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Research ArticleExperimental Studies

Ampakines Attenuate Staurosporine-induced Cell Death in Primary Cortical Neurons: Implications in the ‘Chemo-Brain’ Phenomenon

DANIEL P. RADIN, GARY A. ROGERS, KIMBERLEY E. HEWITT, RICHARD PURCELL and ARNOLD LIPPA
Anticancer Research June 2018, 38 (6) 3461-3465; DOI: https://doi.org/10.21873/anticanres.12615
DANIEL P. RADIN
RespireRx Pharmaceuticals, Inc., Glen Rock, NJ, U.S.A.
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  • For correspondence: dradin@respirerx.com
GARY A. ROGERS
RespireRx Pharmaceuticals, Inc., Glen Rock, NJ, U.S.A.
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KIMBERLEY E. HEWITT
RespireRx Pharmaceuticals, Inc., Glen Rock, NJ, U.S.A.
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RICHARD PURCELL
RespireRx Pharmaceuticals, Inc., Glen Rock, NJ, U.S.A.
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ARNOLD LIPPA
RespireRx Pharmaceuticals, Inc., Glen Rock, NJ, U.S.A.
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Abstract

Background/Aim: Mounting evidence suggests that trophic cell signaling can be mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation. It has been demonstrated that exogenous application of brain-derived neurotrophic factor (BDNF) is highly neuroprotective in vitro against neurotoxic insults such as standard chemotherapies. Materials and Methods: Because positive allosteric modulation of AMPARs with ampakines can increase both BDNF mRNA and protein in vitro and in vivo, we examined whether application of the ampakines CX614 and CX729 promoted neuroprotection against staurosporine-induced cell death in rat primary cortical neurons using propidium iodide to stain for dead cells. Results: A transient 2-h pretreatment with CX614 or CX729 performed 24 h prior to staurosporine produced significant, time-dependent neuroprotection that was resistant to the AMPAR antagonists NBQX or GYKI 52466, suggesting that this effect may be independent of ion flow. Furthermore, the pretreatment time requirements of CX729 matched the time course for increased BDNF expression previously reported to occur in hippocampal slices, suggesting that increased neurotrophin expression might be associated with the neuroprotective effects conferred by ampakines. Conclusion: Our data demonstrate that ampakines may be able to perturb neuronal toxicity and peripheral neuropathy of front-line chemotherapies.

  • Ampakine
  • cell death
  • neuroprotection
  • neurotrophin
  • staurosporine
  • Received March 14, 2018.
  • Revision received April 23, 2018.
  • Accepted April 30, 2018.
  • Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
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Anticancer Research: 38 (6)
Anticancer Research
Vol. 38, Issue 6
June 2018
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Ampakines Attenuate Staurosporine-induced Cell Death in Primary Cortical Neurons: Implications in the ‘Chemo-Brain’ Phenomenon
DANIEL P. RADIN, GARY A. ROGERS, KIMBERLEY E. HEWITT, RICHARD PURCELL, ARNOLD LIPPA
Anticancer Research Jun 2018, 38 (6) 3461-3465; DOI: 10.21873/anticanres.12615

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Ampakines Attenuate Staurosporine-induced Cell Death in Primary Cortical Neurons: Implications in the ‘Chemo-Brain’ Phenomenon
DANIEL P. RADIN, GARY A. ROGERS, KIMBERLEY E. HEWITT, RICHARD PURCELL, ARNOLD LIPPA
Anticancer Research Jun 2018, 38 (6) 3461-3465; DOI: 10.21873/anticanres.12615
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Keywords

  • Ampakine
  • Cell death
  • neuroprotection
  • neurotrophin
  • staurosporine
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