Quantification of mRNA of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in the substantia nigra in Parkinson’s disease and schizophrenia
Abstract
Using the reverse transcription-polymerase chain reaction (RT-PCR), we developed a sensitive and quantitative method to detect all four types of human tyrosine hydroxylase (TH) mRNAs in the human brain (substantia nigra). All four types of TH mRNAs were found in the substantia nigra in the control brains examined, and the ratio of type-1, type-2, type-3, and type-4 mRNAs to the total amount of TH was 45, 52, 1.4, and 2.1%, respectively. The average amount of total TH mRNA in the normal brain (substantia nigra) was 5.5 amol of TH mRNA per microgram of total RNA. The ratios of four TH isoforms were not altered significantly in Parkinson's disease or schizophrenia. Further we measured the relative amount of aromatic L-amino acid decarboxylase (AADC) and beta-actin mRNAs in the brain samples. TH and AADC mRNAs were highly correlated in the control cases. We found that parkinsonian brains had very low levels of all four TH isoforms and AADC mRNAs in the substantia nigra compared with control brains, while no significant differences were found between schizophrenic brains and normal ones. Since the decrease in AADC mRNA was comparable to that in TH mRNA, the alteration of TH in Parkinson's disease would not be a primary event, but it would reflect the degeneration of dopaminergic neurons in the substantia nigra. This is the first reported measurement of mRNA contents of TH isoforms and AADC in Parkinson's disease and schizophrenia.
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Parkinsonian brains have very low levels of TH mRNAs in the substantia nigra compared with control brains, but no significant differences are found between schizophrenic and normal brains.
“Ichinose et al. previously showed that Parkinsonian brains had very low levels of TH mRNAs in the substantia nigra compared with control brains, but no significant differences were found between schizophrenic and normal brains [68].”
From Degradation of Tyrosine Hydroxylase by the Ubiquitin-Proteasome System in the Pathogenesis of Parkinson’s Disease and Dopa-Responsive Dystonia (2020) · cites this paper as [68]
Cites
Dopamine Receptor Binding Predicts Clinical and Pharmacological Potencies of Antischizophrenic Drugs
Creese, I., Burt, D. R., & Snyder, S. H. (1976) · Science · doi:10.1126/science.3854 · Cited by 2,220 · see citing works
Nagatsu, T., Levitt, M., & Udenfriend, S. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)93832-9 · Cited by 2,067 · see citing works
Self-citationDopamine in schizophrenia: a review and reconceptualization
Davis, K. L., Kahn, R. S., Ko, G., & Davidson, M. (1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.11.1474 · Cited by 2,021 · see citing works
Quantitation of mRNA by the polymerase chain reaction.
Wang, A. M., DOYLE, M. V., & Mark, D. F. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.24.9717 · Cited by 1,638 · see citing works
Antipsychotic drug doses and neuroleptic/dopamine receptors
SEEMAN, P., LEE, T., CHAU-WONG, M., & WONG, K. (1976) · Nature · doi:10.1038/261717a0 · Cited by 1,622 · see citing works
Levitt, M., Spector, S., Sjoerdsma, A., & Udenfriend, S. (1965) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)27006-9 · Cited by 1,023 · see citing works
Aromatic l-Amino Acid Decarboxylase
Lovenberg, W. M., Weissbach, H., & Udenfriend, S. (1962) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)81366-7 · Cited by 854 · see citing works
Nakajima‐Iijima, S., Hamada, H., Reddy, P., & Kakunaga, T. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.18.6133 · Cited by 691 · see citing works
Grima, B., Lamouroux, A., Boni, C., Julien, J., Javoy-Agid, F., & Mallet, J. J. (1987) · Nature · doi:10.1038/326707a0 · Cited by 351 · see citing works
Monoamine Mechanisms in Chronic Schizophrenia: Post-Mortem Neurochemical Findings
Crow, T. J., Baker, H. F., Cross, A. J., Joseph, M. H., Lofthouse, R., Longden, A., Owen, F., Riley, G. J., Glover, V. A. S., & Killpack, W. S. (1979) · The British Journal of Psychiatry · doi:10.1192/bjp.134.3.249 · Cited by 213 · see citing works
O’Malley, K. L., Anhalt, M., Martin, B. M., Kelsoe, J. R., Winfield, S., & Ginns, E. I. (1987) · Biochemistry · doi:10.1021/bi00396a007 · Cited by 158 · see citing works
