Elsevier

Brain Research

Volume 816, Issue 1, 16 January 1999, Pages 225-228
Brain Research

Short communication
α7 Nicotinic receptor mediated protection against ethanol-induced cytotoxicity in PC12 cells

https://doi.org/10.1016/S0006-8993(98)01153-6Get rights and content

Abstract

Ethanol caused a concentration-dependent loss of PC12 cells over a 24 h interval, accompanied by an increase in intracellular calcium. The specific α7 nicotinic receptor partial agonist DMXB attenuated both of these ethanol-induced actions at a concentration (3 μM) found previously to protect against apoptotic and necrotic cell loss. The α7 nicotinic receptor antagonist methylylaconitine blocked the neuroprotective action of DMXB when applied with but not 30 min after the agonist. These results indicate that activation of α7 nicotinic receptors may be therapeutically useful in preventing ethanol-neurotoxicity.

Section snippets

Acknowledgements

We thank Melissa Chen and Neal Benson of the University of Florida ICBR for their expert technical support with the flow cytometry. This work was funded in part by NIAAA RO1 AA11597, T32 AA07561, and PO1 AG10485.

References (25)

  • H. Kitagawa et al.

    Phase I studies of GTS-21 to assess the safety, tolerability, PK and effects on measures of cognitive function in normal volunteers

    Neurobiol. Aging

    (1998)
  • P. Leisi

    Ethanol-exposed central neurons fail to migrate and undergo apoptosis

    J. Neurosci. Res.

    (1997)
  • Cited by (34)

    • In biomarkers of developmental neurotoxicity

      2022, Reproductive and Developmental Toxicology
    • In vitro biomarkers of developmental neurotoxicity

      2017, Reproductive and Developmental Toxicology
    • Alpha7 nicotinic receptors as therapeutic targets for Parkinson's disease

      2015, Biochemical Pharmacology
      Citation Excerpt :

      The idea that α7 nAChRs had a role in neuroprotection initially arose from results showing that α7 nAChR antagonists prevented nicotine, choline or acetylcholinesterase inhibitor-mediated protection against toxic insults in neuronal cell cultures (Table 1). α7 nAChR antagonists such as methyllycaconitine (MLA) or α-bungarotoxin (α-BTX) attenuated nAChR-mediated protection against amyloid-β, glutamate and NMDA toxicity, as well as growth factor and oxygen–glucose deprivation in cell lines and primary neuronal cultures [46–58]. Conversely, α7 nAChR agonists afforded neuroprotection.

    • In vitro biomarkers of developmental neurotoxicity

      2011, Reproductive and Developmental Toxicology
    • The α7 nicotinic receptor agonist 4OH-GTS-21 protects axotomized septohippocampal cholinergic neurons in wild type but not amyloid-overexpressing transgenic mice

      2007, Neuroscience
      Citation Excerpt :

      The loss of septohippocampal cholinergic neurons is one of the early deficits seen in AD. Because α7 nicotinic receptor agonists can prevent cytotoxicity caused by NGF-deprivation in vitro (Li et al., 1999b), we hypothesized that 4OH-GTS-21 would protect axotomized, NGF-responsive, septal cholinergic neurons as well. The present results support this hypothesis in wild type mice, demonstrating for the first time that chronic treatment with a selective α7 nicotinic receptor agonist can protect against the loss and atrophy of axotomized septal cholinergic neurons.

    • α7 Nicotinic receptor gene delivery into mouse hippocampal neurons leads to functional receptor expression, improved spatial memory-related performance, and tau hyperphosphorylation

      2007, Neuroscience
      Citation Excerpt :

      Three days later, cells were either assayed for high affinity [3H]MLA binding or treated for another 2 days with specified GTS-21 concentrations to determine its effect on cell viability. The number of cells remaining at that time was used to estimate viability, based on counting the total number of cells at three random sites/plate (Li et al., 1999a). C57BL/6 mice and α7 KO mice from the same strain were obtained from the Jackson Laboratories (Bar Harbor, ME, USA).

    View all citing articles on Scopus
    View full text