WJNS  Vol.2 No.3 , August 2012
Tyrosine hydroxylase and Lewy body molecules immunoreactivity in the SNC neurons of an AS/AGU mutantrat
ABSTRACT
The AS/AGU rat has a recessive single point mutation in the gene coding for the gamma isoform of protein kinase C (PKC-γ) resulting in a failure to release dopamine in the striatum and impaired movement including a staggering gait, difficulty in initiating movement and a slight whole body tremor. This study examined the levels tyrosine hydroxylase, ubiquitin and parkin in individual SNC cell bodies, there was no evidence of a reduction in tyrosine hydroxylase levels although levels of ubiquitin and parkin were elevated in the cytoplasm. The findings support the hypothesis that the initial bar to dopamine availability in the striatum is reduced release, with substantia nigra cell death being a later phenomenon.

Cite this paper
Al-Kushi, A. , Russell, D. and Payne, A. (2012) Tyrosine hydroxylase and Lewy body molecules immunoreactivity in the SNC neurons of an AS/AGU mutantrat. World Journal of Neuroscience, 2, 150-155. doi: 10.4236/wjns.2012.23023.
References
[1]   Craig, N.J., Alonso, M.B.D., Hawker, K.L., Shiels, P., Glencorse, T.A., Campbell, J.M., Bennett, N.K., Canham, M., Donald, D., Gardiner, M., Gilmore, D.P., MacDonald, R.J., Maitland, K., McCallion, A.S., Russell, D., Payne, A.P., Sutcliffe, R.G. and Davies, R.W. (2001) A candidate gene for human neurodegenerative disorders: A rat PKC gamma mutation causes a Parkinsonian syndrome. Nature Neuroscience, 4, 1061-1062. doi:10.1038/nn740

[2]   Clarke, D.J. and Payne, A.P. (1994) Neuroanatomical characterization of a new mutant rat with dopamine depletion in the substantia nigra. European Journal of Neuroscience, 6, 885-888. doi:10.1038/nn740

[3]   Payne, A.P., Sutcliffe, R.G., Campbell, J.M., Favor, G., Russell, D., Bennett, N.K., Clarke, D.J., Branton, R., Davies, R.W., Simpson, E., Tsang, C. and Baxendale, R.H. (1998) Disordered locomotion in the AS/AGU mutant rat and the effects of L-DOPA or fetal midbrain grafts. Movement Disorders, 13, 832-834. doi:10.1002/mds.870130514

[4]   Campbell, J.M., Gilmore, D.P., Russell, D., Growney, C.A., Favor, G., Weir, J., Stone, T.W. and Payne, A.P. (1998) Extracellular levels of dopamine and its metabolite 3,4-dihydroxy-phenylacetic acid measured by microdialysis in the corpus striatum of conscious AS/AGU mutant rats. Neuroscience, 85, 323-325. doi:10.1016/S0306-4522(98)00053-0

[5]   Al-Fayez, M., Russell, D., Davies, R.W., Shiels, P., Baker, P.J. and Payne, A.P. (2005) Deficits in the midbrain raphe nuclei and striatum of the AS/AGU rat: A protein kinase C-g mutant. European Journal of Neuroscience, 22, 2792-2798. doi:10.1111/j.1460-9568.2005.04502.x

[6]   Lam, A.G., Campbell, J.M., Bennett, N.K., Payne, A.P., Davies, R.W., Sutcliffe, R.G. and McCulloch, J. (1998) Local cerebral glucose utilization in the AS/AGU rat: A mutant with movement disorders. European Journal of Neuroscience, 10, 1963-1967. doi:10.1046/j.1460-9568.1998.00206.x

[7]   Payne, A.P., Campbell, J.M., Russell, D., Favor, G., Sutcliffe, R.G., Bennett, N.K., Davies, R.W. and Stone, T.W. (2000) The AS/AGU rat: A spontaneous model of disruption and degeneration in the nigrostriatal dopaminergic system. Journal of Anatomy, 196, 629-633. doi:10.1046/j.1469-7580.2000.19640629.x

[8]   Choi, W.S., Yoon, S.Y., Oh, T.H., Choi, E.J., O’Malley, K.L. and Oh, Y.J. (1999) Two distinct mechanisms are involved in 6-hydroxydopamine- and MPP+-induced dopaminergic neuronal cell death: Role of caspases, ROS, and JNK. Journal of Neuroscience Research, 57, 86-94. doi:10.1002/(SICI)1097-4547(19990701)57:1<86::AID-JNR9>3.0.CO;2-E

[9]   Tatton, N.A. and Kish, S.J. (1997) In situ detection of apoptotic nuclei in the substantia nigra compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice using terminal deoxynucleotidyltransferase labelling and acridine orange staining. Neuroscience, 77, 1037-1048. doi:10.1016/S0306-4522(96)00545-3

[10]   Spooren, W.P., Gentsch, C. and Wiessner, C. (1998) TUNEL-positive cells in the substantia nigra of C57BL/6 mice after a single bolus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroscience, 85, 649-651.

