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- Title
Hyperhomocysteinemia selectively alters expression and stoichiometry of intermediate filament and induces glutamate- and calcium-mediated mechanisms in rat brain during development
- Authors
Loureiro, Samanta Oliveira; Heimfarth, Luana; Pelaez, Priscila de Lima; Lacerda, Bruna Arcce; Vidal, Luiza Fedatto; Soska, Angela; Santos, Natália Gomes dos; Andrade, Cláudia; Tagliari, Bárbara; Scherer, Emilene B.S.; Guma, Fátima Therezinha Costa Rodrigues; Wyse, Angela Terezinha de Souza; Pessoa-Pureur, Regina
- Abstract
Abstract: The aim of the present work was to investigate the actions of a chemically induced chronic hyperhomocysteinemia model on intermediate filaments (IFs) of cortical and hippocampal neural cells and explore signaling mechanisms underlying such effects. Results showed that in hyperhomocysteinemic rats the expression of neural IF subunits was affected. In cerebral cortex, glial fibrillary acidic protein (GFAP) expression was donwregulated while in hippocampus high and middle molecular weight neurofilament subunits (NF-H and NF-M, respectively) were up-regulated. Otherwise, the immunocontent of IF proteins was unaltered in cerebral cortex while in hippocampus the immunocontent of cytoskeletal-associated low molecular weight neurofilament (NF-L) and NF-H subunits suggested a stoichiometric ratio consistent with a decreased amount of core filaments enriched in lateral projections. These effects were not accompanied by an alteration in IF phosphorylation. In vitro results showed that 500μM Hcy-induced protein phosphatases 1-, 2A- and 2B-mediated hypophosphorylation of NF subunits and GFAP in hippocampal slices of 17-day-old rats without affecting the cerebral cortex, showing a window of vulnerability of cytoskeleton in developing hippocampus. Ionotropic and metabotropic glutamate receptors were involved in this action, as well as Ca2+ release from intracellular stores through ryanodine receptors. We propose that the mechanisms observed in the hippocampus of 17-day-old rats could support the neural damage observed in these animals.
- Subjects
HOMOCYSTEINE; GENE expression; STOICHIOMETRY; CYTOPLASMIC filaments; GLUTAMIC acid; LABORATORY rats; NEURAL development; HIPPOCAMPUS (Brain); CALCIUM; PHOSPHATASES
- Publication
International Journal of Developmental Neuroscience, 2010, Vol 28, Issue 1, p21
- ISSN
0736-5748
- Publication type
Article
- DOI
10.1016/j.ijdevneu.2009.10.002