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Brain Region Specificity of Mitochondrial Biogenesis and Bioenergetics Response to Nrf2 Knockdown: A Comparison Among Hippocampus, Prefrontal Cortex and Amygdala of Male Rat Brain Publisher



Khalifeh S1, 2 ; Khodagholi F3, 4 ; Shaerzadeh F5 ; Ghazvini H6, 7 ; Zarrindast MR2, 8, 9 ; Azizi V10
Authors
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Authors Affiliations
  1. 1. Cognitive and Neuroscience research Center (CNRC) and School of Advanced Sciences in Medicine, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran
  2. 2. Medical Genomics Research Center and School of Advanced Sciences in Medicine, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
  3. 3. Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Molecular Medicine Research Center, Hormozgan Health institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  6. 6. Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran
  7. 7. Psychiatry and Behavioral Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran
  8. 8. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Institute for Cognitive Science Studies (ICSS), Tehran, Iran
  10. 10. Department of Animal Biology, Faculty of Biological Science, Shahid Beheshti University, Tehran, Iran

Source: Brazilian Archives of Biology and Technology Published:2017


Abstract

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been identified as the well-known coordinator of intracellular antioxidant defense system. Herein, we aimed to evaluate the effects of Nrf2 silencing on mitochondrial biogenesis markers peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a), nuclear respiratory factor-1(NRF-1), mitochondrial transcription factor A (TFAM) and cytochrome c as well activities of two enzymes citrate synthase (CS) and malate dehydrogenase (MDH) in three brain regions hippocampus, amygdala, and prefrontal cortex of male Wistar rats. Small interfering RNA (siRNA) targeting Nrf2 was injected in dorsal third ventricle. Next, western blot analysis and biochemical assays were used to evaluation of protein level of mitochondrial biogenesis factors and CS and MDH enzymes activity, respectively. Based on findings, whilst Nrf2-silencing led to notably reduction in protein level of mitochondrial biogenesis upstream PGC-1a in three brain regions compared to the control rats, the level of NRF-1, TFAM and cytochrome c remained unchanged. Furthermore, although Nrf2 silencing increased CS activity, activity of MDH significantly decreased in hippocampus and prefrontal cortex areas. Interestingly, CS and MDH activities in amygdala did not change after Nrf2 knockdown. In conclusion, the present findings highlighted complexity of interaction of Nrf2 and mitochondrial functions in a brain region-specific manner. However, by outlining the exact interaction between Nrf2 and mitochondria, it would be possible to find a new therapeutic strategies for neurological disorders related to oxidative stress.
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