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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 \u03b4-, \u03ba- and \u00b5-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\u2013gene 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.<\/jats:p>","DOI":"10.1093\/function\/zqae013","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T15:24:53Z","timestamp":1710257093000},"source":"Crossref","is-referenced-by-count":5,"title":["The Left-Right Side-Specific Neuroendocrine Signaling from Injured Brain: An Organizational Principle"],"prefix":"10.1152","volume":"5","author":[{"given":"Hiroyuki","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University , Uppsala, SE-751 24 , Sweden"},{"name":"Department of Molecular Medicine, University of Southern Denmark , Odense, DK-5230 , Denmark"}]},{"given":"Yaromir","family":"Kobikov","sequence":"additional","affiliation":[{"name":"Volunteer Associate at Department of Pharmaceutical Biosciences, Uppsala University , Uppsala, SE-751 24 , Sweden"}]},{"given":"Olga","family":"Nosova","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University , Uppsala, SE-751 24 , Sweden"}]},{"given":"Daniil","family":"Sarkisyan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University , Uppsala, SE-751 24 , Sweden"},{"name":"Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University , Uppsala, SE-751 08 , Sweden"}]},{"given":"Vladimir","family":"Galatenko","sequence":"additional","affiliation":[{"name":"Evotec International GmbH , G\u00f6ttingen 37079 , Germany"}]},{"given":"Liliana","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina da Faculdade de Medicina da Universidade do Porto , Porto 4200-319 , Portugal"}]},{"given":"Gisela H","family":"Maia","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade Translacional e Biotecnologia M\u00e9dica (TBIO)\/Rede de Investiga\u00e7\u00e3o em Sa\u00fade (RISE-Health), Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto , Porto 4200-072 , Portugal"},{"name":"Medibrain , Vila do Conde 4480-807 , Portugal"},{"name":"Brain Research Institute , Porto 4450-208 , Portugal"}]},{"given":"Nikolay","family":"Lukoyanov","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina da Faculdade de Medicina da Universidade do Porto , Porto 4200-319 , Portugal"},{"name":"Brain Research Institute , Porto 4450-208 , Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto , Porto 4200-135 , 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