title: Increased expression of Aquaporin 4 in the rat hippocampus and cortex during trimethyltin-induced neurodegeneration.
abstract: Trimethyltin chloride (TMT) is a neurotoxicant producing neuronal degeneration and reactive astrogliosis in the mammalian central nervous system, especially the hippocampus. A previous magnetic resonance imaging investigation in TMT-treated rats evidenced dilation of lateral ventricles, also suggesting alterations in blood-brain barrier permeability and brain edema. Aquaporin 4 (AQP4), a glial water channel protein expressed mainly in the nervous system, is considered a specific marker of vascular permeability and thought to play an important role in brain edema (conditions). We studied AQP4 expression in the hippocampus and cerebral cortex of TMT-treated rats in order to explore the molecular mechanisms involved in brain edema occurring in these experimental conditions. Real-time PCR and western blotting data showed significant up-regulation of both AQP4 mRNA and protein levels starting 14 days after TMT treatment in the hippocampus and cortex. Parallel immunofluorescence studies indicated intense astrogliosis and AQP4 immunoreactivity diffusely pronounced in the hippocampal and cortex areas starting 14 days after TMT intoxication. In order to study the effects of TMT on vascular integrity, double-label immunofluorescence experiments for rat immunoglobulin G (IgG) and rat endothelial cell antigen-1 (RECA-1) or neuronal nuclei (NeuN) (endothelial and neuronal markers respectively) were performed. The results indicated, at 21 and 35 days after treatment, the presence of rat IgG in paravasal parenchyma and in some neuronal cells of the hippocampus and cortex. The extravasated IgG staining was temporally correlated with over-expression of neuronal vascular endothelial growth factor (VEGF) and the active phosphorylated form of its neuronal receptor (VEGFR-2P), suggesting that these factors may cooperate in mediating vascular leakage.
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, L. go F. Vito 1, 00168 Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ceccariglia
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, L. go F. Vito 1, 00168 Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: D'altocolle
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, L. go F. Vito 1, 00168 Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Del Fa'
authors.affiliation: Institute of Biochemistry and Clinical Chemistry, Università Cattolica del Sacro Cuore, L. go F. Vito 1, 00168 Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Silvestrini
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, L. go F. Vito 1, 00168 Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Barba
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, L. go F. Vito 1, 00168 Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pizzolante
authors.affiliation: Institute Pasteur de Lille, Lille2 University, rue du Professeur Laguesse, 59000 Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Repele
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, L. go F. Vito 1, 00168 Rome, Italy. Electronic address: fabrizio.michetti@rm.unicatt.it.
authors.forename: F
authors.initials: F
authors.lastname: Michetti
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, L. go F. Vito 1, 00168 Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Gangitano
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D051401:Aquaporin 4 / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D014298:Trimethyltin Compounds; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C546339:Rbfox3 protein, rat; D014298:Trimethyltin Compounds; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C040533:trimethyltin chloride; C000602029:Kdr protein, rat; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Aquaporin 4; cortex; hippocampus; neurodegeneration; trimethyltin; vascular endothelium growth factor