5-HT2A/B receptor expression in the phrenic motor nucleus in a rat model of ALS (SOD1G93A)

Respir Physiol Neurobiol. 2020 Aug:279:103471. doi: 10.1016/j.resp.2020.103471. Epub 2020 Jun 3.

Abstract

Despite respiratory motor neuron death, ventilation is preserved in SOD1G93A rats. Compensatory respiratory plasticity may counterbalance the loss of these neurons. Phrenic long-term facilitation (pLTF; a form of respiratory plasticity) in naïve rats is 5-HT2 and NADPH oxidase-dependent. Furthermore, 5-HT2A, not 5-HT2B, receptor-induced phrenic motor facilitation is NADPH oxidase-independent in naïve rats. pLTF is NADPH oxidase-dependent in pre-symptomatic, but not end-stage, SOD1G93A rats. Here, we hypothesized that in the putative phrenic motor nucleus (PMN) of SOD1G93A rats vs. wild-type littermates: 1) pre-symptomatic rats would have greater 5-HT2B receptor expression that decreases at end-stage; and 2) 5-HT2A receptor expression would increase from pre-symptomatic to end-stage. Putative PMN 5-HT2A receptor expression was reduced when comparing across (but not within) pre-symptomatic vs. end-stage groups (p < 0.05). In contrast, putative PMN 5-HT2B receptor expression was increased when comparing across pre-symptomatic vs. end-stage groups, and within end-stage groups (p < 0.05). These data suggest a potential role for 5-HT2 receptors in pLTF and breathing in SOD1G93A rats.

Keywords: Amyotrophic lateral sclerosis; Breathing; Plasticity; Respiratory motor neuron; Serotonin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Anterior Horn Cells / metabolism*
  • Asymptomatic Diseases
  • Cervical Vertebrae
  • Diaphragm / innervation*
  • Disease Models, Animal
  • Disease Progression
  • Long-Term Potentiation
  • Neuronal Plasticity
  • Phrenic Nerve*
  • Rats
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Receptor, Serotonin, 5-HT2B / metabolism*
  • Superoxide Dismutase-1 / genetics

Substances

  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2B
  • Superoxide Dismutase-1