Brain-Derived Neurotrophic Factor Is Required for the Neuroprotective Effect of Mifepristone on Immature Purkinje Cells in Cerebellar Slice Culture

Int J Mol Sci. 2019 Jan 12;20(2):285. doi: 10.3390/ijms20020285.

Abstract

Endogenous γ-aminobutyric acid (GABA)-dependent activity induces death of developing Purkinje neurons in mouse organotypic cerebellar cultures and the synthetic steroid mifepristone blocks this effect. Here, using brain-derived neurotrophic factor (BDNF) heterozygous mice, we show that BDNF plays no role in immature Purkinje cell death. However, interestingly, BDNF haploinsufficiency impairs neuronal survival induced by mifepristone and GABAA-receptors antagonist (bicuculline) treatments, indicating that the underlying neuroprotective mechanism requires the neurotrophin full expression.

Keywords: BDNF; GABAA receptors; MAP-kinase; Purkinje cells; mifepristone.

MeSH terms

  • Animals
  • Apoptosis
  • Bicuculline / pharmacology
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Survival
  • Cells, Cultured
  • Haploinsufficiency
  • Mice
  • Mifepristone / pharmacology*
  • Neuroprotective Agents / pharmacology*
  • Purkinje Cells / cytology*
  • Purkinje Cells / drug effects
  • Purkinje Cells / metabolism
  • gamma-Aminobutyric Acid / adverse effects*

Substances

  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • Mifepristone
  • gamma-Aminobutyric Acid
  • Bicuculline