Activity-dependent regulation of genes implicated in X-linked non-specific mental retardation.
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.
Neuropharmacology and Department of Morphology, Centre Medical Universitaire, 1 rue Michel Servet, 1211, Geneva 4, Switzerland. bernadett.boda@medicine.unige.ch
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D000200:Action Potentials / Q000235:genetics; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D017630:Connexins / Q000235:genetics; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005136:Eye Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D008040:Genetic Linkage / Q000235:genetics*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D053577:Interleukin-1 Receptor Accessory Protein; D007608:Kainic Acid / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000235:genetics*; D051379:Mice; D009924:Organ Culture Techniques; D015221:Potassium Channels / Q000235:genetics; D024681:Potassium Channels, Calcium-Activated; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics; D012640:Seizures / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D051640:Small-Conductance Calcium-Activated Potassium Channels; D015854:Up-Regulation / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*; D054462:p21-Activated Kinases; D000097004:Gap Junction delta-2 Protein
D019208:Brain-Derived Neurotrophic Factor; D017630:Connexins; D018690:Excitatory Amino Acid Agonists; D005136:Eye Proteins; D053577:Interleukin-1 Receptor Accessory Protein; D007608:Kainic Acid; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D051640:Small-Conductance Calcium-Activated Potassium Channels; D054462:p21-Activated Kinases; D000097004:Gap Junction delta-2 Protein; C407643:IL1RAPL1 protein, human; C515911:PAK3 protein, human; C515912:Pak3 protein, mouse