A multivariate analysis of the effects of aging on glutamate, GABA and arginine metabolites in the rat vestibular nucleus

Aging is associated with neurochemical changes in the brain that result in impaired vestibular reflex function. We analysed the concentrations of 9 related neurochemicals (l-arginine, l-citrulline, l-ornithine, agmatine, putrescine, spermidine, spermine, glutamate and γ–aminobutyric acid (GABA)) in the vestibular nucleus of aged (24 months old) and young (4 month old) rats; the cerebellum was analysed for comparison. The effects of the housing conditions of the rats were also investigated. Age significantly affected the concentrations of the 9 neurochemicals in both the vestibular nucleus and cerebellum (P = 0.000). Housing did not have a significant effect and the interaction between age and housing was significant only for the vestibular nucleus (P = 0.03). For both the vestibular nucleus and cerebellum, linear discriminant functions were identified that significantly predicted whether the animals were 4 or 24 months old (P = 0.000). Using multiple regression analysis, only vestibular nucleus spermidine, spermine and l-arginine could be predicted from the other neurochemical variables with an adjusted R2 of >80%. Cluster analyses were performed to determine if the neurochemical variables formed distinct groups and whether this changed as a function of age. For the vestibular nucleus but not the cerebellum, the clusters were substantially different for the 24 month old and 4 month old animals.

Research highlights
► Age affected glutamate, GABA and arginine metabolites in the rat vestibular nucleus.
► Linear discriminant functions could reliably predict the animals’ age.
► Vestibular nucleus polyamines and L-arginine could be predicted using regression. Cluster analysis revealed differences for the young and aged vestibular nucleus.