Boer G J, van Esseveldt L E, Rietveld W J
Netherlands Institute for Brain Research, Graduate School Neurosciences, Amsterdam, The Netherlands.
Chronobiol Int. 1998 Sep;15(5):551-66. doi: 10.3109/07420529808998707.
Fetal neurografts containing the suprachiasmatic nucleus (SCN) can restore the circadian locomotor and drinking rhythm of SCN-lesioned (SCNX) rat and hamster. This functional outcome finally proves that the endogenous biological clock autonomously resides in the SCN. Observations on the cellular requirements of the "new" SCN for restoration of the arrhythmic SCNX animals have led to some new insights and confirmed findings from other studies. A critical mass of SCN neurons appeared necessary for functional effects, whereas the temporal profile of reinstatement of rhythm correlated with the delayed maturation of the grafted SCN. Cytoarchitectonically, the grafted SCN does not seem to develop normally for all anatomical aspects. Complementary clusters of vasoactive intestinal polypeptide(VIP)- and vasopressin(VP)ergic neurons are formed, but somatostatin(SOM)ergic neurons do not always "join" this group, as is normally seen in situ. Nevertheless, these new SCNs can restore the ablated functions. As the period length of restored rhythms tends to vary, it might be that the grafted SCN underwent an altered or impaired maturation that resulted in a different setting of its clock mechanism. A prominent role of VIPergic neurons seems indicated by their presence in all functional grafts, but, although they may be required, these cells do not appear to be a sufficient condition for restoration of rhythm. Many grafts exhibit the presence of VIPergic cells without counteracting the arrhythmia, whereas VP- and SOMergic SCN neurons are usually present as well. Findings with VP-deficient Brattleboro rat grafts indicated that VP is not the primary obligatory signal of circadian activity. It is argued that perhaps the role of SOMergic neurons in the clock function of the (grafted) SCN has been insufficiently considered. However, one should keep in mind that the peptides of the various types of SCN neurons may function only as cofactors, mutually modulating molecular or bioelectrical cellular activities within the nucleus or the message of the main transmitter gamma-aminobutyric acid.
含有视交叉上核（SCN）的胎儿神经移植体能够恢复视交叉上核损伤（SCNX）大鼠和仓鼠的昼夜运动及饮水节律。这一功能结果最终证明内源性生物钟自主存在于视交叉上核中。对“新的”视交叉上核恢复无节律的SCNX动物所需细胞条件的观察带来了一些新见解，并证实了其他研究的发现。一定数量的视交叉上核神经元似乎是产生功能效应所必需的，而节律恢复的时间模式与移植的视交叉上核延迟成熟相关。从细胞结构上看，移植的视交叉上核在所有解剖学方面似乎都不能正常发育。形成了血管活性肠肽（VIP）能神经元和加压素（VP）能神经元的互补簇，但生长抑素（SOM）能神经元并不总是像在原位正常所见那样“加入”这个群体。然而，这些新的视交叉上核能恢复被切除的功能。由于恢复节律的周期长度往往会变化，可能是移植的视交叉上核经历了改变或受损的成熟过程，导致其时钟机制设置不同。VIP能神经元在所有功能性移植体中的存在似乎表明它们起着重要作用，但是，尽管它们可能是必需的，但这些细胞似乎并不是恢复节律的充分条件。许多移植体中存在VIP能细胞却没有抵消心律失常，而VP能和SOM能视交叉上核神经元通常也存在。对缺乏VP的布拉德福德大鼠移植体的研究结果表明，VP不是昼夜活动的主要必需信号。有人认为，也许SOM能神经元在（移植的）视交叉上核时钟功能中的作用尚未得到充分考虑。然而，应该记住各种类型视交叉上核神经元的肽可能仅作为辅助因子，相互调节核内分子或生物电细胞活动或主要递质γ-氨基丁酸的信息。
