Stress upregulates TPH1 but not TPH2 mRNA in the rat dorsal raphe nucleus:: Identification of two TPH2 mRNA splice variants
Stress upregulates TPH1 but not TPH2 mRNA in the rat dorsal raphe nucleus:: Identification of two TPH2 mRNA splice variants
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DOI：
10.1007/s10571-007-9259-5
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发表时间：
2008-05-01
影响因子：
4
通讯作者：
Fluegge, Gabriele
中科院分区：
文献类型：
--
作者：
Abumaria, Nashat;Ribic, Adema;Fluegge, Gabriele
血清素与压力相关的精神病理学有关。已知5-羟色胺生物合成的限速酶色氨酸羟化酶的两种同种型，TPH 1和TPH 2。我们在这里表明，在大鼠中缝背核（DRN），在大脑中的5-HT神经元的数量最多的核，TPH 1 mRNA的表达水平较低，但可通过实时定量PCR和原位杂交检测，而在松果体（PiG），TPH 1 mRNA的强烈表达。为了研究应激对TPH表达的影响，我们将雄性Wistar大鼠暴露于每日束缚应激1周。如定量实时PCR所示，TPH 1 mRNA在DRN中被应激上调2.5倍，但在PiG中没有。使用3 '-RACE，我们在大鼠DRN中鉴定了两种TPH 2 mRNA剪接变体，它们的3'-非翻译区（UTR）长度不同。TPH 2b（具有短的3 '-UTR）是DRN中的主要变体，而TPH 2a（具有较长的3'-UTR）在该核中显示低丰度。在PiG中，仅TPH 2b是可检测的，揭示了低水平的表达。两种TPH 2剪接变体的表达不受应激的影响，无论是在DRN还是在PiG中。这些数据表明，TPH 1在DRN的多巴胺能神经元可能是相关的应激诱导的精神病理学。
Serotonin is implicated in stress-related psychopathologies. Two isoforms of the rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase, TPH1 and TPH2, are known. We show here that in the rat dorsal raphe nucleus (DRN), the nucleus that contains the highest number of 5-HT neurons in the brain, TPH1 mRNA reveals a low level of expression but is detectable both by quantitative real-time PCR and in situ hybridization whereas in the pineal gland (PiG), TPH1 mRNA is strongly expressed. To examine effects of stress on TPH expression we exposed male Wistar rats to daily restraint stress for 1 week. As shown by quantitative real-time PCR, TPH1 mRNA is 2.5-fold upregulated by the stress in DRN but not in PiG. Using 3'-RACE, we identified two TPH2 mRNA splice variants in the rat DRN which differ in the length of their 3'-untranslated regions (UTRs). TPH2b (with a short 3'-UTR) is the predominant variant in the DRN, whereas TPH2a (with a longer 3'-UTR) shows a low abundance in this nucleus. In the PiG, only TPH2b is detectable revealing a low level of expression. Expression of both TPH2 splice variants is not affected by stress, neither in DRN nor in the PiG. These data indicate that TPH1 in the serotonergic neurons of the DRN might be relevant for stress-induced psychopathologies.