Repository of Research and Investigative Information

Repository of Research and Investigative Information

Hormozgan University of Medical Sciences

Complexity of Compensatory Effects in Nrf1 Knockdown: Linking Undeveloped Anxiety-Like Behavior to Prevented Mitochondrial Dysfunction and Oxidative Stress

(2016) Complexity of Compensatory Effects in Nrf1 Knockdown: Linking Undeveloped Anxiety-Like Behavior to Prevented Mitochondrial Dysfunction and Oxidative Stress. Cellular and Molecular Neurobiology.


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Anxiety-related disorders are complex illnesses that underlying molecular mechanisms need to be understood. Mitochondria stand as an important link between energy metabolism, oxidative stress, and anxiety. The nuclear factor, erythroid-derived 2,-like 1(Nrf1) is a member of the cap “n” collar subfamily of basic region leucine zipper transcription factors and plays the major role in regulating the adaptive response to oxidants and electrophiles within the cell. Here, we injected small interfering RNA (siRNA) targeting Nrf1 in dorsal third ventricle of adult male albino Wistar rats and subsequently examined the effect of this silencing on anxiety-related behavior. We also evaluated apoptotic markers and mitochondrial biogenesis factors, along with electron transport chain activity in three brain regions: hippocampus, amygdala, and prefrontal cortex. Our data revealed that in the group that received Nrf1-siRNA, anxiety-related behavior did not show any significant changes compared to the control group. Caspase-3 did not increase in Nrf1-siRNA-injected rats even though Bax/Bcl2 ratio markedly elevated in Nrf1-knockdown rats in all three mentioned regions compared to control rats. Also, Nrf1 silencing of complex I and II–III did not alter, generally. In addition, Nrf1-knockdown affected mitochondrial biogenesis markers. The level of peroxisome proliferator-activated receptor gamma coactivator-1α and cytochrome-c increased, which indicates a possible role for mitochondrial biogenesis in anxiety. © 2015, Springer Science+Business Media New York.

Item Type: Article
Additional Information: cited By 1
Keywords: cytochrome c; peroxisome proliferator activated receptor gamma coactivator 1alpha; small interfering RNA; transcription factor Nrf1; transcription factor Nrf2; caspase 3; messenger RNA; nuclear respiratory factor 1; protein Bax; small interfering RNA, amygdala; animal experiment; animal model; anxiety disorder; apoptosis; Article; brain third ventricle; disorders of mitochondrial functions; gene silencing; hippocampus; male; mitochondrial biogenesis; nonhuman; oxidative stress; prefrontal cortex; priority journal; rat; respiratory chain; spectrophotometry; stereotaxic surgery; animal; animal behavior; anxiety; brain; electron transport; enzymology; gene silencing; genetics; metabolism; mitochondrion; organelle biogenesis; pathology; Western blotting; Wistar rat, Animals; Anxiety; Apoptosis; bcl-2-Associated X Protein; Behavior, Animal; Blotting, Western; Brain; Caspase 3; Electron Transport; Gene Knockdown Techniques; Gene Silencing; Male; Mitochondria; Nuclear Respiratory Factor 1; Organelle Biogenesis; Oxidative Stress; Rats, Wistar; RNA, Messenger; RNA, Small Interfering
Subjects: QT Physiology > QT104-172 Human Physiology
Divisions: Education Vice-Chancellor Department > Faculty of Medicine > Department of Basic Science > Department of Physiology Medical
Depositing User: مهندس هدی فهیم پور

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