title: Aging process alters hippocampal and cortical secretase activities of Wistar rats.
abstract: A growing body of evidence has demonstrated amyloid plaques in aged brain; however, little attention has been given to amyloid precursor protein (APP) processing machinery during the healthy aging process. The amyloidogenic and non-amyloidogenic pathways, represented respectively by β- and α-secretases (BACE and TACE), are responsible for APP cleavage. Our working hypothesis is that the normal aging process could imbalance amyloidogenic and non-amyloidogenic pathways specifically BACE and TACE activities. Besides, although it has been showed that exercise can modulate secretase activities in Alzheimer Disease models the relationship between exercise effects and APP processing during healthy aging process is rarely studied. Our aim was to investigate the aging process and the exercise effects on cortical and hippocampal BACE and TACE activities and aversive memory performance. Young adult and aged Wistar rats were subjected to an exercise protocol (20min/day for 2 weeks) and to inhibitory avoidance task. Biochemical parameters were evaluated 1h and 18h after the last exercise session in order to verify transitory and delayed exercise effects. Aged rats exhibited impaired aversive memory and diminished cortical TACE activity. Moreover, an imbalance between TACE and BACE activities in favor of BACE activity was observed in aged brain. Moderate treadmill exercise was unable to alter secretase activities in any brain areas or time points evaluated. Our results suggest that aging-related aversive memory decline is partly linked to decreased cortical TACE activity. Additionally, an imbalance between secretase activities can be related to the higher vulnerability to neurodegenerative diseases induced by aging.
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Karine
authors.initials: K
authors.lastname: Bertoldi
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Laura Reck
authors.initials: LR
authors.lastname: Cechinel
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Schallenberger
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Louisiana
authors.initials: L
authors.lastname: Meireles
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Basso
authors.affiliation: Faculdade de Fisioterapia, Universidade Federal de Santa Catarina, Araranguá, Santa Catarina, Brazil.
authors.forename: Gisele Agustini
authors.initials: GA
authors.lastname: Lovatel
authors.affiliation: Faculdade de Odontologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Lisiane
authors.initials: L
authors.lastname: Bernardi
authors.affiliation: Faculdade de Odontologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Marcelo Lazzaron
authors.initials: ML
authors.lastname: Lamers
authors.affiliation: Programa de Pós Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: ionara@ufrgs.br.
authors.forename: Ionara Rodrigues
authors.initials: IR
authors.lastname: Siqueira
mesh_terms: D000072198:ADAM17 Protein / Q000378:metabolism*; D000367:Age Factors; D000375:Aging; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001362:Avoidance Learning / Q000502:physiology; D002540:Cerebral Cortex / Q000201:enzymology* / Q000378:metabolism; D005080:Exercise Test; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology*; D008297:Male; D010805:Physical Conditioning, Animal / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat; D000072198:ADAM17 Protein
keywords: Aging; Amyloid precursor protein; BACE; Hippocampus; Prefrontal cortex; TACE