Histochemistry of Adrenal Bodies in Parkinson's Disease

Abstract

AmsterdamI N 1912, Lewy1 described cytoplasmic hyaline inclusions in the substantia innominata and the dorsal vagal nucleus in paralysis agitans. Tr\l=e'\tiakoff2 described these inclusion bodies in the substantia nigra. In a previous paper3 I discussed the significance attached by various authors to these Lewy bodies, demonstrating additionally by a lipid-histochemical study that these Lewy bodies contain sphingomyelin. The next question concerned the relationship between the partial disintegration of such structures as the substantia nigra (in Parkinson's disease) and the disturbed catecholamine metabolism in the basal nuclei on the one hand4 and sphingomyelin storage on the other hand. There is one organ in the body which is a veritable catecholamine plant: the medulla of the adrenal gland. This is why an investigation was made into a possible disturbance of lipid metabolism in the adrenal glands in two patients with Parkinson's disease. As a control the adrenal glands of ten patients not suffering from Parkinson's disease were examined. Material and MethodsA study was made of the substantia nigra and the adrenal glands of one 72-year-old man (ease 1) and one 65-year-old man (case 2) with Parkinson's disease. A few control sections of the substantia nigra were stained with hema-toxylin-eosin on paraffin. Likewise, a few sec¬ tions of the adrenal glands were stained with hematoxylin-eosin and Masson's trichrome stain on paraffin. Next, formaldehyde solutionfixed frozen sections and paraffin sections of the adrenal gland from patient 1 were submitted to a series of 17 lipid stains. The adrenal gland of patient 2 was stained only on paraffin sections. Five were routine stains with Sudan III, Sudan IV, oil red O, Sudan black B, and luxol-fast blue. The other 12 stains were carried out according to Adams.5 They were Nile blue sulfate, osmium tetroxide-a-naphthylamine (OTAN), sodium hydroxide-, acid hematin modified after Baker, sodium hydroxideacid hematin, gold hydroxamate, osmium tetroxide, performic acid Schiff, plasmai reaction, modified PAS, cresyl violet acetic acid, and copper rubeanic acid.The table of staining methods (Table 1) reviews these stains and the substances identi¬ fied by them. Furthermore, stainings were done on formaldehyde solution-frozen sections with a routine PAS method with and without diastase and Best's carmine staining for glycogen after Pearse.6 In addition, the adrenal glands of ten patients who had died from various diseases or accidents and who were known or considered likely not to have suffered from Parkinson's disease were examined with a modified PAS with and without chloroform methanol extrac¬ tion. ResultsSince the results obtained in the two pa¬ tients with Parkinson's disease were identi¬ cal, they can be discussed under a single heading.In the hematoxylin-eosin stained control sections of the substantia nigra, Lewy bodies

Neuronal vulnerability, pathogenesis, and Parkinson's disease

“…Although they are not considered neurons, chromaffin cells of the adrenal medulla were the first cells shown to secrete catecholamines (hence, the term adrenaline ). den Hartog Jager found that PD patients display large inclusion bodies in these cells, which he called “adrenal bodies.” LP was subsequently described as present in adrenal neurons . However, later work indicated that adrenal chromaffin cells themselves did not show LP, and the adrenal bodies described by den Jager were not immunoreactive for SYN .…”

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“…The adrenal gland is evolutionarily related to the sympathetic ganglia, and its capsula contains autonomic nerves and ganglia. There is evidence of involvement of the peripheral ANS in the adrenal gland in PD 89–91. One group reported adrenomedullary inclusions (adrenal bodies) in some patients, which they recognized to be Lewy‐body‐related (though they were also associated with other neurological diseases) 92.…”

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“…It was already known that PAS-reactive adrenomedullary inclusions are mainly located on the medulla side of the corticomedullary border, and are unevenly distributed in the adrenal medulla. 7 Therefore, the number of adrenomedullary inclusions per unit area of the adrenal medulla was calculated for each autopsy patient as follows: (i) we counted the PAS-reactive adrenomedullary inclusions in the relevant adrenal section; (ii) we measured the sectional area of the adrenal medulla, which is immunoreactive to chromogranin A; and (iii) the number of adrenomedullary inclusions was divided by the value of the sectional area of the adrenal medulla to calculate the number of adrenomedullary inclusions per unit area. Then Wilcoxon's rank-sum testing, a nonparametric statistic method, was applied for a patient-control study of numbers of adrenomedullary inclusions per unit area.…”

“…They have concluded that ‘hyaline globules’ are associated with chronic neural disorders. Furthermore, den Hartog Jager has observed ‘adrenal bodies’, which are spherical and eosinophilic cytoplasmic inclusion bodies, on the medulla side of the corticomedullary border in two patients with PD, whereas ‘adrenal bodies’ were absent in nine controls out of 10 7 7,8 and spectrochemically identified presence of sulfur, calcium and phosphorus 9 in both ‘adrenal bodies’ and Lewy bodies.…”

“…Furthermore, den Hartog Jager has observed 'adrenal bodies', which are spherical and eosinophilic cytoplasmic inclusion bodies, on the medulla side of the corticomedullary border in two patients with PD, whereas 'adrenal bodies' were absent in nine controls out of 10. 7 'Adrenal bodies' have also been recognized as Lewy bodyrelated inclusion bodies, because of histochemically demonstrated presence of sphingomyelin 7,8 and spectrochemically identified presence of sulfur, calcium and phosphorus 9 in both 'adrenal bodies' and Lewy bodies. However, 'adrenal bodies' have been observed in spinocerebellar degeneration with Shy-Drager syndrome 9,10 and in Alzheimer's disease, 11 as well as in PD.…”