Light-induced phase shift in the Syrian hamster (Mesocricetus auratus) is attenuated by the PACAP receptor antagonist PACAP6-38 or PACAP immunoneutralization

Light-induced phase shift in the Syrian hamster (Mesocricetus auratus) is attenuated by the PACAP receptor antagonist PACAP6-38 or PACAP immunoneutralization
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DOI:
10.1046/j.1460-9568.2003.03000.x
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发表时间:
2003-11-01
影响因子:
3.4
通讯作者:
Fahrenkrug, J
Fahrenkrug, J
中科院分区:
医学3区
文献类型:
--
作者:
Bergström, AL;Hannibal, J;Fahrenkrug, J

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视交叉上核(SCN)产生的昼夜节律每天通过视网膜下丘脑束(RHT)由光调节(携带)。RHT包含两种神经递质,谷氨酸和垂体腺苷酸环化酶激活多肽(PACAP),据信它们介导光对生物钟的相移效应。在本研究中,我们阐明了PACAP在光诱导的仓鼠夜间早期相移中的作用,并表明:(i)特定的PAC 1受体拮抗剂显著减弱了光诱导的转轮活动的相位延迟(PACAP 6 -38)或通过在光刺激前脑室内注射特异性抗PACAP抗体进行免疫阻断;(二)PACAP管理接近SCN能够相位延迟的昼夜节律的转轮活动以类似的方式光;(三)PACAP是本仓鼠RHT,共定位与黑视蛋白,最近确定的视蛋白,已被认为是一种昼夜节律的色素。研究结果表明,PACAP是一种神经递质的RHT介导的光信息的时钟,可能通过黑视蛋白位于专门的PACAP表达细胞的RHT。
Circadian rhythms generated by the suprachiasmatic nucleus (SCN) are daily adjusted (entrained) by light via the retinohypothalamic tract (RHT). The RHT contains two neurotransmitters, glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP), which are believed to mediate the phase-shifting effects of light on the clock. In the present study we have elucidated the role of PACAP in light-induced phase shifting at early night in hamsters and shown that (i) light-induced phase delay of running-wheel activity was significantly attenuated by a specific PAC1 receptor antagonist (PACAP6-38) or by immunoblockade with a specific anti-PACAP antibody injected intracerebroventricularly before light stimulation; (ii) PACAP administered close to the SCN was able to phase-delay the circadian rhythm of running-wheel activity in a similar way to light; (iii) PACAP was present in the hamster RHT, colocalized with melanopsin, a recently identified opsin which has been suggested to be a circadian photopigment. The findings indicate that PACAP is a neurotransmitter of the RHT mediating photic information to the clock, possibly via melanopsin located exclusively on the PACAP-expressing cells of the RHT.