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Activity-dependent regulation of genes implicated in X-linked non-specific mental retardation
|Published in||Neuroscience. 2002, vol. 114, no. 1, p. 13-17|
|Abstract||X-linked forms of non-specific mental retardation are complex disorders, for which mutations in several genes have recently been identified. These include OPHN1, GDI1, PAK3, IL1RAPL, TM4SF2, FMR2 and RSK2. To investigate the mechanisms through which alterations of these gene products could result in cognitive impairment, we analyzed their expression using quantitative PCR technique in two in vitro models of activity-dependent gene regulation: kainate-induced seizures and long-term synaptic potentiation (LTP). We found that the level of expression of four genes, PAK3, IL1RAPL, RSK2 and TM4SF2, was significantly up-regulated following kainate treatment. Furthermore we observed a significant increase in mRNA levels of PAK3 and IL1RAPL following LTP induction. These results suggest a possible role for these four genes in activity-dependent brain plasticity.|
|Keywords||Action Potentials/genetics — Animals — Brain-Derived Neurotrophic Factor/genetics — Connexins/genetics — Excitatory Amino Acid Agonists/diagnostic use/pharmacology — Eye Proteins/genetics — Gene Expression Regulation/ physiology — Hippocampus/drug effects/metabolism/physiopathology — Interleukin-1 Receptor Accessory Protein — Kainic Acid/diagnostic use/pharmacology — Linkage (Genetics)/ genetics — Long-Term Potentiation/ genetics — Mental Retardation/ genetics/metabolism/physiopathology — Mice — Organ Culture Techniques — Potassium Channels/genetics — Potassium Channels, Calcium-Activated — Protein-Serine-Threonine Kinases/genetics — RNA, Messenger/metabolism — Receptors, Interleukin-1/genetics — Seizures/chemically induced/ genetics/physiopathology — Small-Conductance Calcium-Activated Potassium Channels — Up-Regulation/ genetics — X Chromosome/ genetics — P21-Activated Kinases|