T. Casoli, G. Di Stefano, A. Delfino, C. Bertoni-Freddari

The most widely accepted physiological function of vitamin E is its role as an important antioxidant in membranes, preventing oxidative damage to polyunsaturated lipids in the lipid bilayer. The brain is thought to be particularly vulnerable to oxidative stress due to its high rate of oxygen consumption along with its poor catalase activity and moderate amounts of superoxide dismutase and glutathione peroxidase. Moreover, it is known that the neurological abnormalities observed during aging are similar to those observed in vitamin E deficiency. In order to study the effect of vitamin E deficiency on neuronal plasticity we evaluated the expression levels of GAP-43 and MAP-2, two proteins involved respectively in axonal and dendritic remodeling. Control adult (11 months), old (24 months) and vitamin E-deficient (11 months) Wistar rats were analyzed in this study. Rats fed with a vitamin E-deficient diet received a vitamin E lacking chow for a period of ten months. mRNA levels were determined by means of in situ hybridization procedure in selected subregions of hippocampus (dentate gyrus, CA1 and CA3) and cerebellum (granule cell layer). MAP-2 and GAP-43 mRNAs showed different patterns of changes following vitamin E-deficiency and aging. Cerebellar level of MAP-2 expression did not change in both cases studied as compared to control rats, while hippocampal levels showed a decrease in all areas analyzed and in both models of degeneration, especially in CA1 pyramidal cells (-43% in vitamin E-deficient rats and –58% in aged rats), in comparison with adult animals. Considering that previous investigations demonstrated a marked decrease of MAP-2 levels in hippocampus of aged and vitamin E deprived rats, we can conclude that changes at trascriptional levels parallel those at translation levels in these models of neurodegeneration. GAP-43 mRNA showed, on the contrary, a remarkable decrease both in aging and vitamin E-deprived rats in cerebellar granular layer, while only CA3 mRNA decreased significantly in vitamin E-deficient rats when compared to adult and old animals. Taking into account previous results on GAP-43 levels (unaltered levels of GAP-43 in cerebellar molecular layer in aged rat compared to adult animals and in CA3 axons in vitamin E-deprived rats compared to old and adult animals) we can conclude that there is a lack of correlation for this protein between mRNA and protein under conditions of vitamin E deficiency and aging. These results suggest that oxidative stress and aging negatively affect neuroplasticity in the central nervous system showing different characteristics at dendritic and axonal level.

Keywords (Optional): 
in situ hybridization
vitamin E-deficiency