5-HT2A/B receptor expression in the phrenic motor nucleus in a rat model of ALS (SOD1(G93A))

ALS
08/06/2020

Borkowski LF, et al. Respir Physiol Neurobiol 2020.

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.