The effect of glucocorticoids on bradykinesia induced by immobilization stress.
It is well known that the release of glucocorticoids from the adrenal gland is increased in response to many types of stressors and plays a principal role in stress responses. We have shown that the synthesis of prostaglandins (PGs) in the brain is increased under several stress conditions including immobilization (IMO), and that endogenous glucocorticoids counteract this stress-induced PG synthesis. It was also recently reported that IMO damages dopaminergic (DA) neurons in the substantia nigra (SN), which is known to cause symptoms similar to Parkinson's disease (PD). The present study was therefore undertaken to determine the role of glucocorticoids in modulating the signs of PD induced by IMO. The pole test, in which each mouse was placed head upward at the top of a pole and the time taken to turn downward and to arrive on the floor was recorded, and immunohistochemistry for tyrosine hydroxylase (TH) in the SN were performed to evaluate bradykinesia and injury of DA neurons, respectively. Intact and adrenalectomized (ADX) mice were immobilized for 2 h twice, 1 day apart. Both bradykinesia and a decrease in the number of TH-immunoreactive cells in the SN were observed in ADX mice, but not in intact mice, following IMO. These effects of IMO on ADX mice were restored by treatment with corticosterone or indomethacin, a PG synthesis inhibitor. These results suggest that glucocorticoids play a role in preventing the detrimental effect of IMO on nigral DA neurons and resulting bradykinesia, and that this effect of IMO involves PG-mediated mechanisms.
Matsuwaki
Takashi
T
Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Yamanouchi
Keitaro
K
Nishihara
Masugi
M
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000097:blood; D005080:Exercise Test; D005938:Glucocorticoids / Q000494:pharmacology*; D018476:Hypokinesia / Q000097:blood / Q000209:etiology*; D007103:Immobilization / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D013315:Stress, Psychological / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D005938:Glucocorticoids; D014446:Tyrosine 3-Monooxygenase; D003345:Corticosterone