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P1‐148: Progressive neurofibrillary degeneration does not induce loss of pyramidal neurons in the cortex of the novel transgenic rat model for human tauopathy
Author(s) -
Bugos Ondrej,
Zilka Norbert,
Kucerak Juraj,
Koson Peter,
Novak Petr,
Handzusova Martina,
Filipcik Peter,
Novak Michal
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.697
Subject(s) - tauopathy , neurodegeneration , tau protein , genetically modified mouse , hippocampus , transgene , neuroscience , senile plaques , thioflavin , pathology , cortex (anatomy) , biology , alzheimer's disease , medicine , biochemistry , disease , gene
paramagnetic resonance we observed significantly increased accumulation of ascorbyl free radicals in brains of transgenic animals (up to 1.5-fold increase; P < 0.01). Moreover, dysregulation of apoptotic and oxidative stress response genes was determined in these animals. We found significant up-regulation of anti-apoptotic gene from Bcl-2 family (up to 2.7fold increase) that is involved in mitochondrial membrane potential regulation and control of the production of reactive oxygen species. In line with the data transgene-expressing primary neurons harboured significantly increased levels of depolarized mitochondria (w1.2-fold above control) suggesting protective role of Bcl-x up-regulation in neurodegeneration. Conclusions: These data demonstrate impaired redox balance, increased oxidative stress and anti-apoptotic markers elevation induced by misfolded truncated tau expression. Furthermore, dysregulation of genes involved in apoptotic and redox pathways correlates to mitochondrial dysfunction and free radicals elevation in transgenic rat model. Moreover, our results indicate that toxic gain of function of human misfolded tau is associated with activation of anti-apoptotic defense mechanisms. This work was supported by research funding agencies of Slovak republic: APVV No. 0634-07, LPP-0043-09 and international agency: ICGEB grant No. CRP/SVK08-01.