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Expression of transgenes in midbrain dopamine neurons using the tyrosine hydroxylase promoter

Gene Therapy volume 16, pages 437–440 (2009)Cite this article

Abstract

Billions of neurons are interconnected in the central nervous system (CNS). Identification of specific neuronal circuit is indispensable for understanding the relationship between structure and function in the CNS. The midbrain dopamine (DA) neuron system consists of the retrorubral area (A8), the substantia nigra (SN; A9) and the ventral tegmental area (VTA; A10). We hypothesized that genetic methods using cell-type-specific promoters may offer the possibility to express tracer molecules in DA neurons to facilitate neuronal tracing. To address this, we used the 2.5 kb rat tyrosine hydroxylase (TH) promoter in adenovirus or adeno-associated virus (AAV) to express tracers specifically in DA neurons. We found that stereotaxic injection of TH promoter containing adenoviral construct resulted in cell-type-specific transgene expression in the noradrenaline (NA) neurons of the locus coeruleus (LC). However, it caused a significant toxicity to DA neurons in the SN. In contrast, stereotaxic injection of TH promoter containing AAV to the SN resulted in cell-type-specific transgene expression in DA neurons with no detectable toxicity. Taken together, our results demonstrate that it is possible to selectively trace DA neuronal circuits in rodent brains using the TH promoter in the context of AAV.

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Acknowledgements

This work was supported by NIH Grants DC006501 and MH48866, and an International Grant from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea, and the Korea Research Foundation Grant KRF-2006–214-E00037.

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Author notes

  1. S J Hong

    Present address: 4Present address: Department of Surgery, Laboratory for Wound Healing and Regenerative Medicine, Northwestern University Medical School, 300 E Superior Street, Chicago, IL 60611, USA.,

  2. M S Oh and S J Hong: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, Molecular Neurobiology Laboratory, McLean Hospital and Harvard Medical School, Belmont, MA, USA

    M S Oh, S J Hong & K-S Kim

  2. Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, Korea

    M S Oh

  3. Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, Korea

    Y Huh

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  1. M S Oh
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Corresponding author

Correspondence to K-S Kim.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Oh, M., Hong, S., Huh, Y. et al. Expression of transgenes in midbrain dopamine neurons using the tyrosine hydroxylase promoter. Gene Ther 16, 437–440 (2009). https://doi.org/10.1038/gt.2008.148

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