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The left-right side-specific neuroendocrine signaling from injured brain: An organizational principle

2024-03-14Research article Open access
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dc.contributor.authorWatanabe, Hiroyuki
dc.contributor.authorHenrique Maia, Gisela Maria
dc.contributor.authorKobikov, Yaromir
dc.contributor.authorNosova, Olga
dc.contributor.authorSarkisyan, Daniil
dc.contributor.authorGalatenko, Vladimir
dc.contributor.authorCarvalho, Liliana
dc.contributor.authorMaia, Gisela H.
dc.contributor.authorLukoyanov, Nikolay
dc.contributor.authorLavrov, Igor
dc.contributor.authorOssipov, Michael H.
dc.contributor.authorHallberg, Mathias
dc.contributor.authorSchouenborg, Jens
dc.contributor.authorZhang, Mengliang
dc.contributor.authorBakalkin, Georgy
dc.date.accessioned2025-07-08T08:44:25Z
dc.date.available2025-07-08T08:44:25Z
dc.date.issued2024-03-14
dc.description.abstractA neurological dogma is that the contralateral effects of brain injury are set through crossed descending neural tracts. We have recently identified a novel topographic neuroendocrine system (T-NES) that operates via a humoral pathway and mediates the left-right side-specific effects of unilateral brain lesions. In rats with completely transected thoracic spinal cords, unilateral injury to the sensorimotor cortex produced contralateral hindlimb flexion, a proxy for neurological deficit. Here, we investigated in acute experiments whether T-NES consists of left and right counterparts and whether they differ in neural and molecular mechanisms. We demonstrated that left- and right-sided hormonal signaling is differentially blocked by the δ-, κ- and µ-opioid antagonists. Left and right neurohormonal signaling differed in targeting the afferent spinal mechanisms. Bilateral deafferentation of the lumbar spinal cord abolished the hormone-mediated effects of the left-brain injury but not the right-sided lesion. The sympathetic nervous system was ruled out as a brain-to-spinal cord-signaling pathway since hindlimb responses were induced in rats with cervical spinal cord transections that were rostral to the preganglionic sympathetic neurons. Analysis of gene–gene co-expression patterns identified the left- and right-side-specific gene co-expression networks that were coordinated via the humoral pathway across the hypothalamus and lumbar spinal cord. The coordination was ipsilateral and disrupted by brain injury. These findings suggest that T-NES is bipartite and that its left and right counterparts contribute to contralateral neurological deficits through distinct neural mechanisms, and may enable ipsilateral regulation of molecular and neural processes across distant neural areas along the neuraxis.por
dc.description.sponsorship[Grants K2014-62X-12190-19-5, 2019-01771-3, and 2022-01182]; [NNF20OC0065099]
dc.identifier.citationWatanabe, H., Kobikov, Y., Nosova, O., Sarkisyan, D., Galatenko, V., Carvalho, L., Maia, G. H., Lukoyanov, N., Lavrov, I., Ossipov, M. H., Hallberg, M., Schouenborg, J., Zhang, M., & Bakalkin, G. (2024). The left-right side-specific neuroendocrine signaling from injured brain: An organizational principle. Function, 5(4), zqae013. https://doi.org/10.1093/function/zqae013
dc.identifier.doi10.1093/function/zqae013
dc.identifier.eissn2633-8823
dc.identifier.urihttp://hdl.handle.net/10400.22/30210
dc.language.isoeng
dc.peerreviewedn/a
dc.publisherOXFORD Academic
dc.relation.hasversionhttps://academic.oup.com/function/article/5/4/zqae013/7629141
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHumoral signaling
dc.subjectNeuroendocrine system
dc.subjectGene co-expression networks
dc.subjectLeft-right patterns
dc.subjectBrain injury
dc.subjectContralateral effects
dc.subjectMotor deficits
dc.subjectPostural asymmetry
dc.titleThe left-right side-specific neuroendocrine signaling from injured brain: An organizational principlepor
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.endPage23
oaire.citation.issue4
oaire.citation.startPage1
oaire.citation.titleFunction
oaire.citation.volume5
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameHenrique Maia
person.givenNameGisela Maria
person.identifier.ciencia-id2014-5C31-EBF4
person.identifier.orcid0000-0002-3199-340X
relation.isAuthorOfPublication0bdd4bff-1f99-4630-b3c2-d5759b95a2eb
relation.isAuthorOfPublication.latestForDiscovery0bdd4bff-1f99-4630-b3c2-d5759b95a2eb

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