Effect of ageing on tissue levels of amino acids involved in the nitric oxide pathway in rat brain

Abstract

Nitric oxide (NO) and citrulline are produced from L-arginine by the action of NO synthase after activation of excitatory amino acid receptors. In addition to its role in neurodegeneration, there is convincing evidence that NO is also involved in long-term potentiation, a cellular analog of learning and memory in the mammalian nervous system. In the present study, concentrations of L-arginine, citrulline, aspartic acid and glutamic acid were determined in various brain regions of young and old rats. The aim was to examine whether changes in brain concentrations of these amino acids might be indicative of a possible decrease in NO production with ageing, in relation with the well-established decline of cognitive function. Brain aspartic acid, citrulline and L-arginine concentrations were found to be lower in old rats compared to young animals, although the decrease did not always reach statistical significance. In contrast, no change in glutamic acid levels was found. In all brain structures of young and old rats, concentrations of L-arginine were higher than the concentration for NO synthase to function at maximum velocity in the rat brain. Therefore, the decrease in citrulline concentrations found in some brain regions of old rats might be seen, at least partly, as a reflection of a lower production of NO with ageing, although further work is clearly needed to ascertain a decrease in rat brain NO synthase activity with age.

Simultaneous Measurement of Nitrite and Nitrate Levels as Indices of Nitric Oxide Release in the Cerebellum of Conscious Rats

“…To rule out the contribution of pressor effects of this compound, further studies should be performed using more specific neuronal NOS inhibitors that do not have pressor effects. An interesting finding in the present study was that the intraperitoneal injection as well as the direct infusion of L-Arg into the cerebellum through a dialysis probe produced a persistent increase in NO2 and NO3 -levels, although it has been suggested that NOS may be saturated with L-Arg in the brain because L-Arg levels in the brain are far above the Km value of NOS for L-Arg (Strolin Benedetti et a!., 1993). It has been shown that L-Arg is predominantly located in the glial cells in the brain (Aoki et al, 1991) and that the release of L-Arg occurs after electrical white matter stimulation in rat cerebellar slices in vitro (Hansel et a!., 1992) and in the thalamus after physiological stimulation of afferents in vivo (Do et al, 1994).…”

Late-onset “white cord syndrome” in an elderly patient after posterior cervical decompression and fusion: a case report

“…We postulate that the delay of the clinical manifestation in our elderly male patient was due to the endothelial damage and atherosclerosis caused by chronic hypertension. There have been reports of a decline in the nitric oxide (NO) precursors such as aspartic acid, citrulline, and arginine as well as an age-dependent decrease in endotheliumdependent relaxation, which is thought to be mediated by NO [22]. This led to subacute reperfusion to the compressed spinal cord area, resulting to this late-onset case of WCS.…”

Inflammatory and Hemodynamic Changes in the Cerebral Microcirculation of Aged Rats after Global Cerebral Ischemia and Reperfusion

“…Multiple factors could contribute to altered cerebral blood-flow regulation in the aged brain. For example, endothelial cell nitric oxide (NO) production and the subsequent regulation of vascular tone are reduced in the vasculature of the aged brain (6,11,38). Moreover, decreased NO also enhances PMN adhesion to the cerebral microcirculation after I-R (18,27,48).…”