Serotonergic immunoreactivity in the brainstem and spinal cord of mdx mice

Abstract

The mdx mouse model of Duchenne muscular dystrophy exhibits profound respiratory muscle weakness and muscle fiber remodeling. Initial studies of respiratory control in mdx mice indicate increased respiratory motor output during respiratory challenge, possibly indicating a compensatory neuroplastic response of the respiratory neural control system in the face of muscle pathology (Burns et al., J Physiol, 2017). Serotonin plays a fundamental role in the induction of respiratory neuroplasticity, and in ongoing experiments we are testing the hypothesis that mdx mice have a compensatory increase in serotonergic innervation of the brainstem and spinal cord. The cervical (C4) and thoracic (T4) spinal cord and medulla of three‐month‐old wild type and mdx mice were harvested and incubated with antibodies to recognize serotonin and choline acetyltransferase (ChAT) to identify motoneurons. The intensity of serotonergic immunostaining was quantified in an unbiased manner using a custom Matlab code. In the cervical spinal cord, serotonergic immunostaining was prominent in the ventral horn (lamina 9). The thoracic cord also showed serotonergic immunoreactivity in the aforementioned region, but staining was most prominent in the lateral horn (intermediolateral nucleus). There was no indication of differences in spinal serotonergic staining between control and mdx mice. In contrast, the mdx mice showed a clear trend toward increased serotonin staining in caudal medullary regions important for cardiovascular and respiratory control, including the nucleus ambiguous, hypoglossal motor nucleus, and the dorsal motor nucleus of the vagus. These preliminary findings support the hypothesis that serotonergic neurons undergo neuroplastic changes in mdx mice, and this may have implications for respiratory motor control.Support or Funding InformationT32‐HL134621‐01A1 (LBW), T32‐HD043730 (MDS), SPARC OT2 OD023854 (DDF), 1 R01 NS080180‐01A1 (DDF)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.