Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin.
Am J Physiol Endocrinol Metab. 2013 Dec;305(12):E1452-63. doi: 10.1152/ajpendo.00293.2013. Epub 2013 Oct 22.
Numerous studies have demonstrated that both the hypothalamic paraventricular nuclei (PVN) and ventromedial nuclei (VMN) regulate energy homeostasis through behavioral and metabolic mechanisms. Receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) are abundantly expressed in these nuclei, suggesting PACAP may be critical for the regulation of feeding behavior and body weight. To characterize the unique behavioral and physiological responses attributed to select hypothalamic cell groups, PACAP was site-specifically injected into the PVN or VMN. Overall food intake was significantly reduced by PACAP at both sites; however, meal pattern analysis revealed that only injections into the PVN produced significant reductions in meal size, duration, and total time spent eating. PACAP-mediated hypophagia in both the PVN and VMN was abolished by PAC1R antagonism, whereas pretreatment with a VPACR antagonist had no effect. PACAP injections into the VMN produced unique changes in metabolic parameters, including significant increases in core body temperature and spontaneous locomotor activity that was PAC1R dependent whereas, PVN injections of PACAP had no effect. Finally, PACAP-containing afferents were identified using the neuronal tracer cholera toxin subunit B (CTB) injected unilaterally into the PVN or VMN. CTB signal from PVN injections was colocalized with PACAP mRNA in the medial anterior bed nucleus of the stria terminalis, VMN, and lateral parabrachial nucleus (LPB), whereas CTB signal from VMN injections was highly colocalized with PACAP mRNA in the medial amygdala and LPB. These brain regions are known to influence energy homeostasis perhaps, in part, through PACAP projections to the PVN and VMN.
大量研究表明，下丘脑室旁核 (PVN) 和腹内侧核 (VMN) 通过行为和代谢机制调节能量平衡。垂体腺苷酸环化酶激活肽 (PACAP) 的受体在这些核中大量表达，表明 PACAP 可能对摄食行为和体重调节至关重要。为了描述归因于特定下丘脑细胞群的独特行为和生理反应，将 PACAP 特异性注射到 PVN 或 VMN 中。总体食物摄入量在两个部位均显著减少；然而，进餐模式分析表明，只有注射到 PVN 才会导致进餐量、持续时间和总进食时间的显著减少。PVN 和 VMN 中的 PACAP 介导的摄食减少被 PAC1R 拮抗剂消除，而预先给予 VPACR 拮抗剂则没有影响。PACAP 注射到 VMN 会引起代谢参数的独特变化，包括核心体温和自发运动活动的显著增加，这些变化依赖于 PAC1R，而 PVN 注射 PACAP 则没有影响。最后，使用神经元示踪剂霍乱毒素亚单位 B (CTB) 将单侧注射到 PVN 或 VMN 中，鉴定了含有 PACAP 的传入纤维。PVN 注射的 CTB 信号与 medial anterior bed nucleus of the stria terminalis、VMN 和 lateral parabrachial nucleus (LPB) 中的 PACAP mRNA 共定位，而 VMN 注射的 CTB 信号与 medial amygdala 和 LPB 中的 PACAP mRNA 高度共定位。这些脑区已知会影响能量平衡，部分原因可能是通过 PACAP 投射到 PVN 和 VMN。
