Matus-Leibovitch N, Nevo I, Vogel Z
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Brain Res Mol Brain Res. 1997 May;45(2):301-16. doi: 10.1016/s0169-328x(96)00265-3.
Quantitative reverse transcriptase-polymerase chain reaction and in situ hybridization techniques were used to determine the regional distribution of synapsin IIa and IIb mRNAs in rat central nervous system and to assess the effect of chronic morphine administration on the gene expression of these two isoforms of synapsin II. These isoforms are members of a family of neuron-specific phosphoproteins thought to be involved in the regulation of neurotransmitter release. Our data demonstrate the widespread distribution, yet regionally variable expression, of synapsin IIa and IIb mRNAs throughout the adult rat brain and spinal cord. The ratios of the relative abundance of synapsins IIa and IIb differed by up to 4.5-fold among the various regions studied. Synapsin IIa and IIb mRNAs were shown to be highly concentrated in the thalamus and in the hippocampus, whereas lower concentrations were found in most other central nervous system structures. In this study, we show differential regulation by morphine of synapsins IIa and IIb in various regions of the brain. In the striatum, a 2.4-fold increase was observed in the levels of synapsin IIa mRNA following chronic morphine regime, whereas no change was found for synapsin IIb. On the other hand, mRNA levels of synapsin IIb in spinal cord of chronically treated rats were markedly decreased (by 62%), while no alterations were observed in synapsin IIa. Selective regulation by morphine has also been demonstrated in several other central nervous system structures. The opiate-induced regulation of the gene expression of synapsin II isoforms could be viewed as one of the cellular adaptations to the persistent opiate effects and may be involved in the molecular mechanism underlying opiate tolerance and/or dependence.
采用定量逆转录聚合酶链反应和原位杂交技术,来确定大鼠中枢神经系统中突触素IIa和IIb mRNA的区域分布,并评估长期给予吗啡对突触素II这两种同工型基因表达的影响。这些同工型是神经元特异性磷蛋白家族的成员,被认为参与神经递质释放的调节。我们的数据表明,突触素IIa和IIb mRNA在成年大鼠的整个脑和脊髓中分布广泛,但区域表达存在差异。在所研究的不同区域中,突触素IIa和IIb相对丰度的比值相差高达4.5倍。突触素IIa和IIb mRNA在丘脑和海马中高度集中,而在大多数其他中枢神经系统结构中浓度较低。在本研究中,我们显示吗啡对脑不同区域的突触素IIa和IIb有不同的调节作用。在纹状体中,长期给予吗啡后,突触素IIa mRNA水平增加了2.4倍,而突触素IIb没有变化。另一方面,长期给药大鼠脊髓中突触素IIb的mRNA水平显著降低(降低了62%),而突触素IIa没有改变。在其他几个中枢神经系统结构中也证实了吗啡的选择性调节作用。阿片类药物对突触素II同工型基因表达的调节可被视为细胞对持续阿片类药物作用的适应性反应之一,可能参与了阿片类药物耐受性和/或依赖性的分子机制。