The effect of low protein diet in pregnancy on the development of brain metabolism in rat offspring

The effect of maternal low protein diet in pregnancy on the function of offspring cerebral cytochrome c oxidase (CcO) was investigated in vitro immediately before and after birth, using fetal and neonatal rat pup forebrain tissue. Pregnant rat dams were fed either a control (C, 18% casein n = 22) or low protein (LP,9% casein n = 14) diet. Cerebral tissues were harvested from pups the day before (E21) and after (P1) birth. A Clarke electrode chamber was used to determine O-2 consumption in brain tissue homogenate, under baseline conditions with and without the mitochondrial electron transport chain inhibitor myxothiazol and in the presence of incremental doses of the electron donor N',N',N',N'-tetramethyl-p-phenylenediamide (TMPD) with myxothiazol. Maximal stimulated CcO activity (V-O2 (max)) was less in LP versus C pups at both E21 (P < 0.001) and PI (P < 0.05). At E21 only, sensitivity to electron flux (pEC(50)) was greater (P < 0.001) in LP compared to C offspring. In addition, V-O2 max was reduced and pEC(50) was greater after birth (i.e. P1 versus E21) in C (P < 0.001) but not in LP pups. This is the first report of the effects of maternal dietary imbalance in pregnancy on offspring cerebral metabolic function. The effects may form part of a developmental adaptive response to reduce energy consumption and promote perinatal survival, or to confer advantage in a postnatal environment predicted to be nutritionally poor.