Vol 76, No 1 (2017)
Original article
Published online: 2016-07-04
Adrenal medulla of AS/AGU rats: a histological and immunohistochemical study
Abstract
Background: The outcome of the autograft therapy for Parkinson’s disease including autologous cells from adrenal medulla was disappointing. This could be attributed to the pathological process in Parkinson’s disease affecting cells of the adrenal medulla. This study was performed to investigate the histopathological changes in the adrenal medulla of AS/AGU rat, a model of Parkinson’s disease, in comparison with Albino Swiss (AS) rats.
Materials and methods: A total of 24 male AS rats were divided into four groups, each of 6 animals: AS W1 — AS rats aged 1 week; AS adult — AS adult rats; AS/ /AGU W1 — AS/AGU rats aged 1 week; and AS/AGU adult — AS/AGU adult rats. The rats were sacrificed and the adrenal glands were dissected and processed for histological staining with haematoxylin and eosin and periodic acid Schiff and for immunohistochemical staining for S100 protein, ubiquitin and tyrosine hydroxylase.
Results: The histological investigation of the adrenal medulla of AS/AGU rats showed vascular congestion, inflammatory cellular infiltration, pyknotic nuclei, necrotic chromaffin cells and medullary inclusion bodies. The immunohistochemical investigation of AS/AGU rats showed a statistically significant decrease in the expression of S100 protein, ubiquitin and tyrosine hydroxylase compared to AS rats.
Conclusions: The histological and immunohistological changes in the adrenal medulla could explain the failure of outcome of adrenal autograft therapy in Parkinson’s disease.
Keywords: AS ratsAS/AGU ratsParkinson’s diseaseadrenal medullahistologyimmunohistochemistryS100ubiquitintyrosin hydroxylase
References
- Adams JD, Jr., Chang ML, Klaidman L. Parkinson's disease--redox mechanisms. Curr Med Chem. 2001; 8(7): 809–814.
- Arrasate M, Mitra S, Schweitzer ES, et al. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature. 2004; 431(7010): 805–810.
- Barcia C. Glial-mediated inflammation underlying parkinsonism. Scientifica (Cairo). 2013; 2013: 357805.
- Beutler B, van Huffel C. Unraveling function in the TNF ligand and receptor families. Science. 1994; 264(5159): 667–668.
- Blum-Degen D, Müller T, Kuhn W, et al. Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neurosci Lett. 1995; 202(1-2): 17–20.
- Bojinov S, Guentchev T. [Acute encephalitis and myocarditis in a 4 and a half year old infant. (Acute Parkinson syndrome with regressive clinical evolution. Severe myocarditis and bilateral symmetric necrotic inflammation of the locus niger)]. Neuropatol Pol. 1966; 4: Suppl: 655–658.
- Bojinov S. Encephalitis with acute Parkinsonian syndrome and bilateral inflammatory necrosis of the substantia nigra. J Neurol Sci. 1971; 12(4): 383–415.
- Boka G, Anglade P, Wallach D, et al. Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease. Neurosci Lett. 1994; 172(1-2): 151–154.
- Campbell JM, Payne AP, Gilmore DP, et al. Neostriatal dopamine depletion and locomotor abnormalities due to the Albino Swiss rat agu mutation. Neurosci Lett. 1996; 213(3): 173–176.
- Chen-Pan C, Pan IJ, Yamamoto Y, et al. Prompt recovery of damaged adrenal medullae induced by salinomycin. Toxicol Pathol. 1999; 27(5): 563–572.
- Ciechanover A, Brundin P. The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg. Neuron. 2003; 40(2): 427–446.
- Clarke DJ, Payne AP. Neuroanatomical characterization of a new mutant rat with dopamine depletion in the substantia nigra. Eur J Neurosci. 1994; 6(5): 885–888.
- Cook HC. Manual of histological demonstration techniques. Butterworth-Heinemann, 1974.
- Coppola D, Fu L, Nicosia SV, et al. Prognostic significance of p53, bcl-2, vimentin, and S100 protein-positive Langerhans cells in endometrial carcinoma. Hum Pathol. 1998; 29(5): 455–462.
- Coux O, Tanaka K, Goldberg AL. Structure and functions of the 20S and 26S proteasomes. Ann Rev Biochem. 1996; 65: 801–847.
- Craig NJ, Durán Alonso MB, Hawker KL, et al. A candidate gene for human neurodegenerative disorders: a rat PKC gamma mutation causes a Parkinsonian syndrome. Nat Neurosci. 2001; 4(11): 1061–1062.
- Drury R, Wallington E. Preparation and fixation of tissues. In: Drury R, Wallington E eds. Carleton's histological technique. 5th Ed. Oxford University Press, Oxford, 1980; pp. 41–54.
- Dunnett SB, Björklund A. Prospects for new restorative and neuroprotective treatments in Parkinson's disease. Nature. 1999; 399(6738 Suppl): A32–A39.
- Fitzpatrick KM, Raschke J, Emborg ME. Cell-based therapies for Parkinson's disease: past, present, and future. Antioxid Redox Signal. 2009; 11(9): 2189–2208.
- Flatmark T, Almas B, Ziegler MG. Catecholamine metabolism: an update on key biosynthetic enzymes and vesicular monoamine transporters. Ann NY Acad Sci. 2002; 971: 69–75.
