Bernardis L L, Bellinger L L
VA Western New York Healthcare System, State University of New York at Buffalo 14215, USA.
Proc Soc Exp Biol Med. 1998 Sep;218(4):284-306. doi: 10.3181/00379727-218-44296.
This article reviews data that have accumulated since the early 1970s on the role of the dorsomedial hypothalamic nucleus (DMN) in neuroendocrine and autonomic homeostasis. Both the ventromedial hypothalamic nucleus (VMN) and the lateral hypothalamic area (LHA) project to the DMN, which in turn projects to the paraventricular nucleus of the hypothalamus (PVN), thus placing the DMN at an important nodal point of neuroendocrine/autonomic circuitries. The DMN is composed of cells and fibers containing neuropeptide Y (NPY), and the nutritional status (starvation-refeeding) is reflected in NPY levels of both VMN and DMN in Sprague-Dawley, Zucker (fa/fa), and corpulent rats (cp/cp JCR:LA). The DMN is involved in the final common pathway of corticotrophin-releasing hormone (CRH) secretion by the PVN, sympathetic nervous system outflow to the adrenal gland, and brown adipose tissue (BAT) thermogenesis. The DMN is also part of a "fear circuitry" regulating cardiovascular responses to stress such as myocardial blood flow and the tachycardia associated with the defense reaction. This appears to be mediated by a gamma amino butyric acid (GABA) mechanism. Although exhibiting reduced ponderal and linear growth and hypophagia and hypodipsia, the rat with DMN lesions (DMNL rat) has normal body composition, anabolic hormone levels, and intermediary metabolism, and it responds normally to numerous endocrine, nutritional, intra- and extracellular thirst and body weight-regulatory challenges. The DMNL rat shows normal efficiency of food utilization, but shows an attenuated response to the feeding-stimulatory effect of insulin. The only other lesion-induced abnormalities are hyperprolactinemia and a disrupted circadian corticosterone rhythm. The hyperprolactinemia in DMNL rats appears to be related to an attenuation of dopamine (DA). Rats with DMNL are capable of mating and can bear offspring, but there is a dramatic effect on litter size and other litter parameters that only improves when one parent is a DMNL rat. Antiaging effects produced by DMNL are evident in the prevention of age-associated microalbuminuria and kidney lesions, as well as, in prevention of the age-related decline in circulating insulin-like growth factor I (IGF-I). Recent evidence suggests that DMN, together with the VMN and the arcuate nucleus (ARC) of the hypothalamus, may be part of the circuitry that is responsive to the feedback signal from adipose tissue by the hormone leptin. The above findings and others suggest that the DMN plays a diverse role in physiological regulatory processes.
本文综述了自20世纪70年代初以来积累的有关下丘脑背内侧核(DMN)在神经内分泌和自主稳态中作用的数据。腹内侧下丘脑核(VMN)和外侧下丘脑区(LHA)均投射至DMN,而DMN又投射至下丘脑室旁核(PVN),从而使DMN处于神经内分泌/自主神经回路的重要节点位置。DMN由含有神经肽Y(NPY)的细胞和纤维组成,在斯普拉格-道利大鼠、 Zucker(fa/fa)大鼠和肥胖大鼠(cp/cp JCR:LA)中,VMN和DMN的NPY水平反映了营养状况(饥饿-再喂养)。DMN参与了PVN分泌促肾上腺皮质激素释放激素(CRH)的最终共同途径、交感神经系统向肾上腺的输出以及棕色脂肪组织(BAT)的产热过程。DMN也是调节对压力的心血管反应(如心肌血流量和与防御反应相关的心动过速)的“恐惧回路”的一部分。这似乎是由γ-氨基丁酸(GABA)机制介导的。虽然患有DMN损伤的大鼠(DMNL大鼠)体重和线性生长减少,摄食和饮水减少,但其身体组成、合成代谢激素水平和中间代谢正常,并且对多种内分泌、营养、细胞内和细胞外口渴及体重调节挑战有正常反应。DMNL大鼠食物利用效率正常,但对胰岛素的促进食刺激作用反应减弱。唯一其他由损伤引起的异常是高催乳素血症和昼夜皮质酮节律紊乱。DMNL大鼠的高催乳素血症似乎与多巴胺(DA)的减少有关。患有DMNL的大鼠能够交配并能生育后代,但对窝仔大小和其他窝仔参数有显著影响,只有当一方亲本是DMNL大鼠时情况才会有所改善。DMNL产生的抗衰老作用在预防与年龄相关的微量白蛋白尿和肾脏病变以及预防循环胰岛素样生长因子I(IGF-I)的年龄相关下降方面很明显。最近的证据表明,DMN与VMN和下丘脑弓状核(ARC)一起,可能是对激素瘦素来自脂肪组织的反馈信号作出反应的回路的一部分。上述发现及其他研究表明,DMN在生理调节过程中发挥着多种作用。