Glutamate regulation of GDNF gene expression in the striatum and primary striatal astrocytes.
The aim of this study was to investigate the regulation of glial cell line-derived neurotrophic factor (GDNF) mRNA by activation of glutamate receptors in the rat striatum. We observed an increase in GDNF mRNA levels in the adult rat striatum after administration of subseizure doses of N-methyl-D,L-aspartic acid (NMA) and kainic acid. Since it is unclear whether the upregulation of GDNF occurred in neurons or astrocytes within the striatum, we further investigated whether GDNF gene expression in primary striatal astrocytes in culture could be regulated by glutamate receptor activation. We found that treatment of the cultures with NMA and kainic acid similarly upregulated GDNF gene expression as observed in vivo, suggesting that striatal astrocytes express functional glutamate receptors. Immunocytochemical and nuclease protection analysis revealed that striatal astrocytes expressed the NMDA-R1 subunit. These findings suggest the regulation of GDNF mRNA in the striatum may be mediated by excitation of glutamate receptors via glutamatergic cortical afferents.
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018698:Glutamic Acid / Q000502:physiology*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D007608:Kainic Acid