Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits

Olga Kononenko, Vladimir Galatenko, Malin Andersson, Igor Bazov, Hiroyuki Watanabe, Xing Wu Zhou, Anna Iatsyshyna, Irina Mityakina, Tatiana Yakovleva, Daniil Sarkisyan, Igor Ponomarev, Oleg Krishtal, Niklas Marklund, Alex Tonevitsky, DeAnna L Adkins, Georgy Bakalkin

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1953-1963
JournalFASEB Journal
Issue number5
Early online date2017 Jan 25
Publication statusPublished - 2017
Externally publishedYes


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