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Chronic Nicotine Treatment Increases nAChRs and Microglial Expression in Monkey Substantia Nigra After Nigrostriatal Damage

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Abstract

Our previous work had shown that long-term nicotine administration improved dopaminergic markers and nicotinic receptors (nAChRs) in the striatum of monkeys with nigrostriatal damage. The present experiments were done to determine whether nicotine treatment also led to changes in the substantia nigra, the region containing dopaminergic cell bodies. Monkeys were chronically treated with nicotine in the drinking water for 6 months after which they were injected with low dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydrophridine (MPTP) for a further 6-month period. Nicotine was administered until the monkeys were euthanized 2 months after the last MPTP injection. Nicotine treatment did not affect the dopamine transporter or the number of tyrosine hydroxylase positive cells in the substantia nigra of lesioned monkeys. However, nicotine administration did lead to a greater increase in α3/α6β2* and α4β2* nAChRs in lesioned monkeys compared to controls. Nicotine also significantly elevated microglia and reduced the number of extracellular neuromelanin deposits in the substantia nigra of MPTP-lesioned monkeys. These findings indicate that long-term nicotine treatment modulates expression of several molecular measures in monkey substantia nigra that may result in an improvement in nigral integrity and/or function. These observations may have therapeutic implications for Parkinson’s disease.

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Acknowledgements

The authors thank Dr. Hong Fan, Department of Radiology, Johns Hopkins University School of Medicine, for the 125I-A85380 and 125I-epibatidine used in this study. This work is supported by NIH grants NS42091 and U54 ES012077 to MQ, and MH53631, GM 48677 and DA12242 to JMM.

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Authors and Affiliations

  1. The Parkinson’s Institute, 675 Almanor Ave, Sunnyvale, CA, 94085, USA

    Maryka Quik, Carla Campos, Neeraja Parameswaran, J. William Langston & Michael Yeluashvili

  2. Department of Biology and Psychiatry, University of Utah, Salt Lake, UT, USA

    J. Michael McIntosh

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  1. Maryka Quik
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  2. Carla Campos
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  3. Neeraja Parameswaran
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  4. J. William Langston
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Correspondence to Maryka Quik.

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Proceedings of the XIII International Symposium on Cholinergic Mechanisms

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Quik, M., Campos, C., Parameswaran, N. et al. Chronic Nicotine Treatment Increases nAChRs and Microglial Expression in Monkey Substantia Nigra After Nigrostriatal Damage. J Mol Neurosci 40, 105–113 (2010). https://doi.org/10.1007/s12031-009-9265-9

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