High levels of a retinoic acid-generating dehydrogenase in the meso-telencephalic dopamine system.
Open accessAbstract
Retinoic acid is synthesized from retinaldehyde by several different dehydrogenases, which are arranged in conserved spatial and developmentally regulated patterns. Here we show for the mouse that a class-1 aldehyde dehydrogenase, characterized by oxidation and disulfiram sensitivity, is found in the brain at high levels only in the basal forebrain. It is present in axons and terminals of a subpopulation of dopaminergic neurons of the mesostriatal and mesolimbic system, forming a retinoic acid-generating projection from the ventral tegmentum to the corpus striatum and the shell of the nucleus accumbens. In the striatum the projection is heaviest to dorsal and rostral regions, declining gradually toward ventral. The enzyme is expressed early in development, shortly after appearance of tyrosine hydroxylase. Other dopaminergic neurons in the brain, as well as the chromaffin cells of the adrenal medulla, do not contain this dehydrogenase. The presence of this enzyme may be a factor in the long-term success of transplants of dopaminergic cells to the corpus striatum in Parkinson disease, and it may play a role in parkinsonism and catatonia due to disulfiram (Antabuse) neurotoxicity.
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In experimental models of PD, RA protected against neurodegeneration of midbrain dopaminergic neurons in the substantia nigra.
“In experimental models of PD, RA protected against neurodegeneration of midbrain dopaminergic neurons in the substantia nigra86,87.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [86]
Cites
PERIODATE-LYSINE-PARAFORMALDEHYDE FIXATIVE A NEW FIXATIVE FOR IMMUNOELECTRON MICROSCOPY
McLean, I. W., & Nakane, P. K. (1974) · Journal of Histochemistry & Cytochemistry · doi:10.1177/22.12.1077 · Cited by 3,817 · see citing works
Characterization of three RXR genes that mediate the action of 9-cis retinoic acid.Preprint
Mangelsdorf, D. J., Borgmeyer, U., Heyman, R. A., Zhou, J. Y., Ong, E. S., Oro, A. E., Kakizuka, A., & Evans, R. M. (1992) · Genes & Development · doi:10.1101/gad.6.3.329 · Cited by 1,193 · see citing works
Specht, L. A., Pickel, V. M., JOH, T. H., & Reis, D. J. (1981) · The Journal of Comparative Neurology · doi:10.1002/cne.901990208 · Cited by 497 · see citing works
Aldehyde Dehydrogenases and Their Role in Carcinogenesis
Lindahl, R. G. (1992) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409239209082565 · Cited by 402 · see citing works
Kaplan, D. R., Matsumoto, K., Lucarelli, E., & Thielet, C. J. (1993) · Neuron · doi:10.1016/0896-6273(93)90187-v · Cited by 345 · see citing works
Greenfield, N. J., & Pietruszko, R. (1977) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(77)90005-5 · Cited by 314 · see citing works
Wagner, M., Han, B., & Jessell, T. M. (1992) · Development · doi:10.1242/dev.116.1.55 · Cited by 246 · see citing works
Asymmetrical retinoic acid synthesis in the dorsoventral axis of the retina
McCaffery, P. J. A., Lee, M., Wagner, M. A., Sládek, N. E., & Dräger, U. C. (1992) · Development · doi:10.1242/dev.115.2.371 · Cited by 241 · see citing works
Self-citationHuman Aldehyde Dehydrogenase: Mechanism of Inhibition of Disulfiram
Vallari, R. C., & Pietruszko, R. (1982) · Science · doi:10.1126/science.7071604 · Cited by 235 · see citing works
Ruberte, E., Friederich, V., Chambon, P., & Morriss‐Kay, G. M. (1993) · Development · doi:10.1242/dev.118.1.267 · Cited by 221 · see citing works
Horse Liver Aldehyde Dehydrogenase
Feldman, R. I., & Weiner, H. (1972) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)45784-0 · Cited by 209 · see citing works
Duester, G., Shean, M. L., McBride, M. S., & Stewart, M. J. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.3.1638 · Cited by 186 · see citing works
Aldehyde dehydrogenase from human liver
Hempel, J. D., von Bahr‐Lindström, H., & Jörnvall, H. (1984) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1984.tb08150.x · Cited by 171 · see citing works
Changing Patterns of the Retinoic Acid System in the Developing Retina
McCaffery, P. J. A., Posch, K. C., Napoli, J. L., et al. (1993) · Developmental Biology · doi:10.1006/dbio.1993.1197 · Cited by 164 · see citing works
Self-citationAldehyde dehydrogenase is a positional marker in the retina
McCaffery, P. J. A., Tempst, P., Lara, G., & Dräger, U. C. (1991) · Development · doi:10.1242/dev.112.3.693 · Cited by 153 · see citing works
Self-citationLee, M., Manthey, C. L., & Sládek, N. E. (1991) · Biochemical Pharmacology · doi:10.1016/0006-2952(91)90266-8 · Cited by 150 · see citing works
Hot spots of retinoic acid synthesis in the developing spinal cord.
McCaffery, P. J. A., & Dräger, U. C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.15.7194 · Cited by 147 · see citing works
Self-citationRoffler-Tarlov, S. K., & Graybiel, A. M. (1984) · Nature · doi:10.1038/307062a0 · Cited by 136 · see citing works
Characterization of cytosolic aldehyde dehydrogenase from cyclophosphamide resistant L1210 cells.
Russo, J. E., & Hilton, A. (1988) · PubMed · Cited by 118 · see citing works
Rat liver aldehyde dehydrogenase. II. Isolation and characterization of four inducible isozymes.
