Velísková J, Kubová H, Friedman L K, Wu R, Sperber E F, Zukin R S, Moshé S L
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Ital J Neurol Sci. 1998 Aug;19(4):205-10. doi: 10.1007/BF02427602.
The substantia nigra pars reticulata (SNR) controls the spread of seizures. GABA(A)ergic drug (agonist or antagonist) infusions into the SNR have age-specific and site-specific effects on flurothyl-induced seizures. Developmental and cell-specific regulation of GABA(A) receptor subunit expression may be responsible for these specific effects. To test this hypothesis, in situ hybridization was used to examine regional expression of alpha1 and gamma2L GABA(A) receptor subunit mRNAs in the SNR during development. Distinct temporal and spatial patterns of expression were observed. In rats at postnatal days (PN) 21-60, fewer neurons were labeled with probes directed to alpha1 and gamma2L subunits in SNRanterior compared with SNRposterior. In addition, neurons in SNRanterior contained higher amounts of hybridization grains than in SNRposterior. In PN 15 rats, the labeling of neurons was relatively diffuse throughout the anterior and posterior SNR regions with moderate amounts of hybridization grains for both subunits. The finding of age-related differential distribution of alpha1 and gamma2L subunit mRNAs in the SNR suggests that GABA(A) receptor heterogeneity may play a role in the age-specific and site-specific effects of GABA(A)ergic agents on seizures in the SNR.
黑质网状部(SNR)控制癫痫发作的扩散。向SNR内注入GABA(A)能药物(激动剂或拮抗剂)对氟烷诱导的癫痫发作具有年龄特异性和部位特异性影响。GABA(A)受体亚基表达的发育和细胞特异性调节可能是这些特异性影响的原因。为了验证这一假设,采用原位杂交技术检测发育过程中SNR内α1和γ2L GABA(A)受体亚基mRNA的区域表达。观察到了不同的时空表达模式。在出生后第(PN)21 - 60天的大鼠中,与SNR后部相比,针对α1和γ2L亚基的探针标记的SNR前部神经元较少。此外,SNR前部的神经元比SNR后部含有更多的杂交颗粒。在PN 15大鼠中,神经元的标记在整个SNR前部和后部区域相对弥散,两个亚基的杂交颗粒数量适中。SNR中α1和γ2L亚基mRNA与年龄相关的差异分布这一发现表明,GABA(A)受体的异质性可能在GABA(A)能药物对SNR癫痫发作影响的年龄特异性和部位特异性中起作用。