Baba Kenkichi, Ono Daisuke, Honma Sato, Honma Ken-ichi
Department of Physiology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
Eur J Neurosci. 2008 Feb;27(4):909-16. doi: 10.1111/j.1460-9568.2008.06053.x. Epub 2008 Feb 13.
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-erbalpha, Rev-erbbeta 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.
研究了局部电生理活动回路在成年小鼠视交叉上核（SCN）昼夜节律表达中的作用。用钠通道阻滞剂河豚毒素（TTX）抑制培养的SCN神经元活动，并通过原位杂交评估13个基因的mRNA水平昼夜节律。将SCN切片培养3天，并在Per1表达节律的峰值期施加TTX。在施加TTX后32小时内，每隔4小时检查一次SCN切片。时钟基因Per1、Per2、Bmal1和Cry1以及时钟相关基因Dec1、Dec2、Rev-erbalpha、Rev-erbbeta和DBP的表达昼夜节律不受TTX处理的影响。相比之下，TTX完全消除了BDNF mRNA水平的昼夜节律，并显著减弱了PK2的节律。TTX对AVP mRNA水平的昼夜节律没有显著影响。这些发现表明，通过钠通道依赖性电生理活动的输入对于时钟和时钟相关基因的昼夜节律表达不是必需的，但对于SCN中BDNF和PK2昼夜节律的充分表达是必需的。一个对TTX敏感的回路参与了小鼠SCN中BDNF和PK2昼夜节律的表达。
