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Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants pp 145–164Cite as

Restoration of Damaged Dopamine Neurons

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Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 1))

Abstract

Several in vitro and in vivo studies demonstrate that some β-carbolines (βC) exert neuroprotective effects. The noncationic 9-methyl-βC enhanced the enzyme activity of triosephosphate isomerase (TPI), whereas the cationic 2-methyl-βC and 2,9-dimethyl-βC inhibited enzyme activity. TPI is a rate-limiting enzyme for glycolysis and its activation improves the energy supply of the cell. In murine primary neurons, exposition to 9-methyl-βC increased the number of dopamine (DA) neurons by up to 50% and of gene transcripts of several genes involved in differentiation while transcripts of proinflammation, proapoptosis, and stress were downregulated. Chronic exposure to rotenone, a toxin which acts by inhibiting complex I of the respiratory chain, decreased the number of DA neurons. After rotenone withdrawal further deterioration was observed as well as ongoing proliferation of microglia. Exposure of cultures to 9-methyl-βC after rotenone withdrawal, resulted in conspicuous regeneration of DA neurons and a reversal of the number of microglia. In an animal model of PD, 9-methyl-βC normalized the decline of DA levels in the striatum. Expression of genes involved in neuronal differentiation, regeneration, and survival were upregulated including brain-derived neurotrophic factor, conserved DA neurotrophic factor, and nerve growth factor while transcripts of inflammation and apoptosis-inducing factors were downregulated. Further neuroprotective effects are reported in Chaps. 8 and 9.

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Authors and Affiliations

  1. Department of Psychiatry, Charité-University Medicine, Campus Benjamin Franklin, Charitéplatz 1, 10117, Berlin, Germany

    Hans Rommelspacher

  2. Department of Psychiatry, Charité-University Medicine, Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany

    Hans Rommelspacher & Catrin Wernicke

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  1. Hans Rommelspacher
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  2. Catrin Wernicke
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Correspondence to Hans Rommelspacher .

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  1. Smetna 12, Krakow, 31-343, Poland

    Lucyna Antkiewicz-Michaluk

  2. , Departments of Psychiatry, Charité-University Medicine, Berlin, 10117, Germany

    Hans Rommelspacher

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Rommelspacher, H., Wernicke, C. (2012). Restoration of Damaged Dopamine Neurons. In: Antkiewicz-Michaluk, L., Rommelspacher, H. (eds) Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants. Current Topics in Neurotoxicity, vol 1. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1542-8_10

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