Degeneration of cardiac sympathetic nerve begins in the early disease process of Parkinson's disease

Abstract

Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [(123)I] MIBG myocardial scintigraphy has been reported in the early stages of Parkinson's disease (PD), which suggests involvement of the cardiac sympathetic nerve in the early disease process of PD. For confirmation, we immunohistochemically examined cardiac tissue, sympathetic ganglia and medulla oblongata of 20 patients with incidental Lewy body disease (ILBD), which is thought to be a presymptomatic stage of PD, and 10 control subjects, using antibodies against tyrosine hydroxylase (TH) and neurofilament (NF). Immunoreactive nerve fibers of fascicles in the epicardium were well preserved in 10 of the 20 patients with ILBD and in the control subjects. In contrast, TH-immunoreactive nerve fibers had nearly disappeared in six subjects and were moderately decreased in four of the 20 patients with ILBD. Neuronal cell loss in the dorsal vagal nucleus and the sympathetic ganglia was not detectable in any of the ILBD patients examined. These findings suggest that degeneration of the cardiac sympathetic nerve begins in the early disease process of PD and that it occurs before neuronal cell loss in the dorsal vagal nucleus.

Figure 1

Semiquantitative rating scale of tyrosine hydroxylase‐ and neurofilament‐immunoreactive nerve fibers of fascicles in the epicardium. −, absent or nearly absent (A); +, sparse (B); ++, moderate (C); +++, numerous (D). Bar = 50 µm.

Figure 2

Immunohistochemical findings of the heart tissues, sympathetic ganglia and medulla oblongata at the level of the dorsal vagal nucleus in incidental Lewy body disease (ILBD) and control subjects. In the control, tyrosine hydroxylase (TH)‐ or neurofilament (NF)‐immunoreactive nerve fibers of a fascicle in the epicardium are well preserved (A,B). No neuronal cell loss (C), abundant TH‐immunoreactive neurons (D) and no α‐synuclein‐immunoreactive Lewy neurites and Lewy bodies (E) are observed in the sympathetic ganglia. Neuronal cell loss and α‐synuclein‐immunoreactive Lewy neurites and Lewy bodies are not observed in the dorsal vagal nucleus (F). In ILBD, there are different degenerating stages of nerve fibers in the fascicles (G,H,M,N,S,T). No neuronal cell loss is noticed in the sympathetic ganglia (I,O,U). TH immunoreactivity of neurons is well preserved in 18 patients (J), and the number of TH‐immunonegative neurons is slightly increased in one patient (P) and moderately increased in one patient with ILBD (V). The severity of Lewy pathology is slight (K), moderate (Q) and severe (W) in the sympathetic ganglia, and slight (L,R) and moderate (X) in the dorsal vagal nucleus. A, B, C, D, E, F: control; G, H, I, J, K, L: case 3; M, N, O, P, Q, R: case 18; S, T, U, V, W, X: case 20; A, G, M, S: cardiac tissue/TH; B, H, N, T: cardiac tissue/NF; C, I, O, U: sympathetic ganglia (SG)/hematoxylin and eosin; D, J, P, V: SG/TH; E, K, Q, W: SG/phosphorylated α‐synuclein; F, L, R, X: dorsal vagal nucleus/phosphorylated α‐synuclein. Bar = 50 µm.

Figure 3

The nerve fascicle in the epicardium immunofluorolabeled with anti‐tyrosine hydroxylase (TH) (green) (A,D,G,J,M) and anti‐neurofilament (NF) (red) antibodies (B,E,H,K,N). C, F, I, L and O are merged images. Control (A,B,C), ILBD (case 4: D,E,F), ILBD (case 15: G,H,I), ILBD (case 19: J,K,L), ILBD (case 20: M,N,O). Numerous TH (green) (D) and NF (red) (E) double‐positive cardiac sympathetic nerves (yellow) (F) are observed in half of the patients with ILBD, similar to the findings in the control subjects shown in A, B and C. In the next stage, both TH‐ and NF‐immunoreactive nerve fibers are moderately decreased (G,H,I). TH‐immunoreactive nerve fibers are markedly decreased with relatively preserved NF‐immunoreactive nerve fibers (J,K,L). Finally, not only TH‐ but also NF‐immunoreactive nerve fibers almost entirely disappeared in one patient with ILBD (M,N,O). Bar = 50 µm.