Lindahl, R. G., & Evces, S. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)71308-6 · Cited by 96 · see citing works
'Catatonia' due to Disulfiram Toxicity
Fisher, C. (1989) · Archives of Neurology · doi:10.1001/archneur.1989.00520430094024 · Cited by 94 · see citing works
Histochemical Study of Aldehyde Dehydrogenase in the Rat CNS
Zimatkin, S. M. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb02555.x · Cited by 84 · see citing works
Lesions of basal ganglia due to disulfiram neurotoxicity.
Laplane, D., Attal, N., Sauron, B., de Billy, A., & Dubois, B. (1992) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.55.10.925 · Cited by 74 · see citing works
Identification of the mouse aldehyde dehydrogenases important in aldophosphamide detoxification.
Manthey, C. L., Landkamer, G. J., & Sládek, N. E. (1990) · PubMed · Cited by 69 · see citing works
Dystonia and akinesia due to pallidoputaminal lesions after disulfiram intoxication
Krauss, J. K., Mohadjer, M., Wakhloo, A. K., et al. (1991) · Movement Disorders · doi:10.1002/mds.870060214 · Cited by 60 · see citing works
Vitamin A mediated gene expression.
Chytil, F., & Riaz-ul-Haq (1990) · PubMed · Cited by 56 · see citing works
Duester, G., Shean, M. L., McBride, M. S., et al. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.3.1638-1646.1991 · Cited by 22 · see citing works
Tank, A. W., Deitrich, R. A., & Weiner, H. (1986) · Biochemical Pharmacology · doi:10.1016/0006-2952(86)90779-3 · Cited by 13 · see citing works
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Maden, M. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2212 · Cited by 896 · see citing works
Retinoid signalling in the development of the central nervous system
Maden, M. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn963 · Cited by 428 · see citing works
Chung, C. Y., Seo, H., Sonntag, K. C., Brooks, A., Lin, L., & Isacson, O. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi178 · Cited by 361 · see citing works
Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling
Poulin, J.-F., Zou, J., Drouin-Ouellet, J., Kim, K.-Y. A., Cicchetti, F., & Awatramani, R. B. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.008 · Cited by 352 · see citing works
The foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old age
Kittappa, R., Chang, W. W., Awatramani, R. B., & McKay, R. D. G. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050325 · Cited by 251 · see citing works
Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons
Kim, J.-I., Ganesan, S., Luo, S. X., Wu, Y.-W., Park, E., Huang, E. J., Chen, L., & Ding, J. B. (2015) · Science · doi:10.1126/science.aac4690 · Cited by 217 · see citing works
Aldehyde dehydrogenase 1 defines and protects a nigrostriatal dopaminergic neuron subpopulation
Liu, G., Yu, J., Ding, J., Xie, C., Sun, L., Rudenko, I., Zheng, W., Sastry, N., Luo, J., Rudow, G., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72176 · Cited by 166 · see citing works
Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine
Ferreira, R., Napoli, J., Enver, T., Bernardino, L., & Ferreira, L. (2020) · Nature Communications · doi:10.1038/s41467-020-18042-2 · Cited by 138 · see citing works
Wu, J., Kung, J., Dong, J., Chang, L., Xie, C., Habib, A., Hawes, S., Yang, N., Chen, V., Liu, Z., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.095 · Cited by 87 · see citing works
Esteves, M., Cristóvão, A. C., Saraiva, T., Rocha, S. M., Baltazar, G., Ferreira, L., & Bernardino, L. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00020 · Cited by 88 · see citing works
Di Salvio, M., Di Giovannantonio, L. G., Omodei, D., Acampora, D., & Simeone, A. (2010) · The International Journal of Developmental Biology · doi:10.1387/ijdb.092974ms · Cited by 86 · see citing works
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Melani, R., & Tritsch, N. X. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110716 · Cited by 56 · see citing works
Sgobio, C., Wu, J., Zheng, W., Chen, X., Pan, J., Salinas, A. G., Davis, M. I., Lovinger, D. M., & Cai, H. (2017) · Scientific Reports · doi:10.1038/s41598-017-05598-1 · Cited by 47 · see citing works
- Authors
- McCaffery, P., & Dräger, U. C.
- Affiliations
- Division of Developmental Neuroscience, E. K. Shriver Center, Waltham, MA 02254.
- Harvard University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-08-02
- Volume
- 91
- Issue
- 16
- Pages
- 7772-7776
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC44484
- OpenAlex
- W2071230039
- Cited by
- 266
- References
- 28
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2022: 5 · 2021: 8 · 2020: 9 · 2019: 3 · 2018: 1 · 2017: 8 · 2016: 8 · 2015: 11 · 2014: 11 · 2013: 10 · 2012: 7
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (R01EY001938)
- 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
- retinoic acid synthesis, aldehyde dehydrogenase, dopaminergic neurons, mesolimbic dopamine system, ventral tegmental area, striatum, nucleus accumbens shell, basal forebrain, tyrosine hydroxylase, dopaminergic cell transplantation, Parkinson's disease, catatonia, parkinsonism, brain development
- MeSH terms
- Alcohol Dehydrogenase, Aldehyde Dehydrogenase, Animals, Basal Ganglia, Corpus Striatum, Disulfiram, Dopamine, Hippocampus, Immunohistochemistry, Nucleus Accumbens, Olfactory Bulb, Telencephalon, Tissue Distribution, Tretinoin, Mice
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