Traumatic brain injury reduces striatal tyrosine hydroxylase activity and potassium-evoked dopamine release in rats.
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 (80 mM)-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.
Brain Trauma Research Center, Department of Neurosurgery, University of Pittsburgh, 3434 Fifth Ave, Suite 201, Pittsburgh, PA 15260, USA.
Samuel S
SS
Shin
Eric R
ER
Bray
Cathy Q
CQ
Zhang
C Edward
CE
Dixon
D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000293:injuries / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D014446:Tyrosine 3-Monooxygenase; D011188:Potassium; D004298:Dopamine