Hypothalamic nuclei are malformed in weanling offspring of low protein malnourished rat dams
Hypothalamic nuclei are malformed in weanling offspring of low protein malnourished rat dams
复制标题
DOI：
10.1093/jn/130.10.2582
复制
发表时间：
2000-10-01
影响因子：
4.2
通讯作者：
Dörner, G
中科院分区：
文献类型：
--
作者：
Plagemann, A;Harder, T;Dörner, G
妊娠期和哺乳期母体低蛋白营养不良（LP）是一种经常用于研究围产期生长迟缓长期有害后果的动物模型。围产期营养不良和出生时生长迟缓都是日后患糖尿病和心血管疾病的危险因素。其病理生理机制尚不清楚。下丘脑核团决定性地参与中枢神经对食物摄入、体重和代谢的调节。（8%蛋白质;对照饮食，17%蛋白质）对断奶时后代体重和代谢的下丘脑调节因子的组织的影响在出生后20天，LP组仔鼠体重显著低于对照组仔鼠（CO; P <0.001），并伴有低血糖和低胰岛素血症（P <0.005）。下丘脑腹内侧核的相对体积（P <0.01）和Nissl染色神经元的数密度（P <0.01）以及下丘脑室旁核（PVN; P <0.001）均明显增大。与此相反，LP后代和CO后代之间的下丘脑外侧区，下丘脑弓状核（ARC）和下丘脑背内侧核的神经元密度没有显着差异。另一方面，LP后代在ARC中显示较少的神经肽Y免疫阳性神经元（P <0.05），而在PVN中，LP后代与CO后代相比，发现较低的神经元密度的甘丙肽免疫阳性神经元（P <0.001）。相反，在PVN，胆囊收缩素-8S阳性神经元的数密度没有显着的组间差异。表明这些特定的下丘脑变化对LP后代晚年的体重和代谢产生长期影响。
Maternal low protein malnutrition during gestation and lactation (LP) is an animal model frequently used for the investigation of long-term deleterious consequences of perinatal growth retardation. Both perinatal malnutrition and growth retardation at birth are risk factors for diabetic and cardiovascular disturbances in later life. The pathophysiologic mechanisms responsible are unknown. Hypothalamic nuclei are decisively involved in the central nervous regulation of food intake, body weight and metabolism, We investigated effects of a low protein diet (8% protein; control diet, 17% protein) during gestation and lactation in rat dams on the organization of hypothalamic regulators of body weight and metabolism in the offspring at weaning (d 20 of life), LP offspring had significantly lower body weight than control offspring (CO; P < 0.001), associated with hypoglycemia and hypoinsulinemia (P < 0.005) on d 20 of life. This was accompanied by a greater relative volume of the ventromedial hypothalamic nucleus (P < 0.01) and a greater numerical density of Nissl-stained neurons in this nucleus (P < 0.01) as well as in the paraventricular hypothalamic nucleus (PVN; P < 0.001). In contrast, no significant differences in neuronal densities were observed generally in the lateral hypothalamic area, arcuate hypothalamic nucleus (ARC), and dorsomedial hypothalamic nucleus between LP offspring and CO offspring. On the other hand, LP offspring displayed fewer neurons immunopositive for neuropeptide Y in the ARC (P < 0.05), whereas in the PVN, lower neuronal densities of neurons immunopositive for galanin were found in LP offspring compared with CO offspring (P < 0.001). On the contrary, in the PVN, no significant group difference in the numerical density of cholecystokinin-8S-positive neurons was present. A long-term effect of these specific hypothalamic alterations on body weight and metabolism in LP offspring during later life is suggested.