Kopp N, Najimi M, Champier J, Chigr F, Charnay Y, Epelbaum J, Jordan D
Laboratoire d'Anatomie Pathologique, Faculté de Médecine Alexis Carrel, Lyon, France.
Prog Brain Res. 1992;93:167-87; discussion 187-8. doi: 10.1016/s0079-6123(08)64571-9.
The brains of mammals are not mature at birth, in particular in humans. Growth and brain development are influenced by the hormonal state in which the hypothalamus plays the major regulatory role. The maturation of the hormonal patterns leads to the physiological establishment of chronological variations as revealed by the circadian variations of both hypothalamic peptides and pituitary hormones (as illustrated for hypothalamic-pituitary-thyroid axis by the determination of thyro-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) circadian rhythms in the rat (Jordan et al., 1989)). It has been established that hypothalamic peptide variations are regulated by hormonal feed-back and amine systems, with the maturation of the latter also being dependent upon the whole functional maturation of the brain. Though these systems have been studied in the rat, very little information is currently available with regard to the human brain. The only biochemical or immunohistochemical information published to date concerns either the fetus or the adult. We have studied four main peptidergic systems (somatostatin-releasing inhibiting factor (SRIF), thyrotropin-releasing hormone (TRH), luteinizing hormone-releasing hormone (LHRH) and delta sleep inducing peptide (DSIP) in post-mortem adults and infants and in sudden infant death syndrome (SIDS) brains either by autoradiography and/or immunochemistry of radioimmunology. From a technical point of view, human brain studies display certain pitfalls not present in animal studies. These may be divided into two subclasses: ante- and post-mortem. Ante-mortem problems concern mainly sex, laterality, nutritional and treatment patterns while post-mortem problems concern post-mortem delay and conditions before autopsy and hypothalamic dissection. This might induce dramatic changes in morphological, immunochemical and autoradiographic evaluations. The matching of pathological subjects with controls is particularly difficult in the case of SIDS because of the rapid changes which take place in physiological regulatory processes during the first year of life. Thus, the treatment of hypothalamic tissue samples both for immunochemistry, radioimmunology and autoradiographic studies required techniques which must be rigorously controlled. For example, SRIF studies were carried out with three different antibodies, which gave similar results. The use of different technical procedures as well as different antibodies is discussed. These types of differences might explain, at least in part, the discrepancy observed until now. As previously described in the fetus (Bugnon et al., 1977b; Bouras et al., 1987), we confirmed that in the infant hypothalamic SRIF immunoreactive cell bodies are present in the paraventricular and suprachiasmatic nuclei and in the periventricular area.(ABSTRACT TRUNCATED AT 400 WORDS)
哺乳动物的大脑在出生时并不成熟,人类尤其如此。生长和大脑发育受到激素状态的影响,其中下丘脑起着主要的调节作用。激素模式的成熟导致了时间变化的生理确立,如下丘脑肽和垂体激素的昼夜节律所示(以大鼠下丘脑 - 垂体 - 甲状腺轴为例,通过测定促甲状腺激素(TSH)和促甲状腺激素释放激素(TRH)的昼夜节律来说明(乔丹等人,1989年))。已经确定,下丘脑肽的变化受激素反馈和胺系统的调节,而后者的成熟也依赖于大脑的整体功能成熟。尽管这些系统已在大鼠中进行了研究,但目前关于人类大脑的信息非常少。迄今为止发表的唯一生化或免疫组化信息涉及胎儿或成人。我们通过放射自显影和/或放射免疫学的免疫化学研究了死后成人、婴儿以及婴儿猝死综合征(SIDS)大脑中的四种主要肽能系统(生长抑素释放抑制因子(SRIF)、促甲状腺激素释放激素(TRH)、促黄体生成素释放激素(LHRH)和δ睡眠诱导肽(DSIP))。从技术角度来看,人类大脑研究存在一些动物研究中不存在的陷阱。这些陷阱可分为两类:生前和死后。生前问题主要涉及性别、偏侧性、营养和治疗模式,而死后问题涉及死后延迟以及尸检和下丘脑解剖前的状况。这可能会在形态学、免疫化学和放射自显影评估中引起巨大变化。在SIDS病例中,由于生命第一年生理调节过程中发生的快速变化,将病理受试者与对照组进行匹配特别困难。因此,用于免疫化学、放射免疫学和放射自显影研究的下丘脑组织样本处理需要严格控制的技术。例如,使用三种不同的抗体进行SRIF研究,结果相似。文中讨论了不同技术程序以及不同抗体的使用情况。这些类型的差异可能至少部分解释了迄今为止观察到的差异。如先前在胎儿中所描述的(比尼翁等人,1977b;布拉斯等人,1987),我们证实婴儿下丘脑中的SRIF免疫反应性细胞体存在于室旁核、视交叉上核和室周区域。(摘要截取自400字)