- Hawlitschka A, Haas SJP, Schmitt O, et al. Effects of systemic PSI administration on catecholaminergic cells in the brain, adrenal medulla and carotid body in Wistar rats. Brain Res. 2007; 1173: 137–144.
- Haycock JW, Wakade AR. Activation and multiple-site phosphorylation of tyrosine hydroxylase in perfused rat adrenal glands. J Neurochem. 1992; 58(1): 57–64.
- Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998; 67: 425–479.
- Himeda T, Watanabe Y, Tounai H, et al. Time dependent alterations of co-localization of S100beta and GFAP in the MPTP-treated mice. J Neural Transm (Vienna). 2006; 113(12): 1887–1894.
- Hurtig H, Joyce J, Sladek JR, et al. Postmortem analysis of adrenal-medulla-to-caudate autograft in a patient with Parkinson's disease. Ann Neurol. 1989; 25(6): 607–614.
- Kelly PJ, Ahlskog JE, van Heerden JA, et al. Adrenal medullary autograft transplantation into the striatum of patients with Parkinson's disease. Mayo Clin Proc. 1989; 64(3): 282–290.
- Kompoliti K, Chu Y, Shannon KM, et al. Neuropathological study 16 years after autologous adrenal medullary transplantation in a Parkinson's disease patient. Mov Disord. 2007; 22(11): 1630–1633.
- Kordower JH, Cochran E, Penn RD, et al. Putative chromaffin cell survival and enhanced host-derived TH-fiber innervation following a functional adrenal medulla autograft for Parkinson's disease. Ann Neurol. 1991; 29(4): 405–412.
- Larrick JW, Wright SC. Cytotoxic mechanism of tumor necrosis factor-alpha. FASEB J. 1990; 4(14): 3215–3223.
- Madrazo I, Drucker-Colín R, Díaz V, et al. Open microsurgical autograft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson's disease. N Engl J Med. 1987; 316(14): 831–834.
- McNaught KS, Mytilineou C, Jnobaptiste R, et al. Impairment of the ubiquitin-proteasome system causes dopaminergic cell death and inclusion body formation in ventral mesencephalic cultures. J Neurochem. 2002; 81(2): 301–306.
- Mogi M, Harada M, Riederer P, et al. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett. 1994; 165(1-2): 208–210.
- Mogi M, Harada M, Narabayashi H, et al. Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease. Neurosci Lett. 1996; 211(1): 13–16.
- Müller T. Drug therapy in patients with Parkinson's disease. Transl Neurodegener. 2012; 1(1): 10.
- Muramatsu Y, Kurosaki R, Watanabe H, et al. Expression of S-100 protein is related to neuronal damage in MPTP-treated mice. Glia. 2003; 42(3): 307–313.
- Payne AP, Sutcliffe RG, Campbell JM, et al. Disordered locomotion in the AS/AGU mutant rat and the effects of L-dopa or fetal midbrain grafts. Mov Disord. 1998; 13(5): 832–834.
- Payne AP, Campbell JM, Russell D, et al. The AS/AGU rat: a spontaneous model of disruption and degeneration in the nigrostriatal dopaminergic system. J Anat. 2000; 196 (Pt 4): 629–633.
- Riederer P, Rausch WD, Birkmayer W, et al. CNS Modulation of adrenal tyrosine hydroxylase in Parkinson's disease and metabolic encephalopathies. J Neural Transm Suppl. 1978(14): 121–131.
- Rodriguez H, Filippa V, Mohamed F, et al. Interaction between chromaffin and sustentacular cells in adrenal medulla of viscacha (Lagostomus maximus maximus). Anat Histol Embryol. 2007; 36(3): 182–185.
- Sherman MY, Goldberg AL. Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron. 2001; 29(1): 15–32.
- Shinzato M, Shamoto M, Hosokawa S, et al. Differentiation of Langerhans cells from interdigitating cells using CD1a and S-100 protein antibodies. Biotech Histochem. 1995; 70(3): 114–118.
- Stoddard SL. The adrenal medulla and Parkinson's disease. Rev Neurosci. 1994; 5(4): 293–307.
- Stypuła G, Kunert-Radek J, Stepień H, et al. Evaluation of interleukins, ACTH, cortisol and prolactin concentrations in the blood of patients with parkinson's disease. Neuroimmunomodulation. 1996; 3(2-3): 131–134.
- Sugie M, Goto J, Kawamura M, et al. Increased norepinephrine-associated adrenomedullary inclusions in Parkinson's disease. Pathol. Int. 2005; 55(3): 130–136.
- Wijeyekoon R, Barker RA. Cell replacement therapy for Parkinson's disease. Biochim Biophys Acta. 2009; 1792(7): 688–702.
- Wilson AJ, Maddox PH, Jenkins D. CD1a and S100 antigen expression in skin Langerhans cells in patients with breast cancer. J Pathol. 1991; 163(1): 25–30.
- Young J. Catecholamines and the adrenal medulla. Pheochromocytoma. In: Wilson J, Foster D, Kronenberg H, Larson P eds. Williams Textbook of Endocrinology, 1998; pp. 705–728.
