title: The role of NOS in the impairment of spatial memory and damaged neurons in rats injected with amyloid beta 25-35 into the temporal cortex.
abstract: The Aβ(25-35) fraction mimics the toxic effects of the complete peptide Aβ(1-42) because this decapeptide is able to cause memory impairment and neurodegenerative events. Recent evidence has shown that the injection of Aβ(25-35) into the temporal cortex (TCx) of the rat increases the nitric oxide (NO) pathways with several consequences, such as neuronal loss in rats. Our aim was to investigate the effects of each NOS isoform by the prior injection of NOS inhibitors before the injection of the Aβ(25-35). One month after the treatment, the animals were tested for their spatial memory in the radial maze. The hippocampus (Hp) and TCx were assessed for NO production, nitration of proteins (3-NT), astrocytosis (GFAP), and neuronal loss. Our findings show a significant impairment in the memory caused by Aβ25-35 injection. In contrast NOS inhibitors plus Aβ25-35 cause a protection yielding a high performance in the memory test and reduction of cell damage in the TCx and the Hp. Particularly, iNOS is the major source of NO and related to the inflammatory response leading to the memory deficits. The inhibition of iNOS is an important target for neuronal protection against the toxicity of the Aβ25-35 over the long term.
authors.affiliation: Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72570, Mexico.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Diaz
authors.forename: Liliana
authors.initials: L
authors.lastname: Mendieta
authors.forename: Edgar
authors.initials: E
authors.lastname: Zenteno
authors.forename: Jorge
authors.initials: J
authors.lastname: Guevara
authors.forename: Ilhuicamina Daniel
authors.initials: ID
authors.lastname: Limon
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology*; D008569:Memory Disorders / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013702:Temporal Lobe / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D006146:Guanidines; D007191:Indazoles; D009566:Nitrates; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester