Expression patterns of AMOG in developing human cortex and malformations of cortical development

Boer, K.; Spliet, W.G.M.; van Rijen, P.C.; Jansen, F.E.; Aronica, E.

doi:10.1016/j.eplepsyres.2010.06.015

« Previous Next »Epilepsy Research
Volume 91, Issue 1 , Pages 84-93, September 2010

Expression patterns of AMOG in developing human cortex and malformations of cortical development

K. Boer
- Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, The Netherlands
W.G.M. Spliet
- Department of Pathology, Rudolf Magnus Institute for Neurosciences, University Medical Center Utrecht, The Netherlands
P.C. van Rijen
- Department of Neurosurgery, Rudolf Magnus Institute for Neurosciences, University Medical Center Utrecht, The Netherlands
F.E. Jansen
- Department of Child Neurology, Rudolf Magnus Institute for Neurosciences, University Medical Center Utrecht, The Netherlands
E. Aronica
- Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, The Netherlands
- Epilepsy Institute of The Netherlands (SEIN), Heemstede, The Netherlands
- Corresponding author at: Department of (Neuro)Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Tel.: +31 20 5662943; fax: +31 20 5669522.

Received 30 April 2010; received in revised form 13 June 2010; accepted 29 June 2010.

Summary

Adhesion molecule on glia (AMOG) mediates neuronal migration during development and ion homeostasis. Recently, AMOG has been identified as a regulator of the Pi3K–mTOR signaling pathway. In the present study, we investigated the expression pattern of AMOG in human cortex during development and in focal malformations of cortical development.

In the developing human cortex, AMOG expression was detected in the cortical plate at 13 gestational weeks and increased in later gestational ages. In adult human control cortex, a diffuse immunoreactivity pattern was observed for AMOG in the grey matter. In the white matter, AMOG was expressed in perivascular astrocytes.

In focal cortical dysplasia (n=6) and cortical tubers (n=6), the diffuse AMOG expression pattern was reduced in the grey matter. However, AMOG immunoreactivity was observed in reactive astrocytes and strong perisomatic staining was detected in balloon and giant cells. Double-labeling showed co-localization of AMOG with the precursor cell marker CD34 and phosphorylated S6, used as a marker of mTOR activation.

The AMOG expression pattern, with altered cellular distribution, observed in malformations of cortical development suggests that AMOG might contribute to the abnormal cortical development via mTOR activation. Whether dysfunction of AMOG might influence the ionic and osmotic regulation, contributing to neuronal hyperexcitability, deserves further investigation.

Keywords: Adhesion molecule on glia, Cortical development, Focal cortical dysplasia, Tuberous sclerosis complex, Epilepsy