Brené S, Lindefors N, Persson H
Department of Medical Chemistry, Karolinska Institute, Stockholm, Sweden.
Brain Res Mol Brain Res. 1992 Jun;14(1-2):13-9. doi: 10.1016/0169-328x(92)90004-u.
Intracerebroventricular 6-hydroxydopamine injections were performed at postnatal days 3 and 6 in animals pretreated with the norepinephrine uptakeblocker desimipramine in order to generate a selective lesion of dopamine neurons. In situ hybridization was then used to analyze preprotachykinin-A (PPT-A) mRNA expression in the lesioned as well as in saline-injected control animals. The midbrain dopaminergic lesion caused a 22-25% increase in the level of PPT-A mRNA in cingulate cortex and frontoparietal cortex when analysed at 2 weeks of age, compared to saline-injected control animals. In contrast, the lesion caused no change in PPT-A mRNA expression in the neonatal caudate-putamen. These results indicate that dopamine neurons downregulate the expression of PPT-A mRNA specifically in cingulate cortex and frontoparietal cortex during early postnatal brain development. In the adult rat forebrain, lesioned at P3 and P6, no change in the level of PPT-A mRNA was seen in cingulate cortex and frontoparietal cortex. However, a 29% decrease in PPT-A mRNA was seen in the lateral caudate-putamen with no significant change in neurons of medial caudate-putamen. Thus, dopamine neurons appears to exert a region specific influence on PPT-A mRNA expression during brain development.
在出生后第3天和第6天，对用去甲肾上腺素摄取阻滞剂地昔帕明预处理过的动物进行脑室内注射6-羟基多巴胺，以产生多巴胺神经元的选择性损伤。然后，采用原位杂交技术分析损伤动物以及注射生理盐水的对照动物中前速激肽原A（PPT-A）mRNA的表达情况。与注射生理盐水的对照动物相比，在2周龄时分析发现，中脑多巴胺能损伤使扣带回皮质和额顶叶皮质中PPT-A mRNA水平增加了22% - 25%。相比之下，该损伤对新生尾状核-壳核中PPT-A mRNA的表达没有影响。这些结果表明，在出生后早期脑发育过程中，多巴胺神经元特异性地下调扣带回皮质和额顶叶皮质中PPT-A mRNA的表达。在成年大鼠前脑（在出生后第3天和第6天进行损伤）中，扣带回皮质和额顶叶皮质中PPT-A mRNA水平未见变化。然而，外侧尾状核-壳核中PPT-A mRNA下降了29%，而内侧尾状核-壳核的神经元中未见显著变化。因此，在脑发育过程中，多巴胺神经元似乎对PPT-A mRNA的表达发挥区域特异性影响。
