Robust and tissue-specific expression of TPH2 versus TPH1 in rat raphe and pineal gland
Robust and tissue-specific expression of TPH2 versus TPH1 in rat raphe and pineal gland
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DOI：
10.1016/j.biopsych.2003.09.002
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发表时间：
2004-02-15
影响因子：
10.6
通讯作者：
Burke, S
中科院分区：
文献类型：
--
作者：
Patel, PD;Pontrello, C;Burke, S
背景：中缝核神经元能细胞的调节是重性抑郁症病理生理学流行假说的基础。色氨酸羟化酶（TPH）是5-羟色胺生物合成的限速酶，但脑干TPH mRNA的表达一直难以测量和研究。方法：采用原位杂交组织化学方法，对Sprague-Dawley大鼠脑组织中TPH 1和TPH 2 mRNA进行了研究。半定量技术被用来估计相对mRNA水平在个别cells.Results：几乎完全，TPH 2 mRNA表达中缝，在重叠的组织学定义的中缝核的模式。与此形成鲜明对比的是，TPH 1（先前已知的TPH）主要在松果体中表达。在这些旁系同源物的表达中没有明显的重叠。TPH 2 mRNA在单个中缝细胞中的表达水平比TPH 1在松果体cytos.Conclusions中的表达水平高约2.5倍：TPH 2 mRNA具有与脑干中缝核一致的解剖表达模式，并且可能是引起这些细胞中大部分TPH活性的基因。TPH 2在脑干中的稳定表达有助于中缝5-羟色胺生物合成的转录调控研究。
Background: Regulation of raphe serotonergic cells is fundamental to the prevailing hypothesis of major depression pathophysiology. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin biosynthesis, but brainstem TPH mRNA expression has been difficult to measure and study. Recently, a novel paralog of TPH, TPH2 (or neuronal TPH), was described, but its anatomic expression is unknown.Methods: In situ hybridization histochemical survey was conducted across Sprague-Dawley rat brain for TPH1 and TPH2 mRNA. Semiquantitative techniques were used to estimate relative mRNA levels in individual cells.Results: Almost exclusively, TPH2 mRNA is expressed in raphe, in a pattern overlapping the histologically defined raphe nuclei. In sharp contrast, TPH1 (the previously known TPH) is expressed predominantly in pineal gland. There is no appreciable overlap in the expression of these paralogs. The level of TPH2 mRNA expression in individual raphe cells is approximately 2.5-fold greater than the level of TPH1 expression in pinealocytes.Conclusions: TPH2 mRNA has an anatomic expression pattern consistent with brainstem raphe nuclei and is likely to be the gene giving rise to the majority of TPH activity in these cells. The robust expression of TPH2 in brainstem should facilitate studies on the transcriptional regulation of raphe serotonin biosynthesis.