180-LabEx LERMIT, Université Paris-Sud, 5 rue Jean-Baptiste Clément, 92296 Châtenay Malabry, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Oudot
authors.affiliation: CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal.
authors.forename: Emília C
authors.initials: EC
authors.lastname: Monteiro
authors.affiliation: INSERM UMR-S 1180-LabEx LERMIT, Université Paris-Sud, 5 rue Jean-Baptiste Clément, 92296 Châtenay Malabry, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Brenner
authors.affiliation: CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal; Instituto de Biologia Experimental e Tecnológica (iBET), Apartado 12, 2781-901 Oeiras, Portugal.
authors.forename: Helena L A
authors.initials: HLA
authors.lastname: Vieira
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001794:Blood Pressure; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006339:Heart Rate; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D017208:Rats, Wistar
chemical_list: D008565:Membrane Proteins; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Cell proliferation; Dahl rat; Hippocampus; Hypertension; IntermIttent hypoxia; NeurogeNesis