Regulation of choline acetyltransferase expression by 17 β-oestradiol in NSC-34 cells and in the spinal cord

J Neuroendocrinol. 2011 Sep;23(9):839-48. doi: 10.1111/j.1365-2826.2011.02192.x.

Abstract

Motoneurones located in the ventral horn of the spinal cord conciliate cholinergic innervation of skeletal muscles. These neurones appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis. The dysfunction of motoneurones is typically accompanied by alterations of cholinergic metabolism and signalling, as demonstrated by a decrease in choline acetyltransferase (ChAT) expression. 17 β-Oestradiol (E(2)) is generally accepted as neuroprotective factor in the brain under acute toxic and neurodegenerative conditions and also appears to exert a protective role for motoneurones. In the present study, we attempted to analyse the role of E(2) signalling on ChAT expression in the motoneurone-like cell line NSC-34 and in vivo. In a first step, we demonstrated the presence of oestrogen receptor α and β in NSC-34 cells, as well as in the cervical and lumbar parts, of the male mouse spinal cord. Subsequently, we investigated the effect of E(2) treatment on ChAT expression. The application of E(2) significantly increased the transcription of ChAT in NSC-34 cells and in the cervical but not lumbar part of the spinal cord. Our results indicate that E(2) can influence the cholinergic system by increasing ChAT expression in the mouse spinal cord. This mechanism might support motoneurones, in addition to survival-promoting mechanisms, in the temporal balance toxic or neurodegenerative challenges.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Choline O-Acetyltransferase / genetics
  • Choline O-Acetyltransferase / metabolism*
  • Estradiol / pharmacology*
  • Estradiol / physiology
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Neurons / drug effects*
  • Motor Neurons / enzymology*
  • Motor Neurons / physiology
  • Nuclear Receptor Coactivators / genetics
  • Nuclear Receptor Coactivators / metabolism
  • Signal Transduction
  • Spinal Cord / cytology
  • Spinal Cord / drug effects*
  • Spinal Cord / enzymology*

Substances

  • Estrogen Receptor alpha
  • NCOA7 protein, human
  • Nuclear Receptor Coactivators
  • Estradiol
  • Choline O-Acetyltransferase