Department of Pharmacology, Faculty of Pharmacy, University of Aleppo, P.O. Box. 8119, Aleppo, Syria.
J Mol Neurosci. 2012 Jan;46(1):145-52. doi: 10.1007/s12031-011-9539-x. Epub 2011 May 12.
The changes in the mRNA levels of α(2A) and α(2C) adrenoceptors were investigated in unilateral 6-OHDA-lesioned rat model of Parkinson's disease and L: -DOPA-induced dyskinesia using in situ hybridization. In the untreated 6-OHDA-lesioned rats, α(2A) expression was elevated in the locus coeruleus (160 ± 8% and 142 ± 8% in lesioned and unlesioned sides compared to the comparable side in sham-operated rats). Following long-term (21 days, twice daily) treatment with L: -DOPA (25 mg/kg L: -DOPA methyl ester plus benserazide 6.25 mg/kg) in 6-OHDA-lesioned rats, levels of α(2A) adrenoceptor mRNA in the locus coeruleus were decreased, compared to the 6-OHDA-lesioned rats, returning to the levels of α(2A) mRNA in the sham-operated rats. α(2A) adrenoceptor expression was not changed in other brain regions in any treatment group. There was no change in α(2C) expression in the rostral or caudal striatum in which the highest density of α(2C) mRNA is present. In conclusion, the data presented in this study demonstrate an increase in α(2A) adrenoceptor mRNA in the locus coeruleus in the 6-OHDA-lesioned rat model of Parkinson's disease. In addition, the data show that repeated treatment with L: -DOPA in 6-OHDA-lesioned rats, which induces dyskinesia, restores α(2A) mRNA levels. These changes of α(2A) mRNA expression, observed in the locus coeruleus, might be of importance to basal ganglia transmission and motor function.
本研究采用原位杂交技术,研究了单侧 6-羟多巴胺(6-OHDA)损毁帕金森病大鼠模型和左旋多巴(L: -DOPA)诱导的异动症中 α(2A)和 α(2C)肾上腺素能受体 mRNA 水平的变化。在未经治疗的单侧 6-OHDA 损毁大鼠中,蓝斑核中 α(2A)的表达升高(损毁侧与未损毁侧相比,分别升高了 160±8%和 142±8%,而假手术组的相应侧则升高了 160±8%和 142±8%)。在连续 21 天(每天两次)给予 L: -DOPA(25 mg/kg L: -DOPA 甲酯加 6.25 mg/kg 苯甲丝肼)治疗后,与单侧损毁大鼠相比,蓝斑核中的 α(2A)肾上腺素能受体 mRNA 水平降低,与假手术大鼠的 α(2A)mRNA 水平相当。在任何治疗组中,其他脑区的 α(2A)受体表达均未改变。在纹状体的头尾部(此处存在最高密度的 α(2C)mRNA),α(2C)表达也没有变化。综上所述,本研究的数据表明,帕金森病单侧 6-OHDA 损毁大鼠模型蓝斑核中的 α(2A)肾上腺素能受体 mRNA 表达增加。此外,研究还表明,在单侧损毁大鼠中反复给予 L: -DOPA 治疗(引起异动症)可以恢复 α(2A)mRNA 水平。这些在蓝斑核中观察到的 α(2A)mRNA 表达变化,可能对基底节的传递和运动功能具有重要意义。