title: Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits.
abstract: Regulation of the formation and rewiring of neural circuits by neuropeptides may require coordinated production of these signaling molecules and their receptors that may be established at the transcriptional level. Here, we address this hypothesis by comparing absolute expression levels of opioid peptides with their receptors, the largest neuropeptide family, and by characterizing coexpression (transcriptionally coordinated) patterns of these genes. We demonstrated that expression patterns of opioid genes highly correlate within and across functionally and anatomically different areas. Opioid peptide genes, compared with their receptor genes, are transcribed at much greater absolute levels, which suggests formation of a neuropeptide cloud that covers the receptor-expressed circuits. Surprisingly, we found that both expression levels and the proportion of opioid receptors are strongly lateralized in the spinal cord, interregional coexpression patterns are side specific, and intraregional coexpression profiles are affected differently by left- and right-side unilateral body injury. We propose that opioid genes are regulated as interconnected components of the same molecular system distributed between distinct anatomic regions. The striking feature of this system is its asymmetric coexpression patterns, which suggest side-specific regulation of selective neural circuits by opioid neurohormones.-Kononenko, O., Galatenko, V., Andersson, M., Bazov, I., Watanabe, H., Zhou, X. W., Iatsyshyna, A., Mityakina, I., Yakovleva, T., Sarkisyan, D., Ponomarev, I., Krishtal, O., Marklund, N., Tonevitsky, A., Adkins, D. L., Bakalkin, G. Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.|Key State Laboratory, Bogomoletz Institute of Physiology, Kiev, Ukraine.
authors.forename: Olga
authors.initials: O
authors.lastname: Kononenko
authors.affiliation: Moscow State University, Moscow, Russia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Galatenko
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Andersson
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden; igor.bazov@farmbio.uu.se.
authors.forename: Igor
authors.initials: I
authors.lastname: Bazov
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Xing Wu
authors.initials: XW
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.|Department of Human Genetics, Institute of Molecular Biology and Genetics, Kiev, Ukraine.
authors.forename: Anna
authors.initials: A
authors.lastname: Iatsyshyna
authors.affiliation: Moscow State University, Moscow, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Mityakina
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Yakovleva
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Daniil
authors.initials: D
authors.lastname: Sarkisyan
authors.affiliation: Waggoner Center for Alcohol and Addiction Research and The College of Pharmacy, The University of Texas, Austin, Texas, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Ponomarev
authors.affiliation: Key State Laboratory, Bogomoletz Institute of Physiology, Kiev, Ukraine.
authors.forename: Oleg
authors.initials: O
authors.lastname: Krishtal
authors.affiliation: Department of Neuroscience, Section of Neurosurgery, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Marklund
authors.affiliation: Moscow State University, Moscow, Russia.
authors.forename: Alex
authors.initials: A
authors.lastname: Tonevitsky
authors.affiliation: Department of Neuroscience, College of Medicine, and.|Department of Health Sciences and Research, College of Health Professions, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: DeAnna L
authors.initials: DL
authors.lastname: Adkins
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Georgy
authors.initials: G
authors.lastname: Bakalkin
mesh_terms: D000701:Analgesics, Opioid / Q000378:metabolism*; D000818:Animals; D008297:Male; D009415:Nerve Net / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D010146:Pain / Q000378:metabolism; D020318:Rats, Long-Evans; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D009479:Neuropeptides; D011957:Receptors, Opioid
keywords: lateralization; neuropeptides; spinal cord