Elevated spinal monoamine neurotransmitters after antenatal hypoxia-ischemia in rabbit cerebral palsy model

Alexander Drobyshevsky*, Silvia Honda Takada, Kehuan Luo, Matthew Derrick, Lei Yu, Katharina A. Quinlan, Jeannette Vasquez-Vivar, Maria Inês Nogueira, Sidhartha Tan

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

We hypothesized that a deficiency in the descending serotonergic input to spinal cord may underlie postnatal muscle hypertonia after global antenatal hypoxic-ischemic injury in a rabbit model of cerebral palsy. Neurotransmitter content was determined by HPLC in the spinal cord of newborns with and without muscle hypertonia after fetal global hypoxic-ischemic brain injury and naïve controls. Contrary to our hypothesis, serotonin levels in both cervical and lumbar expansions and norepinephrine in cervical expansion were increased in hypertonic kits relative to non-hypertonic kits and controls, with unchanged number of serotonergic cells in caudal raphe by stereological count. Serotonergic fiber length per unit of volume was also increased in hypertonic kits' cervical and lumbar spinal cord, both in dorsal and ventral horns. Gene expression of serotonin transporter was increased and 5-HTR2 receptors were decreased in hypertonic kits relative to controls in cervical and lumbar cord. Intrathecal administration of non-selective serotonin receptor inhibitor methysergide decreased muscle tone in hypertonic kits only. Conversely, intrathecal administration of serotonin solution increased muscle tone only in non-hypertonic kits. We speculate that maturation of serotonergic system in spinal cord may be directly affected by decreased corticospinal connectivity after antenatal hypoxic-ischemic brain injury.

Original languageEnglish (US)
Pages (from-to)394-402
Number of pages9
JournalJournal of neurochemistry
Volume132
Issue number4
DOIs
StatePublished - Feb 2015

Keywords

  • hypoxia-ischemia
  • muscle hypertonia
  • perinatal brain injury
  • serotonin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Drobyshevsky, A., Takada, S. H., Luo, K., Derrick, M., Yu, L., Quinlan, K. A., Vasquez-Vivar, J., Nogueira, M. I., & Tan, S. (2015). Elevated spinal monoamine neurotransmitters after antenatal hypoxia-ischemia in rabbit cerebral palsy model. Journal of neurochemistry, 132(4), 394-402. https://doi.org/10.1111/jnc.12997