Kaneda, N., Kobayashi, K., Ichinose, H., Kishi, F., Nakazawa, A., Kurosawa, Y., Fujita, K., & Nagatsu, T. (1987) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(87)90742-x · Cited by 157 · see citing works
Self-citationKobayashi, K., Kaneda, N., Ichinose, H., Kishi, F., Nakazawa, A., Kurosawa, Y., Fujita, K., & Nagatsu, T. (1988) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a122386 · Cited by 142 · see citing works
Self-citationKilbourne, E. J., Nankova, B. B., Lewis, E. J., et al. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42553-7 · Cited by 125 · see citing works
Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase
Ichinose, H., Kurosawa, Y., Titani, K., et al. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)91772-5 · Cited by 111 · see citing works
Self-citationFour isoforms of tyrosine hydroxylase are expressed in human brain
Lewis, D. A., Melchitzky, D. S., & Haycock, J. W. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90267-j · Cited by 92 · see citing works
Analysis of tyrosine hydroxylase and insulin transcripts in human neuroendocrine tissues
Coker, G. T., Studelska, D. R., Harmon, S., Burke, W. J., & O’Malley, K. L. (1990) · Molecular Brain Research · doi:10.1016/0169-328x(90)90052-f · Cited by 85 · see citing works
Kästner, A., Hirsch, É. C., Agid, Y., & Javoy-Agid, F. (1993) · Brain Research · doi:10.1016/0006-8993(93)91005-d · Cited by 74 · see citing works
Dopamine metabolism increases in post-mortem schizophrenic basal ganglia
Toru, M., Nishikawa, T., Mataga, N., & Takashima, M. (1982) · Journal of Neural Transmission · doi:10.1007/bf01254928 · Cited by 57 · see citing works
Nagatsu, T., & Hiroshi, I. (1991) · Comparative Biochemistry and Physiology Part C Comparative Pharmacology · doi:10.1016/0742-8413(91)90196-z · Cited by 46 · see citing works
Self-citationHaycock, J. W. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03177.x · Cited by 34 · see citing works
Increased Heterogeneity of Tyrosine Hydroxylase in Humans
Ichinose, H., Ohye, T., Fujita, K., Yoshida, M., Ueda, S., & Nagatsu, T. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.2024 · Cited by 32 · see citing works
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Results from a phase I safety trial of <i>hAADC</i> gene therapy for Parkinson disease
Eberling, J. L., Jagust, W. J., Christine, C. W., Starr, P., Larson, P., Bankiewicz, K. S., & Aminoff, M. J. (2008) · Neurology · doi:10.1212/01.wnl.0000312381.29287.ff · Cited by 370 · see citing works
Howes, O. D., Williams, M., Ibrahim, K., Leung, G., Egerton, A., McGuire, P. K., & Turkheimer, F. (2013) · Brain · doi:10.1093/brain/awt264 · Cited by 198 · see citing works
Complex molecular regulation of tyrosine hydroxylase
Tekin, I., Roskoski, R., Carkaci-Salli, N., & Vrana, K. E. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1238-7 · Cited by 128 · see citing works
Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia
Martin-Ruiz, C. M., Haroutunian, V. H., Long, P., Young, A. H., Davis, K. L., Perry, E. K., & Court, J. A. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00348-2 · Cited by 100 · see citing works
Kawahata, I., & Fukunaga, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21113779 · Cited by 71 · see citing works
- Authors
- Ichinose, H., Ohye, T., Fujita, K., Pantucek, F., Lange, K., Riederer, P., & Nagatsu, T.
- Affiliations
- Fujita Health University (JP)
- University of Würzburg (DE)
- Venue
- Journal of Neural Transmission - Parkinson's Disease and Dementia Section
- Published
- 1994-02
- Volume
- 8
- Issue
- 1-2
- Pages
- 149-158
- ISSN
- 0936-3076 (ISSN-L)
- OpenAlex
- W1972340195
- Cited by
- 107
- References
- 22
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 8 · 2021: 16 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 5 · 2014: 4 · 2013: 6 · 2012: 6
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Neural Transmission - Parkinsons Disease and Dementia Section (publishedVersion)
- PubMed (publishedVersion)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Funders
- Japan Intractable Diseases Research Foundation
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- tyrosine hydroxylase, aromatic L-amino acid decarboxylase, substantia nigra, Parkinson's disease, schizophrenia, mRNA quantification, dopaminergic neuron loss, dopamine synthesis, beta-actin
- MeSH terms
- Actins, Aged, Aromatic-L-Amino-Acid Decarboxylases, Humans, Middle Aged, Parkinson Disease, RNA, Messenger, Schizophrenia, Substantia Nigra, Tyrosine 3-Monooxygenase
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