Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibo...Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibody has been revealed to impair fast excitatory synaptic transmission in autonomic ganglia, its precise mechanism remains unknown. Here, we show that antibody-induced reduction of cell-surface α3 subunits result in impairment of nicotine-evoked Ca2+ influx in stably transfected human embryonic kidney cells. These effects of the antibody were remarkably inhibited by interfering with the endocytic machinery at low-temperature. We conclude that reduction of nAChR in autonomic ganglia can be mediated by the endocytosis of α3 subunits, and resulted in autonomic failure in AAG patients.展开更多
As an environmental risk factor, psychological stress may trigger the onset or accelerate the progression of Parkinson＇s disease （PD）. Here, we evaluated the effects of acute restraint stress on striatal dopaminerg...As an environmental risk factor, psychological stress may trigger the onset or accelerate the progression of Parkinson＇s disease （PD）. Here, we evaluated the effects of acute restraint stress on striatal dopaminergic terminals and the brain metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahy- dropyridine （MPTP）, which has been widely used for creating a mouse model of PD. Exposure to 2 h of restraint stress immediately after injection of a low dose of MPTP caused a severe loss of striatal dopaminergic terminals as indicated by decreases in the dopamine transporter protein and dopamine levels compared with MPTP administration alone. Both striatal 1-methyl-4-phenylpyridinium ion （MPP＋） and MPTP concentrations were significantly increased by the application of restraint stress. Striatal monoamine oxidase-B, which catalyzes the oxidation of MPTP to MPP＋, was not changed by the restraint stress. Our results indicate that the enhanced striatal dopaminergic terminal loss in the stressed mice is associated with an increase in the transport of neurotoxin into the brain.展开更多
文摘Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibody has been revealed to impair fast excitatory synaptic transmission in autonomic ganglia, its precise mechanism remains unknown. Here, we show that antibody-induced reduction of cell-surface α3 subunits result in impairment of nicotine-evoked Ca2+ influx in stably transfected human embryonic kidney cells. These effects of the antibody were remarkably inhibited by interfering with the endocytic machinery at low-temperature. We conclude that reduction of nAChR in autonomic ganglia can be mediated by the endocytosis of α3 subunits, and resulted in autonomic failure in AAG patients.
基金supported by the Specific Research Foundation of Hokuriku University(250100)
文摘As an environmental risk factor, psychological stress may trigger the onset or accelerate the progression of Parkinson＇s disease （PD）. Here, we evaluated the effects of acute restraint stress on striatal dopaminergic terminals and the brain metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahy- dropyridine （MPTP）, which has been widely used for creating a mouse model of PD. Exposure to 2 h of restraint stress immediately after injection of a low dose of MPTP caused a severe loss of striatal dopaminergic terminals as indicated by decreases in the dopamine transporter protein and dopamine levels compared with MPTP administration alone. Both striatal 1-methyl-4-phenylpyridinium ion （MPP＋） and MPTP concentrations were significantly increased by the application of restraint stress. Striatal monoamine oxidase-B, which catalyzes the oxidation of MPTP to MPP＋, was not changed by the restraint stress. Our results indicate that the enhanced striatal dopaminergic terminal loss in the stressed mice is associated with an increase in the transport of neurotoxin into the brain.
