Neither serotonin nor adenosine-dependent mechanisms preserve ventilatory capacity in ALS rats

作者：Nichols N L; Johnson R A; Satriotomo I; Mitchell G S^*

来源：Respiratory Physiology & Neurobiology, 2014, 197: 19-28.

DOI：10.1016/j.resp.2014.03.005

• Plethysmography
• Compensatory plasticity
• Respiration
• Facilitation

In rats over-expressing SOD1(G93A), ventilation is preserved despite significant loss of respiratory motor neurons. Thus, unknown forms of compensatory respiratory plasticity may offset respiratory motor neuron cell death. Although mechanisms of such compensation are unknown, other models of respiratory motor plasticity may provide a conceptual guide. Multiple cellular mechanisms give rise to phrenic motor facilitation; one mechanism requires spinal serotonin receptor and NADPH oxidase activity whereas another requires spinal adenosine receptor activation. Here, we studied whether these mechanisms contribute to compensatory respiratory plasticity in SOD1(G93A) rats. Using plethysmography, we assessed ventilation in end-stage SOD1(G93A) rats after: (1) serotonin depletion with parachlorophenylalanine (PCPA), (2) serotonin (methysergide) and A2A (MSX-3) receptor inhibition, (3) NADPH oxidase inhibition (apocynin), and (4) combined treatments. The ability to increase ventilation was not decreased by individual or combined treatments; thus, these mechanisms do not maintain breathing capacity at end-stage motor neuron disease. Possible mechanisms giving rise to enhanced breathing capacity with combined treatment in end-stage SOD1(G93A) rats are discussed.

• 出版日期2014-6-15