title: Homocysteine Induces Glial Reactivity in Adult Rat Astrocyte Cultures.
abstract: Astrocytes are dynamic glial cells associated to neurotransmitter systems, metabolic functions, antioxidant defense, and inflammatory response, maintaining the brain homeostasis. Elevated concentrations of homocysteine (Hcy) are involved in the pathogenesis of age-related neurodegenerative disorders, such as Parkinson and Alzheimer diseases. In line with this, our hypothesis was that Hcy could promote glial reactivity in a model of cortical primary astrocyte cultures from adult Wistar rats. Thus, cortical astrocytes were incubated with different concentrations of Hcy (10, 30, and 100 μM) during 24 h. After the treatment, we analyzed cell viability, morphological parameters, antioxidant defenses, and inflammatory response. Hcy did not induce any alteration in cell viability; however, it was able to induce cytoskeleton rearrangement. The treatment with Hcy also promoted a significant decrease in the activities of Na+, K+ATPase, superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as in the glutathione (GSH) content. Additionally, Hcy induced an increase in the pro-inflammatory cytokine release. In an attempt to elucidate the putative mechanisms involved in the Hcy-induced glial reactivity, we measured the nuclear factor kappa B (NFκB) transcriptional activity and heme oxygenase 1 (HO-1) expression, which were activated and inhibited by Hcy, respectively. In summary, our findings provide important evidences that Hcy modulates critical astrocyte parameters from adult rats, which might be associated to the aging process.
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica, ICBS, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Bairro Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Longoni
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica, ICBS, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Bairro Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Bellaver
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica, ICBS, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Bairro Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Larissa Daniele
authors.initials: LD
authors.lastname: Bobermin
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica, ICBS, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Bairro Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Camila Leite
authors.initials: CL
authors.lastname: Santos
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica, ICBS, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Bairro Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Nonose
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica, ICBS, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Bairro Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Janaina
authors.initials: J
authors.lastname: Kolling
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica, ICBS, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Bairro Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Tiago M
authors.initials: TM
authors.lastname: Dos Santos
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica, ICBS, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Bairro Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Adriano M
authors.initials: AM
authors.lastname: de Assis
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica, ICBS, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Bairro Santa Cecília, Porto Alegre, RS, 90035-003, Brazil. andrequincozes@ufrgs.br.|Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. andrequincozes@ufrgs.br.
authors.forename: André
authors.initials: A
authors.lastname: Quincozes-Santos
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas: Bioquímica, ICBS, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Bairro Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.|Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Angela T S
authors.initials: ATS
authors.lastname: Wyse
mesh_terms: D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006710:Homocysteine / Q000633:toxicity*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D018836:Inflammation Mediators; D006710:Homocysteine
keywords: Cortical adult astrocytes; Heme oxygenase 1; Homocysteine; Inflammatory response; NFκB; Oxidative stress