Antibodies directed to Neisseria gonorrhoeae impair nerve growth factor-dependent neurite outgrowth in Rat PC12 cells

J Mol Neurosci. 2014 Mar;52(3):353-65. doi: 10.1007/s12031-013-0156-8. Epub 2013 Nov 8.

Abstract

In children born from mothers with prenatal infections with the Gram-negative bacterium Neisseria gonorrhoeae, schizophrenia risk is increased in later life. Since cortical neuropil formation is frequently impaired during this disease, actions of a rabbit polyclonal antiserum directed to N. gonorrhoeae on neurite outgrowth in nerve growth factor-stimulated PC12 cells were investigated here. It turned out that 10 μg/ml of the antiserum leads indeed to a significant reduction in neurite outgrowth, whereas an antiserum directed to Neisseria meningitidis had no such effect. Furthermore, reduction in neurite outgrowth could be reversed by the neuroleptic drugs haloperidol, clozapine, risperidone, and olanzapine. On the molecular level, the observed effects seem to include the known neuritogenic transcription factors FoxO3a and Stat3, since reduced neurite outgrowth caused by the antiserum was accompanied by a reduced phosphorylation of both factors. In contrast, restitution of neurite outgrowth by neuroleptic drugs revealed no correlation to the phosphorylation state of these factors. The present report gives a first hint that bacterial infections could indeed lead to impaired neuropil formation in vitro; however, the in vivo relevance of this finding for schizophrenia pathogenesis remains to be clarified in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / pharmacology*
  • Antipsychotic Agents / pharmacology
  • Cell Growth Processes
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / metabolism
  • Neisseria gonorrhoeae / immunology*
  • Neisseria meningitidis / immunology
  • Neurites / drug effects*
  • Neurites / metabolism
  • Neurites / physiology
  • PC12 Cells
  • Phosphorylation
  • Rats
  • STAT3 Transcription Factor / metabolism
  • Species Specificity

Substances

  • Antibodies, Bacterial
  • Antipsychotic Agents
  • FOXO3 protein, rat
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • STAT3 Transcription Factor