Bioscience seminar series

  • Date: –09:45
  • Location: Join Zoom Meeting
  • Lecturer: Prof. Georgy Bakalkin and Olga Nosova, Department of Pharmaceutical Biosciences; Molecular Neuropsychopharmacology group
  • Organiser: Bioscience Seminar Team
  • Contact person: Anna Nilsson
  • Seminarium

The Left-Right Side-Specific Endocrine System: Challenging the Neurological Dogma

Neural tracts descending from the left hemisphere regulate movement of the right limbs, whereas the left limbs are controlled by the right hemisphere. Damage to these tracts by brain trauma or stroke often occur on one side of the body, and causes asymmetric changes in posture, movement, and muscle reflexes of the limbs.

We previously identified neurohormones that induce an asymmetric postural response in normal rats. An unusual observation was that the left hindlimb flexion was caused by one group of neurohormones, whereas a different group of hormones produced flexion on the right side. These hormones are synthesized in the pituitary, the “master” endocrine gland. The side-specific postural changes induced by the neurohormones mimicked the effects of unilateral brain lesion.

We then asked if pituitary hormones could mediate the side-specific effects of unilateral brain injury on posture and reflexes. To investigate this, we analyzed the effects of a unilateral brain lesion in rats in which the brain and the lumbar spinal cord were surgically disconnected. Injury of the hindlimb sensorimotor cortex in rats with transected spinal cords produced hindlimb postural asymmetry with contralateral flexion, and contralesional activation of hindlimb reflexes. To examine a role of the endocrine system, the pituitary gland was surgically removed. This abolished the injury-induced effects. β-endorphin and Arg-vasopressin were then identified as pituitary hormones that induced right-side hindlimb responses in animals without brain injury. Consistently, small-molecule antagonists of these hormones inhibited the effects of the left brain injury.

This study reveals the previously unknown left-right side-specific humoral signaling from the injured brain to the hindlimbs. Pharmacological targeting of this topographical endocrine mechanism may be beneficial for treatment of lateralized postural and motor deficits. From a biological standpoint, the mechanism may control a balance between the left–right processes in bilaterally symmetric animals.

Recent papers:

Lukoyanov et al., Endocrine signaling mediates asymmetric motor responses after unilateral brain injury. Deposited at bioRxiv: 2020.04.23.056937.

Bakalkin et al., Unilateral traumatic brain injury of the left and right hemisphere produces the left hindlimb response in rats. Experimental Brain Res. In Press.

Watanabe et al., Left-right side-specific neuropeptide mechanism mediates contralateral responses to a unilateral brain injury. eNeuro. 2021, doi: 10.1523/ENEURO.0548-20.2021.

Carvalho et al., Unilateral brain injury to pregnant rats induces asymmetric neurological deficits in the offspring. Eur J Neurosci. 2021, doi: 10.1111/ejn.15243.

Watanabe et al., Ipsilesional versus contralesional postural deficits induced by unilateral brain trauma: a side reversal by opioid mechanism. Brain Commun. 2020, 2: fcaa208. doi: 10.1093/braincomms/fcaa208.

Zhang et al., Hindlimb motor responses to unilateral brain injury: spinal cord encoding and left-right asymmetry. Brain Commun. 2020, 2: fcaa055. doi: 10.1093/braincomms/fcaa055.

Kononenko et al., Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits.

FASEB J. 2017 31: 1953-1963, doi: 10.1096/fj.201601039R.

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