A TTX-sensitive local circuit is involved in the expression of PK2 and BDNF circadian rhythms in the mouse suprachiasmatic nucleus

A TTX-sensitive local circuit is involved in the expression of PK2 and BDNF circadian rhythms in the mouse suprachiasmatic nucleus
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DOI:
10.1111/j.1460-9568.2008.06053.x
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发表时间:
2008-02-01
影响因子:
3.4
通讯作者:
Honma, Ken-ichi
Honma, Ken-ichi
中科院分区:
医学3区
文献类型:
--
作者:
Baba, Kenkichi;Ono, Daisuke;Honma, Ken-ichi

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本研究探讨了成年小鼠视交叉上核(SCN)内局部电生理活动回路在昼夜节律表达中的作用。用Na+通道阻断剂河豚毒素(TTX)抑制培养SCN神经元的活性,并采用原位杂交技术检测13个基因在mRNA水平上的昼夜节律。SCN切片培养3天,在Per 1表达节律的高峰期应用TTX。应用TTX后,每隔4小时检查一次SCN切片,直至32小时。生物钟基因Per 1、Per 2、Bmal 1和Cry 1以及生物钟相关基因Dec 1、Dec 2、Rev-erb α、Rev-erb β和DBP表达的昼夜节律不受TTX处理的影响。与此相反,TTX完全取消了BDNF mRNA水平的昼夜节律,并大大降低了PK 2的节律。TTX对AVP mRNA表达的昼夜节律无明显影响。这些发现表明,通过Na+通道依赖性电生理活动的输入是不必要的时钟和时钟相关基因的昼夜节律的表达,但需要在SCN的BDNF和PK 2的昼夜节律的充分表达。河豚毒素敏感回路参与小鼠SCN中BDNF和PK 2昼夜节律的表达
The roles of a local circuit of electrophysiological activity were examined in the expression of circadian rhythms in the suprachiasmatic nucleus (SCN) of the adult mouse. The neuronal activity of cultured SCN was suppressed with tetrodotoxin (TTX), an Na+ channel blocker, and the circadian rhythms in mRNA level were assessed for 13 genes by in situ hybridization. SCN slices were cultured for 3 days and TTX was applied at the peak phase of Per1 expression rhythm. The SCN slices were examined at 4-h intervals up to 32 h after TTX application. The circadian rhythms in the expression of clock genes, Per1, Per2, Bmal1 and Cry1, and of clock-associated genes, Dec1, Dec2, Rev-erb alpha, Rev-erb beta and DBP, were not affected by TTX treatment. By contrast, TTX completely abolished the circadian rhythm in the BDNF mRNA level and substantially damped the rhythm in PK2. The circadian rhythm in the AVP mRNA level was not changed significantly by TTX. These findings indicate that input through Na+-channel-dependent electrophysiological activity is not necessary for the expression of the circadian rhythms of clock and clock-associated genes, but necessary for full expression of the circadian rhythms of BDNF and PK2 in the SCN. A TTX-sensitive circuit is involved in the expression of BDNF and PK2 circadian rhythms in the mouse SCN.