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Combining the lack of chromogranins with chronic L-DOPA treatment affects motor activity in mice

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Abstract

We have tested whether the lack of chromogranins (Cgs) A and B could provoke CNS disorders when combined with an excess of dopamine. We chronically treated (over 6 months) mice lacking both chromogranins A and B (Cgs-KO) with a low oral dosage of L-DOPA/benserazide (10/2.5 mg/kg). Motor performance in the rota-rod test, open field activity, and metabolic cages indicated a progressive impairment in motor coordination in these mice, and an increase in rearing behavior, which was accompanied by an increase in DA within the substantia nigra. We conclude that mild chronic L-DOPA treatment does not produce nigro-striatal toxicity that could be associated with parkinsonism, neither in control nor Cgs-KO mice. Rather, Cgs-KO mice exhibit behaviors compatible with an amphetamine-like effect, probably caused by the excess of catecholamines in the CNS.

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Acknowledgments

We thank Ms. Lidia Ruiz for her excellent work in processing the tissue for microscopy, and our discussions with Dr. Daniel Marcellino (Department of Integrative Medical Biology, Umeå, Sweden) were greatly appreciated.

Funding

This work was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (BFU2017-82618-P). LCR received a PhD fellowship from Fundación CajaCanarias (Spain).

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Author notes

  1. Leandro Castañeyra-Ruiz

    Present address: Department of Neurosurgery, School of Medicine, Washington University in Saint Louis, St. Louis, MO, USA

Authors and Affiliations

  1. Department of Neurosurgery, School of Medicine, Washington University in Saint Louis, St. Louis, MO, USA

    Ayoze González-Santana

  2. Unidad de Farmacología, Facultad de Medicina, Universidad de La Laguna, E-38200, La Laguna, Tenerife, Spain

    Leandro Castañeyra-Ruiz, Ayoze González-Santana, José D. Machado & Ricardo Borges

  3. Dept. Ciencias Médicas Basicas, Facultad de Medicina, Universidad de La Laguna, Tenerife, Spain

    Agustín Castañeyra & Ayoze González-Santana

Authors
  1. Leandro Castañeyra-Ruiz
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  2. Agustín Castañeyra
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  3. Ayoze González-Santana
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  4. José D. Machado
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  5. Ricardo Borges
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Corresponding author

Correspondence to Ricardo Borges.

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All procedures involving animals were performed in accordance with institutional (Universidad de La Laguna, CEIBA-2014-0125a) and national guidelines, and in compliance with the EU guidelines in directive EC/63/2010.

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Castañeyra-Ruiz, L., Castañeyra, A., González-Santana, A. et al. Combining the lack of chromogranins with chronic L-DOPA treatment affects motor activity in mice. Cell Tissue Res 380, 59–66 (2020). https://doi.org/10.1007/s00441-019-03159-8

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  • DOI: https://doi.org/10.1007/s00441-019-03159-8

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