[11]   Serra, P.A., Sciola, L., Delogu, M.R., Spano, A., Monaco, G., Miele, E., Rocchitta, G., Miele, M., Migheli, R. and Desole, M.S. (2002) The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induces apoptosis in mouse nigrostriatal glia: Relevance to nigral neuronal death and striatal neurochemical changes. Journal of Biological Chemistry, 277, 34451-34461. doi:10.1074/jbc.M202099200

[12]   Oztas, E. and Topal, T. (2003) A cell protective mechanism in a murine model of Parkinson’s disease. Turkish Journal of Medical Sciences, 33, 295-299.

[13]   Schwarting, R.K.W. and Huston, J.P. (1996) The unilateral 6-hydroxydopamine lesion model in behavioural brain research. Analysis of functional deficits, recovery and treatments. Progress in Neurobiology, 50, 275-331. doi:10.1016/S0301-0082(96)00040-8

[14]   Flint, B.M. (2001) Experimental models of Parkinson’s disease. Nature Reviews Neuroscience, 2, 325-332.

[15]   Forno, L.S., DeLanney, L.E., Irwin, I. and Langston, J.W. (1993) Similarities and differences between MPTP-induced parkinsonsim and Parkinson’s disease. Neuropathologic considerations. Advanced Neurology, 60, 600-608.

[16]   Dauer, W. and Przedborski, S. (2003) Parkinson’s disease: Mechanisms and models. Neuron, 39, 889-909. doi:10.1016/S0896-6273(03)00568-3

[17]   Betarbet, R., Sherer, T.B., MacKenzie, G., Garcia-Osuna, M., Panov, A.V. and Greenamyre, J.T. (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nature Neuroscience, 3, 1301-1306. doi:10.1038/81834

[18]   Paxinos, G. and Watson, C. (1982) The rat brain in stereotaxic coordinates. Academic Press, Waltham.

[19]   Shi, S.R., Key, M.E. and Kalra, K.L. (1991) Antigen retrieval in formalin-fixed, paraffin-embedded tissues: An enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. Journal of Histochemistry & Cytochemistry, 39, 741-748. doi:10.1177/39.6.1709656

[20]   Norton, A.J., Jordan, S. and Yeomans, P. (1994) Brief, high-temperature heat denaturation (pressure cooking): A simple and effective method of antigen retrieval for routinely processed tissues. The Journal of Pathology, 173, 371-379. doi:10.1002/path.1711730413

[21]   Muqit, M.M.K., Davidson, S.M., Smith, M.D.P., MacCormac, L.P., Kahns, S., Jensen, P.H., Wood, N.W. and Latchman, D.S. (2004) Parkin is recruited into aggresomes in a stress-specific manner: Over-expression of parkin reduces aggresome formation but can be dissociated from parkin’s effect on neuronal survival. Human Molecular Genetics, 13, 117-135. doi:10.1093/hmg/ddh012

[22]   Campbell, J. M., Payne, A.P., Gilmore, D.P., Byrne, J.E., Russell, D., McGadey, J., Clarke, D.J., Branton, R., Davies, R.W. and Sutcliffe, R.G. (1997) Age changes in dopamine levels in the corpus striatum of Albino Swiss (AS) and AS/AGU mutant rats. Neuroscience Letters, 239, 54-56. doi:10.1016/S0304-3940(97)00871-9

[23]   Campbell, J.M., Payne, A.P., Gilmore, D.P., Byrne, J.E., Russell, D., McGadey, J., Clarke, D.J., Davies, R.W. and Sutcliffe, R.G. (1996) Neostriatal dopamine depletion and locomotor abnormalities due to the Albino Swiss rat agu mutation. Neuroscience Letters, 213, 173-176.

[24]   Roffler-Tarlov, S. and Graybiel, A.M. (1984) Weaver mutation has differential effects on the dopamine-containing innervation of the limbic and non-limbic striatum. Nature, 307, 62-66. doi:10.1038/307062a0

[25]   Hornykiewicz, O. (1995) Striatal dopamine in dopa-responsive dystonia: Comparison with idiopathic Parkinson’s disease and other dopamine-dependent disorders. In: Segawa, M. and Nomura, Y., Ed., Age-Related Dopamine-Dependent Disorders, Karger, Basel, 101-108

[26]   Leenders, K.L., Palmer, A.J., Quinn, N., Clark, J.C., Firnau, G., Garnett, E.S., Nahmias, C., Jones, T. and Marsden, C.D. (1986) Brain dopamine metabolism in patients with Parkinson’s disease measured with positron emission tomography. Journal of Neurology, Neurosurgery & Psychiatry, 49, 853-860. doi:10.1136/jnnp.49.8.853

