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Lukoyanov, N.

Publications and source records attributed to Lukoyanov, N..

3 recordsLinked to original sources

Hypothalamic asymmetry in hemisphere-specific neuroendocrine signaling

Brain lesions classically cause contralateral sensorimotor and postural deficits, attributed to the decussation of descending neural pathways. However, recent findings reveal that, beyond neural mechanisms, contralateral effects can also be mediated by the neuroendocrine system via humoral pathways. This raises the possibility that the brain regulates left- and right-sided peripheral processes through hypothalamic neurohormones released into the bloodstream. For such spatially targeted endocrine signaling to occur, hemisphere-specific neural activity must be encoded into side-specific hormonal output--requiring a lateralized organization of hypothalamic neuroendocrine systems. Here, we report molecular asymmetries in the rat hypothalamus that support this mechanism. Transcriptomic analysis revealed asymmetric expression of eleven neurohormonal genes, including Gnrh1, Cck, and Trh, along with distinct left-right side-specific gene co-expression networks. Chemogenetic stimulation of Arg-vasopressin neurons in vasopressin-hM3Dq-mCherry transgenic rats produced generalized changes in these networks--predominantly in the right hypothalamus--suggesting that hypothalamic neurohormonal circuits function as integrated, lateralized ensembles. Stereological analysis revealed asymmetric coordination of vasopressin neurons within the paraventricular nucleus, with the left rostral region decoupled from the right rostral and caudal subregions. Functionally, gonadotropin-releasing hormone, cholecystokinin-8, and thyrotropin-releasing hormone--administered intracisternally in rats with complete spinal cord transection--elicited side-specific peripheral responses, measured as hindlimb postural asymmetry in a binary left-right output model. These neurohormonal effects were therefore transmitted via the humoral route. These findings suggest that multiple hypothalamic neurohormones and their integrated networks are asymmetrically organized, and that their lateralization may be necessary for hemisphere-specific hormonal regulation of peripheral systems.

neuroscience↗

Bipartite left-right sided endocrine system: processing of contralateral effects of brain injury

The crossed descending neural tracts set a basis for contralateral effects of brain injury. In addition, the left-right side-specific effects of the unilateral brain lesions may be mediated by neurohormones through the humoral pathway as discovered in animals with disabled descending motor tracts. We here examined if counterparts of the endocrine system that convey signals from the left and right brain injuries differ in neural and molecular mechanisms. In rats with completely transected cervical spinal cords a unilateral injury of the hindlimb sensorimotor cortex produced hindlimb postural asymmetry with contralateral hindlimb flexion, a proxy for neurological deficit. The effects of the left and right side brain lesions were differently inhibited by antagonists of the {delta}-, {kappa}- and {micro}-opioid receptors suggesting differential neuroendocrine control of the left-right side-specific hormonal signaling. Bilateral deafferentation of the lumbar spinal cord eliminated hormone-mediated effects of the left-side brain injury but not the right-side lesion suggesting their afferent and efferent mechanisms, respectively. Analysis of gene-gene co-expression patterns identified the left and right side-specific gene regulatory networks that were coordinated across the hypothalamus and lumbar spinal cord through the humoral pathway. The coordination was ipsilateral and perturbed by brain injury. These findings suggest that the neuroendocrine system that conveys left-right side-specific hormonal messages from injured brain is bipartite, contributes to contralateral neurological deficits through asymmetric neural mechanisms, and enables ipsilateral coordination of molecular processes across neural areas along the neuraxis. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=173 HEIGHT=200 SRC="FIGDIR/small/546857v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1d0ad6org.highwire.dtl.DTLVardef@b273f8org.highwire.dtl.DTLVardef@1dbac79org.highwire.dtl.DTLVardef@118599c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Endocrine signaling mediates asymmetric motor deficits after unilateral brain injury

A paradigm in neurology is that brain injury-induced motor deficits (e.g. hemiparesis and hemiplegia) arise due to aberrant activity of descending neural pathways. We discovered that a unilateral injury of the hindlimb sensorimotor cortex of rats with completely transected thoracic spinal cord produces hindlimb postural asymmetry with contralateral flexion, and asymmetric changes in nociceptive hindlimb withdrawal reflexes and gene expression patterns in lumbar spinal cord. The injury-induced postural effects were abolished by prior hypophysectomy and were mimicked by transfusion of serum from animals with unilateral brain injury. Antagonists of the opioid and vasopressin receptors blocked formation of hindlimb postural asymmetry suggesting that these neurohormones mediate effects of brain injury on lateralized motor responses. Our data indicate that descending neural control of spinal circuits is complemented by a previously unknown humoral signaling from injured brain to the contra- and ipsilesional hindlimbs, and suggest the existence of a body side-specific neuroendocrine regulation in bilaterally symmetric animals.

neuroscience↗