Early undernutrition increases glycogen content and reduces the activated forms of GSK3, AMPK, p38 MAPK, and JNK in the cerebral cortex of suckling rats.
Exposure to maternal undernutrition during development increases the risk for neurological and cognitive defects. However, little is known about the underlying mechanisms involved. Peripheral responses to insulin are increased following food-restriction, thus the possibility arises that brain insulin actions are affected by undernutrition, causing damages to the higher cerebral functions. In this study, we examined the effects of early undernutriton on molecular targets of insulin actions such as glucose transporters, glycogen, glycogen synthase kinase-3 (GSK3) and mitogen-activated protein kinases, as well as proteins involved in apoptosis in the cortex from 10-day-old rats. We show that undernutrition results in an enhanced glycogen content which is confined to astrocytes, according to our histochemical approaches. Cortical phospho-GSK3 is also increased. In addition to glycogen synthesis, GSK3 regulates crucial cellular processes. Therefore, its elevated degree of phosphorylation may have an impact on these processes and, consequently, on the cortical development. Phospho-p38 and both total JNK and phospho-JNK, which regulate apoptosis, are reduced following undernutrition. However, cleaved caspase 3 is not altered, which suggests that this condition does not induce extensive modifications to the cortical apoptosis. Thus, our results indicate that undernutrition gives rise to molecular alterations that may have repercussions on cerebral cortex development and functions.
Lizárraga-Mollinedo
Esther
E
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
Fernández-Millán
Elisa
E
de Miguel-Santos
Laura
L
Martínez-Honduvilla
Carlos José
CJ
Alvarez
Carmen
C
Escrivá
Fernando
F
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling / Q000254:growth & development / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002540:Cerebral Cortex / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006003:Glycogen / Q000096:biosynthesis*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D044342:Malnutrition / Q000201:enzymology*; D009929:Organ Size / Q000502:physiology; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D006003:Glycogen; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases