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The Left-Right Side-Specific Neuroendocrine Signaling from Injured Brain: An Organizational Principle.

Hiroyuki Watanabe1,2, Yaromir Kobikov3, Olga Nosova1

  • 1Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, SE-751 24, Sweden.

Function (Oxford, England)
|July 10, 2024
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Summary

A novel topographic neuroendocrine system (T-NES) has left and right sides that mediate brain injury effects differently. These distinct pathways involve unique neural mechanisms and molecular networks, challenging previous neurological dogma.

Keywords:
brain injurycontralateral effectsgene co-expression networkshumoral signalingleft-right patternsmotor deficitsneuroendocrine systempostural asymmetry

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Molecular Biology

Background:

  • Neurological deficits after brain injury are traditionally attributed to crossed descending neural tracts.
  • A novel topographic neuroendocrine system (T-NES) was recently identified, operating via humoral pathways to mediate side-specific effects of unilateral brain lesions.

Purpose of the Study:

  • To investigate if the T-NES comprises distinct left and right counterparts.
  • To determine if these counterparts differ in their neural and molecular mechanisms.

Main Methods:

  • Experiments were conducted on rats with transected thoracic spinal cords.
  • Opioid antagonists were used to block hormonal signaling.
  • Spinal deafferentation and cervical spinal cord transections were performed.
  • Gene-gene co-expression patterns were analyzed.

Main Results:

  • Left- and right-sided hormonal signaling in T-NES were differentially affected by opioid antagonists.
  • Left and right neurohormonal pathways targeted afferent spinal mechanisms differently.
  • The sympathetic nervous system was ruled out as the signaling pathway.
  • Distinct left- and right-side-specific gene co-expression networks were identified, coordinated via the hypothalamus and lumbar spinal cord.

Conclusions:

  • The T-NES is bipartite, with distinct left and right components.
  • These components contribute to contralateral neurological deficits via different neural mechanisms.
  • The T-NES may facilitate ipsilateral regulation of molecular and neural processes across distant neural areas.