Hypothalamic Nuclei Are Malformed in Weanling Offspring of Low Protein Malnourished Rat Dams

Abstract

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.