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Abstract
Some studies have demonstrated that aging is associated with impaired vestibular reflexes,
especially otolithic reflexes, resulting in postural instability. However, the neurochemical
basis of these age-related changes is still poorly understood. The l-arginine metabolic
system has been implicated in changes in the brain associated with aging. In the current
study, we examined the levels of l-arginine and its metabolizing enzymes and downstream
metabolites in the vestibular nucleus complex (VNC) and cerebellum (CE) of rats with
and without behavioral testing which were young (4months old), middle-aged (12months
old) or aged (24months old). We found that aging was associated with lower nitric
oxide synthase activity in the CE of animals with testing and increased arginase in
the VNC and CE of animals with testing. l-citrulline and l-ornithine were lower in
the VNC of aged animals irrespective of testing, while l-arginine and l-citrulline
were lower in the CE with and without testing, respectively. In the VNC and CE, aging
was associated with lower levels of glutamate in the VNC, irrespective of testing.
In the VNC it was associated with higher levels of agmatine and putrescine, irrespective
of testing. In the CE, aging was associated with higher levels of putrescine in animals
without testing and with higher levels of spermine in animals with testing, and spermidine,
irrespective of testing. Multivariate analyses indicated significant predictive relationships
between the different variables, and there were correlations between some of the neurochemical
variables and behavioral measurements. Cluster analyses revealed that aging altered
the relationships between l-arginine and its metabolites. The results of this study
demonstrate that there are major changes occurring in l-arginine metabolism in the
VNC and CE as a result of age, as well as behavioral activity.