Induced expression of neurotrophins in transgenic mice overexpressing ornithine decarboxylase and overproducing putrescine.
Transgenic mice overexpressing ornithine decarboxylase (ODC) were recently generated (Halmekytö et al.: Biochem Biophys Res Commun 180:262-267, 1991). The dramatic ODC overexpression resulted in a very high accumulation of the polyamine putrescine in the brain. As elevated polyamine levels in the brain are believed to be associated with neuronal damage, we studied whether enhanced putrescine accumulation in the brain of these mice affects the expression of neurotrophins and their high affinity receptors. Northern blot analysis indicated that mRNA levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3) were significantly elevated about 1.5-fold in the hippocampus of ODC transgenic mice as compared with control animals. The levels of BDNF, NGF and NT-3 mRNA were also elevated in the kidneys of the transgenic mice. In eight other tissues examined there were no significant differences. The expression pattern of BDNF mRNA and of trkB and trkC (high affinity receptors for BDNF and NT-3 respectively) immunoreactivity in the hippocampal formation did not reveal significant differences. The induction of the expression of neurotrophins could belong to neuroprotective measures triggered by ODC overexpression.
Reeben
M
M
Department of Neurology, University of Kuopio, Finland.
Arbatova
J
J
Palgi
J
J
Miettinen
R
R
Halmekytö
M
M
Alhonen
L
L
Jänne
J
J
Riekkinen
P
P
Saarma
M
M
D000818:Animals; D015152:Blotting, Northern; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D020933:Neurotrophin 3; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011700:Putrescine / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D014018:Tissue Distribution
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D009955:Ornithine Decarboxylase; D011700:Putrescine