Neuronal nitric oxide synthase expression in the cochlear nucleus in a salicylate model of tinnitus.
Although a number of studies suggest that the development of tinnitus is associated with hyperactive neuronal discharges in the brainstem cochlear nucleus (CN), there is relatively little evidence to indicate the neurochemical basis of this phenomenon. While some studies suggest that it may be partly due to a decrease in GABAergic inhibition, it is also possible that increased excitability is a contributing factor. In the current study, we investigated whether the salicylate animal model of tinnitus is associated with changes in the number of CN neurons expressing neuronal nitric oxide synthase (nNOS), one of the NOS isoforms that results in the production of the neurotransmitter, nitric oxide. We used a behavioral conditioning paradigm to confirm that animals receiving salicylate injections experienced tinnitus, and used immunohistochemistry with stereology to quantify the number of nNOS-expressing neurons in the dorsal and ventral CN (DCN and VCN, respectively) in salicylate- and vehicle control-treated animals. We also employed Western blotting to quantify the amount of nNOS protein expression in the total CN (i.e., the DCN and VCN together). We found a significant increase (of approximately 70%) in the number of nNOS-expressing principal neurons in the VCN of salicylate-treated animals compared to controls, with no significant differences in the DCN; nor did we find any significant difference in the overall level of nNOS protein in the total CN using Western blotting. These results suggest that changes in the number of neurons in the VCN expressing nNOS may be implicated in the mechanisms of tinnitus.
Zheng
Yiwen
Y
Dept. of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.
Seung Lee
Hee
H
Smith
Paul F
PF
Darlington
Cynthia L
CL
D000818:Animals; D017626:Cochlear Nucleus / Q000166:cytology / Q000201:enzymology* / Q000503:physiopathology; D005108:Extinction, Psychological; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000201:enzymology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates; D014012:Tinnitus / Q000139:chemically induced / Q000201:enzymology*
D012459:Salicylates; D052248:Nitric Oxide Synthase Type I