title: Amino acid levels in some brain areas of inducible nitric oxide synthase knock out mouse (iNOS-/-) before and after pentylenetetrazole kindling.
abstract: Inducible nitric oxide synthase knock-out (iNOS(-/-)) mice are valid models of investigation for the role of iNOS in patho-physiological conditions. There are no available data concerning neuroactive amino acid levels of iNOS(-/-) mice and their behaviour in response to pentylenetetrazole (PTZ). We found no significant differences in the convulsive dose 50 (CD(50)) between iNOS(-/-) and control (iNOS(+/+)) mice, however, iNOS(-/-) mice reach the kindled status more slowly than control, suggesting that in basal condition the GABA-benzodiazepine inhibitory inputs are unaltered by iNOS mutation. Clear differences between iNOS(+/+) and iNOS(-/-) mice amino acid concentrations were evident both in basal conditions and after kindling. Our results show that aspartate was significantly lower in all brain areas studied except the brain stem whereas glutamate and glutamine were significantly higher in the cortex, hippocampus and brain stem. GABA was slightly and not significantly higher in the cortex, hippocampus and brain stem, whereas taurine was significantly higher in all areas except diencephalon and glycine was significantly lower in the diencephalon and cerebellum. In this context, the inability of iNOS(-/-) mice to increase the NO levels following PTZ administrations indicate that NO might play a pro-epileptogenic role in the genesis and development of some types of epilepsy. Since there is no correlation between neurotransmitter levels and the development of kindling, it is possible to exclude that the difference between the two strains is due to an imbalance between the considered neurotransmitters, and it is then possible that this difference is due to the presence of iNOS, which might be involved in long term plasticity of the brain.
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, School of Medicine, University of Messina, Messina, Italy. desarro@unicz.it
authors.forename: Grazia
authors.initials: G
authors.lastname: De Luca
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Di Giorgio
authors.forename: Salvatore
authors.initials: S
authors.lastname: Macaione
authors.forename: Pina Rita
authors.initials: PR
authors.lastname: Calpona
authors.forename: Eugenio Donato
authors.initials: ED
authors.lastname: Di Paola
authors.forename: Nicola
authors.initials: N
authors.lastname: Costa
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D003292:Convulsants; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D007696:Kindling, Neurologic; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010433:Pentylenetetrazole; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology; D013654:Taurine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000596:Amino Acids; D003292:Convulsants; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D013654:Taurine; D005680:gamma-Aminobutyric Acid; D052247:Nitric Oxide Synthase Type II; D010433:Pentylenetetrazole