Alpha-synuclein pathology in the medulla oblongata in association with the reduction of the ventilatory response to hypercapnia in dementia with Lewy bodies and Parkinson's disease

Abstract

We have previously reported the reduction of the ventilatory response to hypercapnia (VRH), which reflects an autonomic nervous function, in 100% of patients with dementia with Lewy bodies (DLB) examined. Other groups reported the reduction of VRH in approximately 50% of patients with Parkinson's disease (PD). These results suggest that the reduction of VRH may be a useful diagnostic marker for DLB and PD, although the pathological changes underlying it are unknown. To elucidate these issues, in the present study, we immunohistochemically examined the appearance of alpha-synuclein positive structures in the raphe nuclei, the solitary nucleus and the ventrolateral medulla (VLM) of the medulla oblongata, which is thought to be the center of the ventilatory response, in 12 cases of DLB and 9 cases of PD, using the phosphorylation specific antibody to alpha-synuclein. The results showed that a number of alpha-synuclein positve structures, including Lewy bodies, Lewy neurites and Lew dots, were found in the raphe nuclei, the solitary nucleus and the VLM in both DLB and PD cases. Comparing the number of the alpha-synuclein positive structures between DLB and PD in these nuclei, that of Lewy bodies in the raphe nuclei tended to be larger in the DLB cases than in the PD cases. Previous report indicated that the number of neuron in the raphe nuclei was significantly smaller in the DLB cases than in the PD cases. These results suggest that neuronal dysfunction due to accumulation of alpha-synuclein in the raphe nuclei may be associated with the reduction of VRH, which might explain the higher rate of the VRH reduction in DLB than in PD.