Vitamin E-deficiency and aging effect on expression levels of GAP-43 and MAP-2 in selected areas of the brain
T. Casoli, G. Di Stefano, A. Delfino, C. Bertoni-Freddari
Neurobiology of Aging Laboratory, INRCA Research Department, Via Birarelli 8, 60121 Ancona, Italy
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.
Key words:
MAP-2, GAP-43, aging, in situ hybridization, vitamin E-deficiency
Problems or questions regarding this site should be directed to
the organiser