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.

摘要

The Abeta(25-35) fraction mimics the toxic effects of the complete peptide Abeta(1-42) because this decapeptide is able to cause memory impairment and neurodegenerative events. Recent evidence has shown that the injection of Abeta(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 Abeta(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 Abeta25-35 injection. In contrast NOS inhibitors plus Abeta25-35 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 Abeta25-35 over the long term.