K-252a promotes survival and choline acetyltransferase activity in striatal and basal forebrain neuronal cultures

J Neurochem. 1995 Apr;64(4):1502-12. doi: 10.1046/j.1471-4159.1995.64041502.x.


The organic molecule K-252a promoted cell survival, neurite outgrowth, and increased choline acetyltransferase (ChAT) activity in rat embryonic striatal and basal forebrain cultures in a concentration-dependent manner. A two- to threefold increase in survival was observed at 75 nM K-252a in both systems. A single application of K-252a at culture initiation prevented substantial (> 60%) cell death that otherwise occurred after 4 days in striatal or basal forebrain cultures. A 5-h exposure of striatal or basal forebrain cells to K-252a, followed by its removal, resulted in survival equivalent to that observed in cultures continually maintained in its presence. This is in contrast to results found with a 5-h exposure of basal forebrain cultures to nerve growth factor (NGF). Acute exposure of basal forebrain cultures to K-252a, but not to NGF, increased ChAT activity, indicating that NGF was required the entire culture period for maximum activity. Striatal cholinergic and GABAergic neurons were among the neurons rescued by K-252a. Of the protein growth factors tested in striatal cultures (ciliary neurotrophic factor, neurotrophin-3, NGF, brain-derived neurotrophic factor, interleukin-2, basic fibroblast growth factor), only brain-derived neurotrophic factor promoted survival. The enhancement of survival and ChAT activity of basal forebrain and striatal neurons by K-252a defines additional populations of neurons in which survival and/or differentiation is regulated by a K-252a-responsive mechanism. The above results expand the potential therapeutic targets for these molecules for the treatment of neuro-degenerative diseases.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Carbazoles / metabolism
  • Carbazoles / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Choline O-Acetyltransferase / metabolism*
  • Corpus Striatum / cytology
  • Corpus Striatum / enzymology*
  • Indole Alkaloids
  • Nerve Growth Factors / pharmacology
  • Neurons / drug effects
  • Neurons / enzymology*
  • Neurons / physiology*
  • Parasympathetic Nervous System / cytology
  • Prosencephalon / cytology
  • Prosencephalon / enzymology*
  • Protein Kinase C / antagonists & inhibitors
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • gamma-Aminobutyric Acid / physiology


  • Carbazoles
  • Indole Alkaloids
  • Nerve Growth Factors
  • gamma-Aminobutyric Acid
  • staurosporine aglycone
  • Choline O-Acetyltransferase
  • Protein Kinase C