[27]   Leenders, K.L., Salmon, E.P., Tyrrell, P., Perani, D., Brooks, D.J., Sager, H., Jones, T., Marsden, C.D. and Frackowiak, R.S. (1990) The nigrostriatal dopaminergic system assessed in vivo by positron emission tomography in healthy volunteer subjects and patients with Parkinson’s disease. Archives of Neurology, 47, 1290-1298. doi:10.1001/archneur.1990.00530120034007

[28]   Moratalla, R., Quinn, B., DeLanney, L.E., Irwin, I., Langston, J.W. and Graybiel, A.M. (1992) Differential vulnerability of primate caudate-putamen and striosome-matrix dopamine systems to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proceedings of the National Academy of Sciences of USA, 89, 3859-3863. doi:10.1073/pnas.89.9.3859

[29]   Snow, B.J., Vingerhoets, F.J., Langston, J.W., Tetrud, J.W., Sossi, V. and Calne, D.B. (2000) Pattern of dopaminergic loss in the striatum of humans with MPTP induced parkinsonism. Journal of Neurology, Neurosurgery & Psychiatry, 68, 313-316.

[30]   Lennox G., Lowe J., Morrell K., Landon M., and Mayer R.J. (1989) Anti-ubiquitin immunocytochemistry is more sensitive than conventional techniques in the detection of diffuse Lewy body disease. Journal of Neurology, Neurosurgery & Psychiatry, 52, 67-71. doi:10.1136/jnnp.68.3.313

[31]   Love, S. and Nicoll, J.A. (1992) Comparison of modified Bielschowsky silver impregnation and anti-ubiquitin immunostaining of cortical and nigral Lewy bodies. Neuropathology and Applied Neurobiology, 18, 585-592. doi:10.1111/j.1365-2990.1992.tb00830.x

[32]   Spillantini, M.G., Crowther, R.A., Jakes, R., Cairns, N.J., Lantos, P.L. and Goedert, M. (1998) Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson’s disease and dementia with Lewy bodies. Neuroscience Letters, 251, 205-208. doi:10.1016/S0304-3940(98)00504-7

[33]   Irizarry, M.C., Growdon, W., Gomez-Isla, T., Newell, K., George, J.M., Clayton, D.F. and Hyman, B.T. (1998) Nigral and cortical Lewy bodies and dystrophic nigralneurites in Parkinson’s disease and cortical Lewy body disease contain alpha-synuclein immunoreactivity. Journal of Neuropathology & Experimental Neurology, 57, 334-337. doi:10.1097/00005072-199804000-00005

[34]   Shimura, H., Hattori, N., Kubo, S., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T. and Tanaka, K. (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nature Genetics, 25, 302-305. doi:10.1038/77060

[35]   Sherman, M.Y. and Goldberg, A.L. (2001) Cellular defenses against unfolded proteins: A cell biologist thinks about neurodegenerative diseases. Neuron, 29, 15-32. doi:10.1016/S0896-6273(01)00177-5

[36]   Cookson, M.R. (2005) The biochemistry of Parkinson’s disease. Annual Review of Biochemistry, 74, 29-52. doi:10.1146/annurev.biochem.74.082803.133400

[37]   Gai, W.P., Yuan, H.X., Li, X.Q., Power, J.T., Blumbergs, P.C. and Jensen, P.H. (2000) In situ and in vitro study of colocalization and segregation of alpha-synuclein, ubiquitin, and lipids in Lewy bodies. Experimental Neurology, 166, 324-333. doi:10.1006/exnr.2000.7527

[38]   McNaught, K.S., Shashidharan, P., Perl, D.P., Jenner, P., and Olanow, C.W. (2002) Aggresome-related biogenesis of Lewy bodies. European Journal of Neuroscience, 16, 2136-2148. doi:10.1046/j.1460-9568.2002.02301.x

[39]   Moreno-Gonzalez, I and Soto, C. (2011) Misfolded protein aggregates: Mechanisms, structures and potential for disease transmission. Seminars in Cell & Developmental Biology, 22, 482-487. doi:10.1016/j.semcdb.2011.04.002

[40]   McNaught, K.S., Perl, D.P., Brownell, A.L. and Olanow, C.W. (2004) Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson’s disease. Annals of Neurology, 56, 149-162. doi:10.1002/ana.20186

[41]   Huang, Q. and Figueiredo-Pereira, M.E. (2010) Ubiquitin/ proteasome pathway impairment in neurodegeneration: Therapeutic implications. Apoptosis, 15, 1292-1311. doi:10.1007/s10495-010-0466-z

[42]   Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., and Shimizu, N. (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature, 392, 605-608. doi:10.1007/s10495-010-0466-z

[43]   Kumar, K.R., Djarmati-Westenberger, A. and Grünewald, A. (2011) Genetics of Parkinson’s disease. Seminars in Neurology, 31, 433-40. doi:10.1055/s-0031-1299782

 
 
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