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Hyperhomocysteinemia selectively alters expression and stoichiometry of intermediate filament and induces glutamate‐ and calcium‐mediated mechanisms in rat brain during development
Author(s) -
Loureiro Samanta Oliveira,
Heimfarth Luana,
Lima Pelaez Priscila,
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,
Souza Wyse Angela Terezinha,
PessoaPureur Regina
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2009.10.002
Subject(s) - neurofilament , glutamate receptor , glial fibrillary acidic protein , hippocampus , hippocampal formation , medicine , biology , ionotropic effect , microbiology and biotechnology , endocrinology , cerebral cortex , metabotropic glutamate receptor , neuroscience , chemistry , receptor , biochemistry , immunohistochemistry
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 500 μM 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 Ca 2+ 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.