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Acute Lung Injury Alters AMPA Receptor Subunit Density in the Dorsal Vagal Complex
Author(s) -
Litvin David Gregory,
Dick Thomas E,
Jacono Frank J
Publication year - 2016
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.30.1_supplement.988.10
Subject(s) - ampa receptor , dorsal motor nucleus , brainstem , glutamatergic , nucleus ambiguus , medicine , glutamate receptor , neuroscience , solitary nucleus , neurotransmission , nucleus , chemistry , endocrinology , medulla oblongata , anesthesia , vagus nerve , receptor , central nervous system , biology , stimulation
Ventilatory pattern is a neurally integrated output that is altered by lung injury. Work in our lab has provided evidence that acute lung injury (ALI) promotes changes in ventilatory pattern, which persist in situ and are associated with synaptic plasticity at 2 nd order nucleus tractus solitarii (nTS) neurons. Therefore, in the current study, we sought to identify evidence that brainstem autonomic circuits were undergoing changes in glutamatergic transmission following ALI. We hypothesized that ALI could be promoting changes in brainstem α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor subunits. To test this hypothesis, we intratrachially instilled bleomycin (Bleo) in postnatal (P) 11 Sprague Dawley rats and sacrificed them at P18 for fluorescent immunostaining of the AMPA‐R subunits GluR1, GluR2, and GluR4, followed by confocal microscopy and densitometric analysis. AMPA‐R subunit immunoreactivity was measured in the nTS, dorsal motor nucleus of the vagus (DMNX), and hypoglossal nucleus (XII). Significant increases in GluR2 immunoreactive density were observed in the nTS of Bleo (0.185±0.036AU n=5) versus PBS (0.108±0.035AU p =0.02, n=5) rats. There were no significant differences in GluR1 ( p =0.31) or GluR4 ( p =0.70) immunoreactive density in the nTS. In the DMNX, there were significant increases in GluR1 (Bleo: 0.071±0.017AU vs. PBS: 0.0496±0.01AU, p =0.047) and GluR2 (Bleo: 0.057±0.016AU vs. PBS: 0.028±0.0134AU, p= 0.03) immunoreactivity. There was a significant decrease in GluR4 density in the DMNX (Bleo: 0.238±0.023AU vs. PBS: 0.295±0.025AU, p =0.02). Finally, there were no significant changes in GluR1 ( p =0.209), GluR2 ( p =0.275), and GluR4 ( p =0.103) in the XII. Taken together, these results show that bleo induced lung injury promotes changes in the density of AMPA‐R subunits in the dorsal vagal complex. These findings suggest that altered glutamatergic transmission in the dorsal vagal complex may contribute to synaptic plasticity and ventilatory pattern changes in the setting of lung injury. Support or Funding Information VA Research Service Award Number I01BX000873 and NIH T32HL007913