Hippocampal nitric oxide synthase and arginase and age-associated behavioral deficits

Abstract

The present study investigated age-related changes in nitric oxide synthase (NOS) and arginase in the subregions of the hippocampus and their correlations with animals' performance in the open field, T-maze, and water maze tasks. Aged rats (24 months old) showed reduced exploratory activity and poorer spatial learning relative to the young adults (4 months old). Significant increases in total NOS activity were found in the aged dentate gyrus and a dramatic decrease in endothelial NOS expression was observed in the aged CA2/3. Activity or protein expression of inducible NOS was not detected in any subregion of the hippocampus. There were no age-related changes in total arginase activity or arginase I and arginase II protein expression. Correlation analysis revealed that animals' motor ability was associated with CA1 NOS and arginase, as well as hippocampal function. The present findings provide further support for the involvement of NOS/NO and arginase in the normal aging process. A strong positive correlation between CA1 eNOS protein expression and swimming speed in the water maze task may reflect a relationship between the local cerebral blood flow and neuronal activity.

Interactions between Nitric Oxide and Corticosterone in the Regulation of Progenitor Cell Proliferation in the Dentate Gyrus of the Adult Rat

“…The results in this paper suggest that at least one way that glucocorticoids may reduce proliferation is by increasing the expression of iNOS and/or eNOS. iNOS has very low expression in the dentate gyrus of control animals (Liu et al, 2005), but is markedly stimulated by excess corticosterone. Interestingly nNOS, the neural form of NO, was not altered by such treatment, although whether Figure 7 Effect of L-NAME on Ki-67-labeled cell counts in adrenalectomized (ADX) rats implanted with one 30% s.c. corticosterone pellets and receiving either additional (2 mg/kg/day) corticosterone or seasame oil daily at 1000 h for 12 days.…”

Age-related changes in nitric oxide synthase in the lateral geniculate nucleus of rats

“…By Western blotting brain extracts, Uttenthal et al (1998) observed a several-fold increase in NOSpositive bands in aged rats. In addition, Liu and co-workers (Liu et al 2003(Liu et al , 2004(Liu et al , 2005 reported increased activity in the hippocampus and prefrontal cortex of aged rats. Yu et al (2006) showed a significant rise in NADPH-d activity in the supraoptic nucleus of aged rats consistent with the increased NADPH-d activity seen in the present report.…”

Cyclic GMP and Nitric Oxide Synthase in Aging and Alzheimer's Disease

“…Available data indicated enhanced mRNA levels, no alteration in protein level and decreased activity [57]. Significant decrease in the eNOS protein level during aging was presented by Liu et al [36] in CA2/CA3 layer of hippocampus but not across the dorsal and ventral hippocampus and no changes in the other investigated brain parts [34,35]. However, the eNOS activity was not determined, and the alteration of protein level can only suggest lower eNOS activity.…”

“…Liu et al [34] and La Porta and Comolli [32] demonstrated also an increase in nNOS activity in the aged brain. In their last few studies, Liu et al [34][35][36] support the contribution of NOS/NO to aging. Their data indicated a significant increase in the total NOS activity in aged dentate gyrus of hippocampus and in the other investigated brain parts as compared with younger rats with no change in nNOS protein levels.…”