缰核在视交叉上核—松果体昼夜节律控制系统中的作用研究

发布时间：2018-09-04 05:58

【摘要】： 昼夜节律是生物的基本生命特征之一,它的稳定是机体正常生理功能进行的基础。许多资料证明:外界光照可通过下丘脑视交叉上核(SCN)和松果体(PG)来调节昼夜节律,并使内源性昼夜节律和环境的24小时昼夜节律同步,提示SCN和PG在机体昼夜节律的调节中起重要作用,缰核(Hb)密切联系这两个结构,并且Hb本身也有视网膜纤维投射,因此,Hb可能介导SCN—PG昼夜节律的信息传递,与SCN和PG等结构共同组成中枢昼夜节律控制系统。本实验首先应用电生理学方法,观察电刺激或化学刺激兴奋SCN及化学阻断SCN,对外侧缰核(LHb)和内侧缰核(MHb)神经元自发放电的影响,从细胞水平弄清SCN与Hb间的功能联系。进一步应用逆转录聚合酶链法(RT-PCR),在海人酸(KA)损毁LHb2周后,检测SCN和PG在六个不同时间点的时钟基因Per2、Bmal1和Clock mRNA的表达水平,以及褪黑素(MT)合成限速酶N-乙酰转移酶(NAT)及其受体MT1和MT2 mRNA的表达水平。探讨SCN和PG的昼夜节律相关基因和物质的表达是否需要有Hb的存在,从另一角度明确Hb的作用。实验结果显示:50%Hb神经元对SCN刺激有反应,且不同部位的Hb神经元对SCN刺激的电生理反应不同,即MHb主要表现为抑制,而LHb则没有明显趋势,但SCN被阻断后对LHb起抑制效应;LHb损毁后PG和SCN内NAT以及MT1、MT2 mRNA在不同时间点的表达多下调,但其表达的周期没有改变;SCN和PG中时钟基因Per2、Bmal1和Clock的昼夜表达水平,在损毁组也多显著下降,但其周期也无变化。以上结果提示LHb与SCN和PG之间具有密切的功能联系,LHb可通过影响PG活动进而影响SCN的功能,同时LHb也接受SCN和PG的调控。LHb可能通过影响PG内褪黑素的合成及其受体的表达,进而影响时钟基因的表达,参与中枢昼夜节律调节,成为中枢昼夜节律调控系统组构中的重要成分。
[Abstract]:Circadian rhythm is one of the basic biological characteristics, and its stability is the basis of normal physiological function. Many data have shown that the circadian rhythm can be regulated by (SCN) and (PG) in the supraoptic nucleus of hypothalamus, and the circadian rhythm of the endogenous circadian rhythm is synchronized with the circadian rhythm of the environment in 24 hours. It is suggested that SCN and PG play an important role in the regulation of circadian rhythm. Habenula (Hb) is closely related to these two structures, and Hb itself also has retinal fiber projection. Therefore, Hb may mediate the transmission of SCN-PG circadian rhythm. The central circadian rhythm control system is composed of SCN and PG. In this study, we first observed the effects of electrical or chemical stimulation on the spontaneous discharges of (LHb) and (MHb) neurons in the lateral habenular nucleus and the medial habenular nucleus by electrical or chemical stimulation of excited SCN and chemically blocked SCN, and clarified the functional relationship between SCN and Hb at the cellular level. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of clock genes Per2,Bmal1 and Clock mRNA in SCN and PG at six different time points after kainic acid (KA) destroyed LHb2 week. And the expression level of melatonin (MT) synthesis rate-limiting enzyme N-acetyltransferase (NAT) and its receptors MT1 and MT2 mRNA. To investigate whether the presence of Hb is necessary for the expression of circadian rhythm related genes and substances of SCN and PG, and to clarify the role of Hb from another perspective. The results showed that the HB neurons in the ratio of 50 to 50 had a response to SCN stimulation, and the electrophysiological responses of Hb neurons in different parts to SCN stimulation were different. That is, MHb was mainly inhibited, but LHb had no obvious tendency. The expression of NAT and MT1,MT2 mRNA in PG and SCN were down-regulated at different time points, but the expression cycle of NAT and Clock in PG and PG did not change the circadian expression level of clock genes Per2,Bmal1 and Clock in PG and PG. It also decreased significantly in the lesion group, but its cycle did not change. These results suggest that there is a close functional relationship between LHb and SCN and PG. LHb may affect the function of SCN by affecting the activity of PG, and LHb also accepts the regulation of SCN and PG. LHb may affect the synthesis of melatonin and the expression of its receptors in PG. Furthermore, the expression of clock gene is affected, and it participates in the regulation of central circadian rhythm and becomes an important component in the system of central circadian rhythm regulation.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R33

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