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Serotonin depletion near end‐stage disease does not impair ventilation in a rat model of amyotrophic lateral sclerosis (ALS)
Author(s) -
Nichols Nicole L.,
Johnson Rebecca A.,
Nashold Lisa J.,
Mitchell Gordon S.
Publication year - 2009
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.23.1_supplement.784.8
Subject(s) - amyotrophic lateral sclerosis , ventilation (architecture) , sod1 , endocrinology , medicine , serotonin , anesthesia , biology , disease , receptor , mechanical engineering , engineering
In rodent models of ALS (SOD1 G93A rat), ventilation is maintained until late in disease progression, despite a paucity of surviving respiratory motor neurons. Thus, surviving motor neurons compensate for motor neuron loss and preserve ventilation. We tested the hypothesis that 5‐HT is necessary for such compensatory plasticity by measuring ventilatory capacity following 5‐HT depletion near disease end stage in SOD1 G93A rats. When SOD1 G93A rats decreased body mass 15%, mutants (and wild type litter mates) were given para‐chlorophenylalanine (PCPA; 300 mg/kg IP) or vehicle injections (0.9% NaCl, 7.5 ml/kg IP) for 2 days. Ventilatory measurements were made during baseline, hypoxic (10.5% O 2 ), hypercapnic (7% CO 2 ) and hypoxic/hypercapnic (10.5% O 2 /7% CO 2 ) conditions via whole‐body plethysmography (n=3‐5 per group). PCPA had no effect (or actually increased) minute ventilation and tidal volume in all conditions studied in both mutant and wild type rats. PCPA decreased breathing frequency (f) in wild type rats; although f was lower in untreated mutant rats (vs wild type), PCPA had no additional effect. Our data provide no evidence that 5‐HT depletion impairs the capacity to increase ventilation in end‐stage SOD1 G93A rats. However, we cannot rule out a role for 5‐HT in the induction (vs maintenance) of compensatory plasticity in SOD1 G93A rats. [Supported by NIH NSO57778.]