Age-related reductions in the activities of antioxidant enzymes in the rat inferior colliculus.
The inferior colliculus (IC) is a major relay and processing center of auditory signals in the midbrain and receives inputs from most other auditory nuclei. A number of studies have indicated age-related declines in the GABAergic and excitatory amino acid systems in the IC, including losses in both GABA immunoreactive (+) and GABA immunonegative (-) synapses. The goal of this project was to identify potential biochemical and morphological changes in the IC that may contribute to deficits in the functions of these neurotransmitters, using three age groups of Fischer-344 rats. Homogenates obtained from the IC showed age-dependent reductions in activities of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), with a concomitant increase in lipid peroxidation. Dephosphorylation of IC homogenates with alkaline phosphatase reduced the activities of SOD and CAT in all age groups, which could be restored by protein kinase C (PKC)-dependent phosphorylation. Restoration of enzyme activity was specific to the PKC-alpha isozyme, but not to the beta1, beta2, delta or gamma forms. No age-dependent change in the levels of PKC isoforms (alpha, beta1, beta2 and gamma) was detectable in IC homogenates. Morphological analyses indicate decreases in mitochondrial density in the somata of both GABA+ and GABA- IC neurons in 19- and 28-month-old rats when compared to 3-month-olds, along with significantly higher matricial abnormalities. These data indicate age-related increases in oxidative stress in the IC, which could be partially restored by PKC. The progressive increase in oxidative stress with age may underlie changes in neuronal morphology and function of the IC.
Mei
Y
Y
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62794, USA.
Gawai
K R
KR
Nie
Z
Z
Ramkumar
V
V
Helfert
R H
RH
D000375:Aging / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001306:Auditory Pathways / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D002374:Catalase / Q000378:metabolism; D007245:Inferior Colliculi / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D007527:Isoenzymes / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D018384:Oxidative Stress; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051571:Protein Kinase C-alpha; D051381:Rats; D011916:Rats, Inbred F344; D013482:Superoxide Dismutase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000975:Antioxidants; D007527:Isoenzymes; D005680:gamma-Aminobutyric Acid; D002374:Catalase; D013482:Superoxide Dismutase; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D000469:Alkaline Phosphatase