title: Complexity of Compensatory Effects in Nrf1 Knockdown: Linking Undeveloped Anxiety-Like Behavior to Prevented Mitochondrial Dysfunction and Oxidative Stress.
abstract: 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.
authors.affiliation: Department of Animal Physiology, Faculty of Biology, Kharazmi University, P.O. Box: 15614, Tehran, Iran. soolmaz25kh@yahoo.com.|Medical Genomics Research Center and School of Advanced Sciences in Medicine, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. soolmaz25kh@yahoo.com.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Khalifeh
authors.affiliation: Department of Animal Physiology, Faculty of Biology, Kharazmi University, P.O. Box: 15614, Tehran, Iran.
authors.forename: Shahrbanoo
authors.initials: S
authors.lastname: Oryan
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Digaleh
authors.affiliation: Department of Physiology, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaerzadeh
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Nader
authors.initials: N
authors.lastname: Maghsoudi
authors.affiliation: Medical Genomics Research Center and School of Advanced Sciences in Medicine, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.|Institute for Cognitive Science Studies (ICSS), Tehran, Iran.|School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000818:Animals; D001007:Anxiety / Q000473:pathology*; D017209:Apoptosis; D001522:Behavior, Animal; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D004579:Electron Transport; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism*; D001678:Organelle Biogenesis; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000378:metabolism; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051266:Nuclear Respiratory Factor 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D053148:Caspase 3
keywords: Anxiety; Electron transport chain; Nrf1; PGC-1α; siRNA