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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

Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72570, Mexico.
Pharmacology Biochemistry and Behavior (Impact Factor: 2.82). 03/2011; 98(1):67-75. DOI: 10.1016/j.pbb.2010.12.005
Source: PubMed

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.

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    • "Therefore, in our study it is reasonable to expect that infusion of 1400 W, following the water maze training, blocked iNOS-induced memory impairment, thereby leading to the observed improvements in spatial memory. In fact, there are extensive evidences suggesting that NOS inhibitors, such as 1400 W, can postpone the onset or minimize the neurodegeneration (Diaz et al., 2011; Tabrizian et al., 2010). "
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    • "Our results shows that spatial learning and memory were delayed in animals injected with A␤ (25–35) compared to the control group because the percent correct response was lower Furthermore , the A␤ (25–35) -treated animals had a larger number of RWs and MWs in the learning test. These findings indicate that injection of A␤ (25–35) into the Hp causes impairment of spatial memory in rats over the long term as suggested by other workers that injection of A␤ (25–35) causes a cognitive impairment and neuronal damage [3] [7] [8] [13]. "
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