Glial proliferation and metabotropic glutamate receptor expression in amyotrophic lateral sclerosis.
Accumulating evidence indicates that alterations in glial activation and disturbances in glial glutamate metabolism may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). Metabotropic glutamate receptors (mGluRs) are involved in glutamate homeostasis as well as in glial proliferation. Using in situ hybridization and immunohistochemistry we found a strong upregulation of group I and group II mGluR mRNA and protein in ALS spinal cord as compared to controls (mGluR5 > mGluR1 > mGluR2/3). In vitro, the mGluR group I agonist 3,5-dihydroxyphenylglycine induced proliferation in chick spinal cord astroglial cultures. Moreover, addition of cerebrospinal fluid (CSF) from ALS patients resulted in significantly higher proliferation rates than control CSF. In both cases, the effect could be blocked by addition of the mGluR group I antagonist 1-aminoindan-1,5-dicarboxylic acid. Taken together, our data suggest that stimulation of glial mGluRs through mediators present in the CSF may contribute to glial proliferation and astrogliosis in ALS.
Anneser
Johanna M H
JM
Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, Munich, Germany. Johanna.Anneser@nro.med.uni-muenchen.de
Chahli
Christine
C
Ince
Paul G
PG
Borasio
Gian Domenico
GD
Shaw
Pamela J
PJ
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000096:biosynthesis*
D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate