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Differential expression of serotonin 2A (5HT 2A ) receptors in the phrenic motor nucleus over disease progression in a rat model (SOD1 G93A ) of ALS
Author(s) -
Borkowski Lauren Faith,
Craig Taylor A,
Nichols Nicole L.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.873.12
Subject(s) - phrenic nerve , amyotrophic lateral sclerosis , motor neuron , medicine , endocrinology , sod1 , receptor , chemistry , neuroscience , biology , spinal cord , respiratory system , disease
Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to progressive motor neuron degeneration and, ultimately, death by ventilatory failure. In a rat model of ALS (SOD1 G93A ), phrenic long‐term facilitation (pLTF) following acute intermittent hypoxia (a form of phrenic motor facilitation and respiratory plasticity) is NADPH oxidase dependent in pre‐symptomatic rats, but NADPH oxidase independent at disease end‐stage (Nichols et al., 2015). Naïve rats express pLTF via a 5HT 2 and NADPH oxidase dependent mechanism. Furthermore, 5HT 2A , not 5HT 2B , receptor induced phrenic motor facilitation is NADPH oxidase independent in naïve rats (MacFarlane et al., 2014). Here, we tested the hypothesis that 5HT 2A receptor expression in the phrenic motor nucleus is upregulated in end‐stage SOD1 G93A rats compared to age‐matched, wild‐type littermates and pre‐symptomatic SOD1 G93A rats using immunohistochemistry. However, our preliminary data suggest that end‐stage SOD1 G93A rats have significantly less 5HT 2A positive pixels in the phrenic motor nucleus and the non‐phrenic ventral horn (40±8 and 19±4 pixels, respectively; n=9) vs . age‐matched, wild‐type littermates (72±12 and 36±6 pixels, respectively; n=8; p<0.05), and pre‐symptomatic SOD1 G93A rats (2773±474 and 1833±1556 pixels, respectively; n=3; p<0.05). 5HT 2A positive pixels in the phrenic motor nucleus and the non‐phrenic ventral horn were unaffected when comparing pre‐symptomatic SOD1 G93A rats to age‐matched, wild‐type littermates (2199±396 and 2678±1127 pixels, respectively; n=3; p>0.05). In summary, our preliminary data suggest that 5HT 2A receptor expression is decreased with age and with disease progression. Although 5HT 2A receptor expression is decreased in end‐stage SOD1 G93A rats, this does not rule out the functional upregulation of 5HT 2A receptors on surviving phrenic motor neurons or if they are required for pLTF. Future studies will be focused on: 1) completing 5HT 2A histological analysis comparing pre‐symptomatic vs. end‐stage SOD1 G93A rats; 2) determining 5HT 2B expression in SOD1 G93A rats; 3) determining if pLTF in end‐stage SOD1 G93A rats is 5HT 2A , not 5HT 2B , dependent; and 4) determining if other reactive oxygen species ( e.g. nitrogen oxygen species) that do not require NADPH oxidase compensate to exhibit pLTF in end‐stage SOD1 G93A rats. This project increases our understanding of the expression of receptors associated with respiratory plasticity and its implications for breathing in motor neuron disease. Support or Funding Information Supported by NIH K99/R00 HL119606