title: Nucleoside triphosphate diphosphohydrolases role in the pathophysiology of cognitive impairment induced by seizure in early age.
abstract: Studies have shown that seizures in young animals lead to later cognitive deficits. There is evidence that long-term potentiation (LTP) and long-term depression (LTD) might contribute to the neural basis for learning and memory mechanism and might be modulated by ATP and/or its dephosphorylated product adenosine produced by a cascade of cell-surface transmembrane enzymes, such as E-NTPDases (ecto-nucleoside triphosphate diphosphohydrolases) and ecto-5'-nucleotidase. Thus, we have investigated if hippocampal ecto-nucleotidase activities are altered at different time periods after one episode of seizure induced by kainic acid (KA) in 7 days old rats. We also have evaluated if 90 day-old rats previously submitted to seizure induced by KA at 7 days of age presented cognitive impairment in Y-maze behavior task. Our results have shown memory impairment of adult rats (Postnatal day 90) previously submitted to one single seizure episode in neonatal period (Postnatal day 7), which is accompanied by an increased ATP hydrolysis in hippocampal synaptosomes. The metabolism of ATP evaluated by HPLC confirmed that ATP hydrolysis was faster in adult rats treated with KA in neonatal period than in controls. Surprisingly, the mRNA and protein levels as seen by PCR and Western blot, respectively, were not altered by the KA administration in early age. Since we have found an augmented hydrolysis of ATP and this nucleotide seems to be important to LTP induction, we could assume that impairment of memory and learning observed in adult rats which have experienced a convulsive episode in postnatal period may be a consequence of the increased ATP hydrolysis. These findings correlate the purinergic signaling to the cognitive deficits induced by neonatal seizures and contribute to a better understanding about the mechanisms of seizure-induced memory dysfunction.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Avenida Ramiro Barcelos, 2600 Anexo, 90035-000 Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: G P
authors.initials: GP
authors.lastname: Cognato
authors.forename: F C
authors.initials: FC
authors.lastname: Vuaden
authors.forename: L E B
authors.initials: LE
authors.lastname: Savio
authors.forename: B
authors.initials: B
authors.lastname: Bellaver
authors.forename: E
authors.initials: E
authors.lastname: Casali
authors.forename: M R
authors.initials: MR
authors.lastname: Bogo
authors.forename: D O G
authors.initials: DO
authors.lastname: Souza
authors.forename: J
authors.initials: J
authors.lastname: Sévigny
authors.forename: C D
authors.initials: CD
authors.lastname: Bonan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001081:Apyrase / Q000378:metabolism; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003072:Cognition Disorders / Q000201:enzymology* / Q000209:etiology; D003292:Convulsants / Q000633:toxicity; D015870:Gene Expression; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000502:physiology; D043583:Nucleoside-Triphosphatase / Q000378:metabolism*; D011755:Pyrophosphatases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D015703:Antigens, CD; D003292:Convulsants; D000255:Adenosine Triphosphate; D011755:Pyrophosphatases; C439652:nucleoside-triphosphate diphosphohydrolase 3; D043583:Nucleoside-Triphosphatase; D001081:Apyrase; C067869:CD39 antigen; D007608:Kainic Acid