The University of British Columbia, Vancouver, BC, Canada, V6T 1Z3.
J Mol Neurosci. 2012 Nov;48(3):696-705. doi: 10.1007/s12031-011-9678-0. Epub 2011 Nov 25.
Somatostatin (SST)-positive medium-sized aspiny interneurons are selectively spared in excitotoxicity. The biological effects of SST are mediated via five different receptors, namely somatostatin receptor (SSTR)1-5; however, SSTR subtype spared in excitotoxicity and involved in neuroprotection is not known. Dopamine- and cAMP-regulated phosphoprotein (DARPP-32) is predominantly expressed in medium-sized projection neurons that are most vulnerable in excitotoxicity. In the present study, we determined the colocalization of SST and SSTRs with DARPP-32 in rat brain cortical and striatal regions using immunofluorescence immunohistochemistry. We also determined the expression of DARPP-32 in SSTR1-5 immunoprecipitate prepared from cortex and striatum. SST-positive neurons in cortex and striatum are devoid of colocalization with DARPP-32. However, in cortical and striatal brain regions, three different neuronal populations either expressing SSTRs and DARPP-32 alone or displaying colocalization were identified. Quantitative analysis reveals that in cortex and striatum, SSTR1 and 5 are most predominant receptor subtypes colocalized with DARPP-32 followed by SSTR4, 2, and 3 in cortex whereas SSTR2, 4, and 3 in striatum. Importantly, DARPP-32 is expressed in SSTR1-5 immunoprecipitate prepared from cortex and striatum. Taken together, these results provide the first evidence that the SSTR-positive neurons lacking colocalization with DARPP-32 might be spared in excitotoxicity.
生长抑素（SST）阳性中型无刺中间神经元在兴奋毒性中被选择性保留。SST 的生物学效应通过五种不同的受体介导，即生长抑素受体（SSTR）1-5；然而，在兴奋毒性中被保留并参与神经保护的 SSTR 亚型尚不清楚。多巴胺和 cAMP 调节的磷蛋白（DARPP-32）主要表达在中型投射神经元中，这些神经元在兴奋毒性中最易受到影响。在本研究中，我们使用免疫荧光组织化学法确定了大鼠大脑皮质和纹状体区域中 SST 和 SSTRs 与 DARPP-32 的共定位。我们还确定了 DARPP-32 在从皮质和纹状体制备的 SSTR1-5 免疫沉淀物中的表达。皮质和纹状体中的 SST 阳性神经元缺乏与 DARPP-32 的共定位。然而，在皮质和纹状体脑区中，鉴定出三种不同的神经元群体，它们单独表达 SSTRs 和 DARPP-32 或显示共定位。定量分析表明，在皮质和纹状体中，SSTR1 和 5 是与 DARPP-32 共定位的最主要的受体亚型，其次是 SSTR4、2 和 3 在皮质中，而 SSTR2、4 和 3 在纹状体中。重要的是，DARPP-32 表达在从皮质和纹状体制备的 SSTR1-5 免疫沉淀物中。总之，这些结果提供了第一个证据，表明缺乏与 DARPP-32 共定位的 SSTR 阳性神经元可能在兴奋毒性中被保留。
