Effects of pre-weaning undernutrition and post-weaning rehabilitation on polyphosphoinositide pools in rat brain regions

Abstract

In order to assess the effects of undernutrition during the pre-weaning period on polyphosphoinositide (PolyPI) pools in rat cerebral cortex, brain stem, and cerebellum, dams were fed 5% (L⁻) or 22% (L⁺) protein diets from birth to weaning and the pups were used at this age for analyses. To examine rehabilitation post-weaning, L⁻ and L⁺ pups were fed 22% protein diets (P⁺) for an additional six week period. Rats were decapitated and the dissection begun either immediately (“0 min” samples) or 10 min later (10 min samples). Body and tissue weights, and cerebroside levels were determined in addition to PolyPI concentrations. In brain the extent of disappearance of PolyPI during the 10 min post-mortem period paralleled the content of gray matter: cerebral cortex > cerebellum > brain stem in all groups regardless of diet. Levels of PtdIns4P and PtdIns4,5P₂ were decreased by 40% and 70% respectively in cerebral cortex of L⁻ “0 min” samples. Deficits of both lipids in brain stem and cerebellum were 40–50%. In the L⁻ 10 min samples, deficits were 20–30% in all three regions as compared with L⁺ 10 min levels, indicating the presence of a portion of both lipids affected only moderately by nutritional insufficiency. The effects on this relatively inert pool, much of it localized in myelin, were reversed on nutritional rehabilitation. The Poly PI pool lost post-mortem in L⁺ brain regions was practically absent in L⁻ brain regions and was not restored in L⁻ P⁺ animals. Thus, this study indicates that a metabolically labile pool, primarily located in gray matter structures, is more sensitive to nutritional deprivation during the pre-weaning period than the more stable pool. The precise role and function of these pools remain to be determined.