Increased norepinephrine‐associated adrenomedullary inclusions in Parkinson's disease

The association with Parkinson's disease (PD) of adrenomedullary inclusions, known as ‘hyaline globules’ or ‘adrenal bodies’, has been reported for over 35 years. However, the common perception has been that adrenomedullary chromaffin cells cannot be recognized as pathological cells in PD. In the present study, we discovered that the number of adrenomedullary inclusions per unit area of the adrenal medulla was larger in PD and other Lewy body disorders (LBD) than in other neurological diseases and controls without any autonomic dysfunctions, and correlated with the duration of LBD. We also showed that the cells with adrenomedullary inclusions are all norepinephrine‐secreting chromaffin cells. This was detected by PAS reaction following peroxidase immunohistochemistry of four proteins: chromogranin A, phenylethanolamine N‐methyltransferase, S‐100 protein and neurofilament protein. We also proved that the components of adrenomedullary inclusions are immunocytochemically different from those of Lewy bodies and Lewy‐related neurites, as adrenomedullary inclusions were immunonegative to ubiquitin and α‐synuclein as well as to the above four proteins. Therefore, contrary to current opinion, the norepinephrine‐secreting adrenomedullary chromaffin cell is indeed another type of pathological cell in PD and other LBD.

[1]  A. Atri,et al.  Cavernous sinus syndrome and headache due to bilateral carotid artery aneurysms. , 2003, Archives of neurology.

[2]  D. Goldstein,et al.  Plasma levels of catechols and metanephrines in neurogenic orthostatic hypotension , 2003, Neurology.

[3]  K. Wakabayashi,et al.  Sympathetic cardiac denervation in Parkinson's disease and pure autonomic failure but not in multiple system atrophy , 2002, Journal of neurology, neurosurgery, and psychiatry.

[4]  K. Wakabayashi,et al.  Different histopathology accounting for a decrease in myocardial MIBG uptake in PD and MSA , 2001, Neurology.

[5]  L. Metman,et al.  Cardiac Sympathetic Denervation in Parkinson Disease , 2000, Annals of Internal Medicine.

[6]  S. Orimo,et al.  123I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease , 1999, Journal of neurology, neurosurgery, and psychiatry.

[7]  K. Iwanaga,et al.  Lewy body–type degeneration in cardiac plexus in Parkinson’s and incidental Lewy body diseases , 1999, Neurology.

[8]  T. Krause,et al.  Impaired cardiac uptake of meta‐[123 I]iodobenzylguanidine in Parkinson's disease with autonomic failure , 1998, Acta neurologica Scandinavica.

[9]  S. Hirai,et al.  Decreased myocardial accumulation of 123I‐meta-iodobenzyl guanidine in Parkinson's disease , 1998, Nuclear medicine communications.

[10]  D. Goldstein,et al.  Sympathetic cardioneuropathy in dysautonomias. , 1997, Advances in pharmacology.

[11]  Y. Koike,et al.  A radiological analysis of heart sympathetic functions with meta-[123I]iodobenzylguanidine in neurological patients with autonomic failure. , 1994, Journal of the autonomic nervous system.

[12]  R. Coupland,et al.  Morphological aspects of chromaffin tissue: the differential fixation of adrenaline and noradrenaline. , 1993, Journal of anatomy.

[13]  T. Joh,et al.  Neuropathology of immunohistochemically identified brainstem neurons in Parkinson's disease , 1990, Annals of neurology.

[14]  R. Lloyd,et al.  Immunohistochemical localization of epinephrine, norepinephrine, catecholamine-synthesizing enzymes, and chromogranin in neuroendocrine cells and tumors. , 1986, The American journal of pathology.

[15]  F. Ikuta,et al.  Tyrosine hydroxylase protein in Lewy bodies of parkinsonian and senile brains , 1984, Journal of the Neurological Sciences.

[16]  P. Averback TWO NEW LESIONS IN ALZHEIMER'S DISEASE , 1983, The Lancet.

[17]  T. Hökfelt,et al.  Immunohistochemical studies on monoamine-containing cell systems. , 1973, Brain research.

[18]  T. Hökfelt,et al.  Immunohistochemical studies on phenylethanolamine-N-methyltransferase, dopa-decarboxylase and dopamine-β-hydroxylase , 1971, Experientia.

[19]  W. A. Jager,et al.  Histochemistry of Adrenal Bodies in Parkinson's Disease , 1970 .

[20]  W. A. Jager,et al.  Sphingomyelin in Lewy inclusion bodies in Parkinson's disease. , 1969 .

[21]  M. Hart,et al.  Hyaline globules of the adrenal medulla. , 1968, American journal of clinical pathology.

[22]  I. Benedeczky,et al.  Various Cell Types of the Adrenal Medulla , 1964, Nature.

[23]  R. Coupland,et al.  A Method for Differentiating between Noradrenaline- and Adrenaline-storing Cells in the Light and Electron Microscope , 1964, Nature.

[24]  J. Bethlem,et al.  THE DISTRIBUTION OF LEWY BODIES IN THE CENTRAL AND AUTONOMIC NERVOUS SYSTEMS IN IDIOPATHIC PARALYSIS AGITANS , 1960, Journal of neurology, neurosurgery, and psychiatry.

[25]  W. S. Monkhouse,et al.  GRAY'S ANATOMY , 1947 .

[26]  M. Utsuyama,et al.  Element analysis of lewy and adrenal bodies in Parkinson's disease by electron probe microanalysis , 2004, Acta Neuropathologica.

[27]  Hitoshi Takahashi,et al.  Parkinson's disease: an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system , 2004, Acta Neuropathologica.

[28]  A. Satoh,et al.  [Total defect of metaiodobenzylguanidine (MIBG) imaging on heart in Parkinson's disease: assessment of cardiac sympathetic denervation]. , 1997, Nihon rinsho. Japanese journal of clinical medicine.

[29]  織茂智之 Cardiac ^ I-metaiodobenzylguanidine scintigraphy in patients with Parkinson disease , 1996 .

[30]  W. A. den Jager Histochemistry of adrenal bodies in Parkinson's disease. , 1970, Archives of neurology.

[31]  W. A. den Jager Sphingomyelin in Lewy inclusion bodies in Parkinson's disease. , 1969, Archives of neurology.

[32]  N. Hillarp,et al.  Evidence of adrenaline and noradrenaline in separate adrenal medullary cells. , 1953, Acta physiologica Scandinavica.