Citation

Shin SS, Bray ER, Zhang CQ, Dixon CE. Brain Res. 2011; 1369: 208-215.

Copyright

(Copyright © 2011, International Brain Research Organization, Publisher Elsevier Publishing)

DOI

10.1016/j.brainres.2010.10.096

PMID

21047500

PMCID

PMC3014391

Abstract

There is increasing evidence that traumatic brain injury (TBI) induces hypofunction of the striatal dopaminergic system, the mechanisms of which are unknown. In this study, we analyzed the activity of striatal tyrosine hydroxylase (TH) in rats at 1 day, 1 week, and 4 weeks after TBI using the controlled cortical impact model. There were no changes in the level of TH phosphorylated at serine 40 site (pser40TH) at 1 day or 4 weeks. At 1 week, injured animals showed decreased pser40TH to 73.9 ± 7.3% (p≤0.05) of sham injured rats. The in vivo TH activity assay showed no significant difference between injured and sham rats at 1 day. However, there was a decreased activity in injured rats to 62.1 ± 8.2% (p≤0.05) and 68.8 ± 6.2% (p≤0.05) of sham injured rats at 1 and 4 weeks respectively. Also, the activity of protein kinase A which activates TH, decreased at 1 week (injured: 87.8 ± 2.8%, sham: 100.0 ± 4.2%, p≤0.05). To study the release activity of dopamine after injury, potassium (80mM) evoked dopamine release was measured by microdialysis in awake, freely moving rats. Dialysates were collected and analyzed by high performance liquid chromatography. There were no significant differences in dopamine release at 1 day and 4 weeks between sham and injured groups. At 1 week, there was a significant decrease (injured: 0.067 ± 0.015 μM, sham: 0.127 ± 0.027 μM, p≤0.05). These results suggest that TBI-induced dopamine neurotransmission deficits are, at least in part, attributable to deficits in TH activity.

Language: en