Abstract
The aim of this study was to examine the effects of intrastriatally injected nitric oxide synthase (NOS) inhibitors, Nω-nitro-l-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), on quinolinic acid (QA)-induced toxicity in selective vulnerable brain regions of adult Wistar rats. QA was administered into the striatum unilaterally, in a single dose of 150 nM/L with a stereotaxic instrument. The other two experimental groups were pretreated with L-NAME and 7-NI, respectively. The control group of animals was treated with 0.154 mM/L saline solution. The animals were decapitated seven days after the treatment. Samples of both striatum and forebrain cortex were prepared for measurement of acetylcholinesterase (AChE) activity. QA injection revealed a significant increase in AChE activity in both the ipsi- and contralateral striatum and forebrain cortex compared to the control animals. Treatment with NOS inhibitors, followed by QA, very clearly demonstrated lower levels of AChE bilaterally in these brain structures, compared to the QA-treated group.
Highlights
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder marked by selective striatal degeneration, motor dysfunction and cognitive deterioration with learning impairment, memory loss and dementia (Beister et al, 2004)
Our studies have indicated that acute intrastriatal injections of the endogenous N-methyl-D-aspartate (NMDA) receptor agonist, quinolinic acid (QA), can mimic some of the neuroanatomical and behavioral deficits of HD (Maksimović et al, 2002)
The AChE activity obtained in the forebrain cortex (Fig, 2) was similar: significantly increased activity of AChE in both the ipsi- (p
Summary
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder marked by selective striatal degeneration, motor dysfunction and cognitive deterioration with learning impairment, memory loss and dementia (Beister et al, 2004). Intrastriatal injections of QA have been shown to produce an HD-like pattern of neurodegeneration, including loss of striatal projection neurons (Armstrong et al, 2000). HD is characterized by the loss of neurons in the basal forebrain cholinergic cells that project to the cerebral cortex and hippocampus (Smith et al, 2006). These impairments have been correlated with the memory loss noted in the dementia of HD. This “cholinergic hypothesis” has led to the rational design of drugs to enhance or stimulate acetylcholine (ACh)mediated neurotransmission (Walker et al, 2011)
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