UM
Identification of genes regulated by memantine and MK-801 in adult rat brain by cDNA microarray analysis
Marvanova M.; Lakso M.; Wong G.
2004-06-01
Source PublicationNeuropsychopharmacology
ISSN0893133X
Volume29Issue:6Pages:1070-1079
AbstractIn this study, we monitored gene expression profiles using cDNA microarrays after an acute systemic administration of the high affinity N-methyl-D-aspartate (NMDA) uncompetitive antagonist MK-801 (1 mg/kg; 4 h), and the clinically used moderate affinity antagonist memantine (25 mg/kg; 4 h) in adult rat brains. From a microarray containing 1090 known genes, 13 genes were regulated by both treatments of which 12 were upregulated and one was downregulated. In addition, 28 and 34 genes were regulated (≥ 1.5- or ≤ 0.67-fold change) by either memantine or MK-801, respectively. Genes commonly regulated by both treatments and not previously reported were confirmed by in situ hybridization (ISH) and include regenerating liver inhibitory factor-1 (RL/IF-1), GDP-dissociation inhibitor 1 (GDI-1), neural visinin Ca -binding protein 2 (NVP-2), neuromedin B receptor, and Na /K transporting ATPase 2β. ISH with memantine (5-50 mg/kg) revealed regulation of these genes in other cortical and hippocampal regions. RL/IF-1 induction occurred at 1 h and returned to basal levels by 8 h, consistent with the profile of an immediate early gene. Western blot analysis showed increases (∼ 30-65%) in GDI-1 protein present in both cytosolic and membrane fractions that were significant in the 84-kDa Rab bound form, suggesting that memantine influences Ras-like GTPase function. Genes regulated by a 5 mg/kg dose of memantine might be important in its therapeutic effects. These findings increase the number of known, differentially altered genes after treatment of uncompetitive NMDA receptor antagonists and suggest broader actions of these agents than previously realized.
KeywordGene expression Glutamate NMDA receptors in situ hybridization Memantine Microarray MK-801
DOI10.1038/sj.npp.1300398
URLView the original
Language英語
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Cited Times [WOS]:29   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
AffiliationItä-Suomen yliopisto
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GB/T 7714
Marvanova M.,Lakso M.,Wong G.. Identification of genes regulated by memantine and MK-801 in adult rat brain by cDNA microarray analysis[J]. Neuropsychopharmacology,2004,29(6):1070-1079.
APA Marvanova M.,Lakso M.,&Wong G..(2004).Identification of genes regulated by memantine and MK-801 in adult rat brain by cDNA microarray analysis.Neuropsychopharmacology,29(6),1070-1079.
MLA Marvanova M.,et al."Identification of genes regulated by memantine and MK-801 in adult rat brain by cDNA microarray analysis".Neuropsychopharmacology 29.6(2004):1070-1079.
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