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The nigrostriatal DA pathway and Parkinson’s disease

  • Conference paper
Parkinson’s Disease and Related Disorders

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 70))

Summary

The discovery of the nigrostriatal DA system in the rat was made possible by the highly specific and sensitive histochemical fluorescence method of Falck and Hillarp in combinations with electrolytic lesions in the substantia nigra and removal of major parts of the neostriatum. Recent work on DA neuron evolution shows that in the Bottlenose Dolphin the normal DA cell groups of the substantia nigra are very cell sparse, while there is a substantial expansion of the A9 medial and A10 lateral subdivisions forming an impressive “ventral wing” in the posterior substantia nigra. The nigrostriatal DA pathway mainly operates via Volume Transmission. Thus, DA diffuses along concentration gradients in the ECF to reach target cells with high affinity DA receptors. A novel feature of the DA receptor subtypes is their physical interaction in the plasma membrane of striatal neurons forming receptor mosaics (RM) with the existence of two types of RM. The “functional decoding unit” for DA is not the single receptor, but rather the RM that may affect not only the integration of signals in the DA neurons but also their trophic conditions. In 1991 A2A receptor antagonists were indicated to represent novel antiparkinsonian drugs based on the existence of A2A/D2 receptor-receptor interactions and here P2X receptor antagonists are postulated to be neuroprotective drugs in treatment of Parkinson’s Disease.

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Authors and Affiliations

  1. Department of Neuroscience, Karolinska Institutet, 171 77, Stockholm, Sweden

    Prof. K. Fuxe

  2. School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg, Republic of South Africa

    P. Manger

  3. Section of Physiology, Department of Biomedical Sciences, University of Modena, Modena, Italy

    S. Genedani & L. Agnati

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  2. P. Manger
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  3. S. Genedani
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  4. L. Agnati
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Editors and Affiliations

  1. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Würzburg, Germany

    P. Riederer  & M. Gerlach  & 

  2. Universitätsklinikum der TU Dresden, Dresden, Germany

    H. Reichmann

  3. Israel Institute of Technology, Haifa, Israel

    M. B. H. Youdim

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Fuxe, K., Manger, P., Genedani, S., Agnati, L. (2006). The nigrostriatal DA pathway and Parkinson’s disease. In: Riederer, P., Reichmann, H., Youdim, M.B.H., Gerlach, M. (eds) Parkinson’s Disease and Related Disorders. Journal of Neural Transmission. Supplementa, vol 70. Springer, Vienna . https://doi.org/10.1007/978-3-211-45295-0_13

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