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d-Methionine Protects Against Cisplatin-Induced Neurotoxicity in the Hippocampus of the Adult Rat

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Abstract

The hippocampus plays an important role in memory, mood, and spatial navigation. In the dentate gyrus of the adult hippocampus, in the subgranular zone (SGZ), new cells are generated, which differentiate and mature into new neurons. Cisplatin, a highly effective antineoplastic drug with nephrotoxic and ototoxic side effects, induces apoptosis and suppresses neurogenesis in the hippocampus leading to memory impairment. Previous studies have shown that the antioxidant d-methionine protects against cisplatin-induced ototoxicity and nephrotoxicity suggesting that it might also prevent neurogenesis from being suppressed by cisplatin treatment. To test this hypothesis, rats were treated with cisplatin, d-methionine, cisplatin plus d-methionine, or saline (controls). Seven days after treatment, the rats were sacrificed, and hippocampal sections immunolabeled for doublecortin (DCX) to identify neuronal precursor cells and maturing neurons in the SGZ. Cisplatin significantly reduced the number of DCX-labeled cells (~80 %) relative to controls. In contrast, DCX cell counts in rats treated with d-methionine prior to cisplatin were similar to controls. The treatment with d-methionine alone did not affect the number of DCX cells. These results indicate that d-methionine prevents the dramatic cisplatin-induced decrease of neurogenesis.

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Acknowledgments

This project was partially supported by the National Institute of Health (NIH grants R01DC00909101; R01DC009219; R01DC011808).

Ethical Standards

All animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Center for Hearing and Deafness, State University of New York at Buffalo, 137 Cary Hall, 3435 Main St, Buffalo, NY, 14214, USA

    Sneha Hinduja, Kari Suzanne Kraus, Senthilvelan Manohar & Richard J. Salvi

  2. Healthy Hearing and Balance, 1001 Washington Road, Westminster, MD, 21157, USA

    Sneha Hinduja

  3. Baumgartenstrasse 1, 77761, Schiltach, Germany

    Kari Suzanne Kraus

Authors
  1. Sneha Hinduja
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  2. Kari Suzanne Kraus
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  3. Senthilvelan Manohar
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  4. Richard J. Salvi
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Correspondence to Kari Suzanne Kraus.

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Hinduja, S., Kraus, K.S., Manohar, S. et al. d-Methionine Protects Against Cisplatin-Induced Neurotoxicity in the Hippocampus of the Adult Rat. Neurotox Res 27, 199–204 (2015). https://doi.org/10.1007/s12640-014-9503-y

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  • DOI: https://doi.org/10.1007/s12640-014-9503-y

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