Docosahexaenoic acid-deficient phosphatidyl serine and high alpha-tocopherol in a fetal mouse brain over-expressing Cu/Zn-superoxide dismutase.
The over-expressed Cu/Zn-superoxide dismutase (Cu/Zn-SOD) gene has been found in some circumstances phenotypically deleterious and associated with oxidative injury-mediated aberrations while in other studies it was considered neuroprotective. In this work we examine a number of biochemical markers in fetal and adult brain from transgenic (tg) mice expressing the human Cu/Zn-SOD gene, which may determine this dual characteristic. These markers include the polyunsaturated fatty acid (PUFA) profile in discrete phospholipid species, the alpha-tocopherol levels, a marker for lipid anti-oxidant status, and thiobarbituric acid reactive substance (TBARS), a marker for the tissue oxidative status. The PUFA profile in choline- and ethanolamine-phosphoglycerides was similar in tg and nontransgenic (ntg) animals of either fetal or adult brain. Serine-phosphoglycerides, however, showed a marked decrease from 20. 07+/-0.53 to 14.92+/-0.87 wt% and 14.52+/-1.15 wt% in docosahexaenoic acid (DHA; 22:6 n3), in the tg 51 and tg 69 fetal brains, respectively, but not in the comparable adult tissues. The alpha-tocopherol levels were significantly higher in the fetal compared to the adult brain. There were no differences in the anti-oxidant levels between the ntg and tg fetal brains, but there were differences in the adult animals; the tg mice were higher by at least two-fold than the control animals. The basal TBARS in the tg 51 fetal brain was 35% lower than that of ntg mouse and in the presence of Fe(2+), brain slices from the former released less TBARS (57% reduction) into the medium than the latter. These results suggest that higher dosages of Cu/Zn-SOD gene are compatible with increased alpha-tocopherol levels, reduced basal TBARS levels and a DHA deficiency in the fetal, but not the adult, tg brain.
Glozman
S
S
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Cerruti-Harris
C
C
Groner
Y
Y
Yavin
E
E
D000818:Animals; D000975:Antioxidants / Q000032:analysis*; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000032:analysis*; D004314:Down Syndrome / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010718:Phosphatidylserines / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014810:Vitamin E / Q000032:analysis*
D000975:Antioxidants; D010718:Phosphatidylserines; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D004281:Docosahexaenoic Acids; D013482:Superoxide Dismutase