Suprachiasmatic function in a circadian period mutant: Duper alters light-induced activation of vasoactive intestinal peptide cells and PERIOD1 immunostaining

Suprachiasmatic function in a circadian period mutant: Duper alters light-induced activation of vasoactive intestinal peptide cells and PERIOD1 immunostaining
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DOI:
10.1111/ejn.14214
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发表时间:
2018-12-01
影响因子:
3.4
通讯作者:
Bittman, Eric L.
Bittman, Eric L.
中科院分区:
医学3区
文献类型:
--
作者:
Manoogian, Emily N. C.;Kumar, Ajay;Bittman, Eric L.

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哺乳动物的昼夜节律是由光刺激引起的,这些光刺激通过视网膜投射传递到视交叉上核(SCN)的核心。神经元激活,表现为即刻早期基因c-fos的表达,导致核心时钟基因per 1的转录。仓鼠中的duper突变缩短了昼夜节律周期并放大了光诱导的相移。我们进行了两个实验,以比较c-FOS免疫反应(IR)和PER 1-IR细胞的数量,染色的强度,在SCN的野生型(WT)和duper仓鼠在不同的时间间隔后,介绍了15分钟的光脉冲在主观的早期夜晚。光诱导c-FOS-ir在1小时内在duper的背尾侧SCN中,但不是WT仓鼠。在表达血管活性肠肽(VIP)的细胞中,光诱导的c-FOS-IR在Duper中比WT仓鼠更大,VIP在SCN细胞振荡器的同步中起着关键作用。在光脉冲后,PER 1-IR细胞被发现在SCN比FOS-IR更内侧的部分,并出现了更长的潜伏期和更长的时间过程中,在VIP细胞的duper比野生型仓鼠。我们的研究结果表明,duper等位基因改变SCN功能的方式,可能有助于自由运行期和相位重置的变化。
Mammalian circadian rhythms are entrained by photic stimuli that are relayed by retinal projections to the core of the suprachiasmatic nucleus (SCN). Neuronal activation, as demonstrated by expression of the immediate early gene c-fos, leads to transcription of the core clock gene per1. The duper mutation in hamsters shortens circadian period and amplifies light-induced phase shifts. We performed two experiments to compare the number of c-FOS immunoreactive (ir) and PER1-ir cells, and the intensity of staining, in the SCN of wild-type (WT) and duper hamsters at various intervals after presentation of a 15-min light pulse in the early subjective night. Light-induced c-FOS-ir within 1 hr in the dorsocaudal SCN of duper, but not WT hamsters. In cells that express vasoactive intestinal peptide (VIP), which plays a critical role in synchronization of SCN cellular oscillators, light-induced c-FOS-ir was greater in duper than WT hamsters. After the light pulse, PER1-ir cells were found in more medial portions of the SCN than FOS-ir, and appeared with a longer latency and over a longer time course, in VIP cells of duper than wild-type hamsters. Our results indicate that the duper allele alters SCN function in ways that may contribute to changes in free running period and phase resetting.