Effects of L-arginine and Nω-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats

Abstract

Nitric oxide (NO) is a novel type of neurotransmitter that is closely associated with synaptic plasticity, learning and memory. In the present study, we assessed the effects of L-arginine and N ω -nitro-Larginine methylester (L-NAME, a nitric oxide synthase inhibitor) on learning and memory. Rats were assigned to three groups receiving intracerebroventricular injections of L-Arg (the NO precursor), L-NAME, or 0.9% NaCl (control), once daily for seven consecutive days. Twelve hours after the last injection, they underwent an electric shock-paired Y maze test. Twenty-four hours later, the rats' memory of the safe illuminated arm was tested. After that, the levels of NO and α7 nicotinic acetylcholine receptor (α7 nAChR) in the prefrontal cortex and hippocampus were assessed using an NO assay kit, and immunohistochemistry and Western blots, respectively. We found that, compared to controls, L-Arg-treated rats received fewer foot shocks and made fewer errors to reach the learning criterion, and made fewer errors during the memory-testing session. In contrast, L-NAME-treated rats received more foot shocks and made more errors than controls to reach the learning criterion, and made more errors during the memory-testing session. In parallel, NO content in the prefrontal cortex and hippocampus was higher in L-Arg-treated rats and lower in L-NAME rats, compared to controls. Similarly, α7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in L-Arg-treated rats and lower in L-NAME rats, compared to controls. These results suggest that the modulation of NO content in the brain correlates with α7 nAChR distribution and expression in the prefrontal cortex and hippocampus, as well as with learning and memory performance in the Y-maze.

Dysregulated Urinary Arginine Metabolism in Older Adults With Amnestic Mild Cognitive Impairment

“…Additionally, it is notable that an increase in bioavailable arginine negatively associates with water-maze performance as rats become aged (Cassel et al, 2005). Moreover, some previous studies of AD mouse models and patients also support that the supplementation of arginine could improve memory consolidation and learning (Calabro et al, 2013; Wei et al, 2013). In sum, these findings suggest that there is a likely relationship between dysregulated arginine metabolism and impairment in the maintenance of cognition.…”

Exercise-induced Nitric Oxide Contributes to Spatial Memory and Hippocampal Capillaries in Rats

“…In terms of the mechanism for the exercise-induced capillary changes in the hippocampus and the improvement in spatial memory ability, our recent results revealed that after 28 days of L-NAME injection, the endogenous NO content and enzymatic activity of NOS in the cortex of rats were significantly decreased, whereas the spatial learning and memory ability were decreased [32]. Previous studies have also reported similar findings that blocked NO production decreases spatial learning and memory ability [28,30,[49][50][51]. These results indicate that decreased endogenous NO content and enzymatic activity of NOS causes a decline in spatial learning and memory ability.…”

Cerebroprotein Hydrolysate-I Inhibits Hippocampal Neuronal Apoptosis by Activating PI3K/Akt Signaling Pathway in Vascular Dementia Mice

“…The method described by Zhang et al 23 and Wei et al 24 served as the reference. In the present study, a Y-maze electric stimulator (Institute of Materia Medica Chinese Academy of Medical Science) was used to train and test mice's learning and memory abilities.…”