Further studies of the effects of aging on arginine metabolites in the rat vestibular nucleus and cerebellum

P Liu; N Gupta; Y Jing; N D Collie; H Zhang; P F Smith

doi:10.1016/j.neuroscience.2017.02.033

Further studies of the effects of aging on arginine metabolites in the rat vestibular nucleus and cerebellum

Neuroscience. 2017 Apr 21:348:273-287. doi: 10.1016/j.neuroscience.2017.02.033. Epub 2017 Feb 24.

Authors

P Liu¹, N Gupta², Y Jing², N D Collie², H Zhang³, P F Smith⁴

Affiliations

¹ Dept. of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand; The Brain Research New Zealand Centre of Research Excellence, New Zealand. Electronic address: ping.liu@otago.ac.nz.
² Dept. of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
³ School of Pharmacy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
⁴ Dept. of Pharmacology and Toxicology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand; The Brain Research New Zealand Centre of Research Excellence, New Zealand; The Eisdell Moore Centre, University of Auckland, New Zealand.

PMID: 28238850
DOI: 10.1016/j.neuroscience.2017.02.033

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.

Keywords: GABA; aging; arginine metabolites; cerebellum; glutamate; vestibular nucleus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / metabolism*
Animals
Arginine / metabolism*
Cerebellum / metabolism*
Citrulline / metabolism
Glutamic Acid / metabolism
Male
Nitric Oxide Synthase / metabolism
Ornithine / metabolism
Rats
Rats, Sprague-Dawley
Vestibular Nuclei / metabolism*

Substances

Citrulline
Glutamic Acid
Arginine
Ornithine
Nitric Oxide Synthase