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2021 (English)In: eNeuro, E-ISSN 2373-2822, Vol. 8, no 3, article id 0548-20.2021Article in journal (Refereed) Published
Abstract [en]
Neuropeptides are implicated in control of lateralized processes in the brain. A unilateral brain injury (UBI) causes the contra- and ipsilesional side-specific postural and sensorimotor deficits. To examine whether opioid neuropeptides mediate UBI induced asymmetric processes we compared effects of opioid antagonists on the contra- and ipsilesional hindlimb responses to the left- and right-sided injury in rats. UBI induced hindlimb postural asymmetry (HL-PA) with the contralesional hindlimb flexion, and activated contralesional withdrawal reflex of extensor digitorum longus (EDL) evoked by electrical stimulation and recorded with EMG technique. No effects on the interossei (Int) and peroneaus longus (PL) were evident. The general opioid antagonist naloxone blocked postural effects, did not change EDL asymmetry while uncovered cryptic asymmetry in the PL and Int reflexes induced by UBI. Thus the spinal opioid system may either mediate or counteract the injury effects. Strikingly, effects of selective opioid antagonists were the injury side-specific. The mu- and kappa-antagonists beta-funaltrexamine and nor-binaltorphimine, respectively, reduced postural asymmetry after the right but not left UBI. In contrast, the delta-antagonist naltrindole inhibited HL-PA after the left but not right side brain injury. The opioid gene expression and opioid peptides were lateralized in the lumbar spinal cord, and coordination between expression of the opioid and neuroplasticity-related genes was impaired by UBI that together may underlie the side-specific effects of the antagonists. We suggest that mirror-symmetric neural circuits that mediate effects of left and right brain injury on the contralesional hindlimbs are differentially controlled by the lateralized opioid system. Significance statement Functional specialization of the left and right hemispheres is an organizing principle of the brain. Lasting regulation of lateralized processes may be accomplished by paracrine neurohormonal mechanisms that preferentially operate in the left or right hemisphere. Our findings support this hypothesis by demonstration that mirror-symmetric neural circuits that control the left and right hindlimbs may be regulated by the left- and right-side specific neuropeptide mechanisms. Neuropeptides may differentially target the left and right counterparts of these circuits, and in this way control the left-right balance in their functional performance. This bipartite mechanism may be based on lateralization of the neuropeptide systems, and may operate in the spinal cord or control neural pathways descending from the brain to contralateral motoneurons.
Place, publisher, year, edition, pages
Society for Neuroscience, 2021
Keywords
brain injury, postural asymmetry, withdrawal reflexes, opioid system, left-right side specific regulation
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-461148 (URN)10.1523/ENEURO.0548-20.2021 (DOI)000719055700003 ()33903183 (PubMedID)
Funder
Swedish Research Council, K2014-62X-12190-19-5Swedish Research Council, 2019-01771-3Swedish Research Council, 2016-06195Lars Hierta Memorial FoundationP.O. Zetterling FoundationRegion Skåne, F2018/1490
2021-12-132021-12-132021-12-13Bibliographically approved