title: 1,25-Dihydroxyvitamin D3 exerts neuroprotective effects in an ex vivo model of mild hyperhomocysteinemia.
abstract: Elevated plasma homocysteine (Hcy) levels have been detected in patients with various neurodegenerative conditions. Studies of brain tissue have revealed that hyperhomocysteinemia may impair energy metabolism, resulting in neuronal damage. In addition, new evidence has indicated that vitamin D plays crucial roles in brain development, brain metabolism and neuroprotection. The aim of this study was to investigate the neuroprotective effects of 1,25-dihydroxivitamin D3 (calcitriol) in cerebral cortex slices that were incubated with a mild concentration of Hcy. Cerebral cortex slices from adult rats were first pre-treated for 30 min with one of three different concentrations of calcitriol (50 nM, 100 nM and 250 nM), followed by Hcy for 1h to promote cellular dysfunction. Hcy caused changes in bioenergetics parameters (e.g., respiratory chain enzymes) and mitochondrial functions by inducing changes in mitochondrial mass and swelling. Here, we used flow cytometry to analyze neurons that were double-labelled with Propidium Iodide (PI) and found that Hcy induced an increase in NeuN(+)/PI cells but did not affect GFAP(+)/Pi cells. Hcy also induced oxidative stress by increasing reactive oxygen species generation, lipid peroxidation and protein damage and reducing the activity of antioxidant enzymes (e.g., SOD, CAT and GPx). Calcitriol (50 nM) prevented these alterations by increasing the level of the vitamin D receptor. Our findings suggest that using calcitriol may be a therapeutic strategy for treating the cerebral complications caused by Hcy.
authors.affiliation: Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Longoni
authors.affiliation: Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Janaina
authors.initials: J
authors.lastname: Kolling
authors.affiliation: Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Tiago M
authors.initials: TM
authors.lastname: dos Santos
authors.affiliation: Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
authors.forename: João Paulo
authors.initials: JP
authors.lastname: dos Santos
authors.affiliation: Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Jussemara Souza
authors.initials: JS
authors.lastname: da Silva
authors.affiliation: Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Letícia
authors.initials: L
authors.lastname: Pettenuzzo
authors.affiliation: Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
authors.affiliation: Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Adriano M
authors.initials: AM
authors.lastname: de Assis
authors.affiliation: Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Quincozes-Santos
authors.affiliation: Postgraduate Program in Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil. Electronic address: wyse@ufrgs.br.
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D042963:Electron Transport Complex II / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005434:Flow Cytometry; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011419:Propidium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D006710:Homocysteine; D011419:Propidium; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D010751:Phosphopyruvate Hydratase; D000254:Sodium-Potassium-Exchanging ATPase; D002117:Calcitriol
keywords: 1,25-Dihydroxyvitamin D3; Calcitriol; Mild hyperhomocysteinemia; Neuroprotection; Vitamin D receptor