Chen J F, Weiss B
Department of Pharmacology, Medical College of Pennsylvania/EPPI, Philadelphia 19129.
Brain Res Dev Brain Res. 1991 Nov 19;63(1-2):95-104. doi: 10.1016/0165-3806(91)90070-y.
The ontogenetic expression of the D2 dopamine receptor (D2R) mRNA has been characterized in rat corpus striatum by in situ hybridization histochemistry and Northern and slot blot analyses using oligonucleotide probes directed toward either the D2R-A subtype of the D2R mRNA or to both the D2R-A and D2R-B subtypes of the D2R mRNA. The results showed that both D2R mRNAs were detected in rat striatum at birth, gradually increased until day 16 postnatally (P16), then declined slightly. At early stages of development, the hybridization signal, when viewed under low magnification, was fairly evenly distributed throughout the striatum. However, later in development (P16) a cluster pattern became manifest. Autoradiographic studies using the mu-opiate receptor as an indication of striatal 'patches' in serial, adjacent sections of striatum indicated that the cluster pattern of the D2R mRNA was not associated solely with the patch or matrix compartments of the striatum. A cellular analysis showed that at early developmental stages the quantity of D2R mRNA per cell was very low in striatum. During the first two postnatal weeks, certain subpopulations of striatal neurons evidenced a marked increase in the expression of D2R mRNA per cell. Administration of 6-hydroxydopamine into neonatal rats failed to significantly change the developmental profile of D2R mRNA in the rat striatum of 16- and 32-day-old animals, although the same treatment caused a marked increase in proenkephalin mRNA. These results suggest that the postnatal development of the D2R mRNA in rat striatum correlates well with the ontogeny of the D2 dopamine receptor, that the developmental expression of the D2R mRNA is highly associated with the maturation and differentiation of striatal neurons, and that the development of the D2R mRNA in rat striatum, unlike that of proenkephalin mRNA, can proceed even with reduced dopaminergic afferent input from the substantia nigra.
通过原位杂交组织化学以及使用针对D2R mRNA的D2R - A亚型或D2R mRNA的D2R - A和D2R - B亚型的寡核苷酸探针进行的Northern印迹和狭缝印迹分析,对大鼠纹状体中D2多巴胺受体(D2R)mRNA的个体发生表达进行了表征。结果显示,两种D2R mRNA在出生时的大鼠纹状体中均可检测到,在出生后第16天(P16)之前逐渐增加,然后略有下降。在发育早期,低倍镜下观察到的杂交信号在整个纹状体中分布相当均匀。然而,在发育后期(P16),出现了簇状模式。使用μ - 阿片受体作为纹状体连续相邻切片中纹状体“斑块”指标的放射自显影研究表明,D2R mRNA的簇状模式并非仅与纹状体的斑块或基质区室相关。细胞分析表明,在发育早期,纹状体中每个细胞的D2R mRNA数量非常低。在出生后的前两周,纹状体神经元的某些亚群显示每个细胞的D2R mRNA表达显著增加。向新生大鼠注射6 - 羟基多巴胺未能显著改变16日龄和32日龄动物大鼠纹状体中D2R mRNA的发育模式,尽管相同处理导致前脑啡肽原mRNA显著增加。这些结果表明,大鼠纹状体中D2R mRNA的出生后发育与D2多巴胺受体的个体发生密切相关,D2R mRNA的发育表达与纹状体神经元的成熟和分化高度相关,并且大鼠纹状体中D2R mRNA的发育与前脑啡肽原mRNA不同,即使来自黑质的多巴胺能传入输入减少也能进行。