title: Comparing the effects of two neurotoxins in cortical astrocytes obtained from rats of different ages: involvement of oxidative damage.
abstract: Oxidative stress has been recognized as a potential mediator of cell death. Astrocytes play an active role in brain physiology responding to harmful stimuli by activating astrogliosis, which in turn has been associated either with survival or degenerative events. The characterization of the mechanistic actions exerted by different toxins in astrocytes is essential to understand the brain function and pathology. As age plays a critical role in degenerative processes, the aim of this study was to determine whether the administration of equimolar concentrations of two neurotoxins evoking different toxic patterns can induce differential effects on primary astrocytes obtained either from newborn or adult rats, with particular emphasis on those events linked to oxidative stress as a potential source of damage. Primary cortical astrocyte cultures derived from rat brains were exposed to 1-methyl-4-phenylpyridinium (MPP+) or beta-amyloid peptide (β-amyloid). Mitochondrial functionality and cell viability were determined as physiological parameters, whereas lipid and protein oxidation were used as markers of oxidative damage. The results of these experiments pointed towards a higher vulnerability to MPP + over β-amyloid, on most of the tested markers. Hence, in order to allow a comprehensive evaluation of astrocytic responses against MPP + intoxication, a third astrocyte group was included for dose-response experiments: astrocytes derived from aged rats. The present data indicate that the differences associated with age were mainly found in astrocytes exposed to MPP + (25 and 50 μM) at 1-h treatment. Results are discussed in terms of the differential mechanisms involved in each model.
authors.affiliation: Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana Iztapalapa, México, D.F. 09340, Mexico.
authors.forename: Adriana
authors.initials: A
authors.lastname: Alarcón-Aguilar
authors.forename: Viridiana Yazmín
authors.initials: VY
authors.lastname: González-Puertos
authors.forename: Armando
authors.initials: A
authors.lastname: Luna-López
authors.forename: Ambar
authors.initials: A
authors.lastname: López-Macay
authors.forename: Julio
authors.initials: J
authors.lastname: Morán
authors.forename: Abel
authors.initials: A
authors.lastname: Santamaría
authors.forename: Mina
authors.initials: M
authors.lastname: Königsberg
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000375:Aging; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D015655:1-Methyl-4-phenylpyridinium
keywords: MPP+; astrocyte primary cultures; cytotoxicity; oxidative stress; β-amyloid peptide