title: Down-regulation of GluK2 kainate receptor expression by chronic treatment with mood-stabilizing anti-convulsants or lithium in cultured astrocytes and brain, but not in neurons.
abstract: Recent studies have indicated that glutamatergic transmission may be altered in bipolar disorder and affected by chronic treatment with mood-stabilizing drugs. Kainate receptors may be of special interest because i) they have a modulatory role in synaptic transmission, long-term potentiation (LTP) and long-term depression (LDP); and ii) involvement of the kainate receptor subunit GluK2 (GluR6) in behavioral symptoms thought characteristic of mania has been demonstrated in knock-out mice. Glutamate receptors are expressed not only on neurons, but also on astrocytes, where they contribute to regulation of synaptic activity. We have previously shown that primary cultures of mouse astrocytes respond to chronic but not acute treatment with therapeutic relevant concentrations of any of the 'classical' mood-stabilizing drugs, lithium ion (Li(+)), carbamazepine or valproate, with changes in uptake of myo-inositol, cPLA(2) expression and intracellular pH. In the present work, we found i) similar gene expression of the GluK2 subunit of the kainate receptor family in primary cultures of mouse astrocytes and in brain in vivo; ii) a reduction of mRNA and protein expression of GluK2 in astrocytes and in brain after chronic treatment with carbamazepine but no effect in neurons; iii) similar down-regulation in astrocytes by oxcarbamazepine, valproic acid or Li(+), which all have mood-stabilizing effect, but not by the anti-convulsant topiramate, which has no such activity; and iv) abrogation of a normally occurring glutamate-induced ERK phosphorylation in the cultured astrocytes after chronic treatment with any of the mood-stabilizing drugs mentioned above. Possible relationships between these and previously demonstrated effects are discussed.
authors: Department of Clinical Pharmacology, China Medical University, Shenyang, PR China.
authors: Baoman
authors: B
authors: Li
authors: Shiquen
authors: S
authors: Zhang
authors: Min
authors: M
authors: Li
authors: Hongyan
authors: H
authors: Zhang
authors: Leif
authors: L
authors: Hertz
authors: Liang
authors: L
authors: Peng
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D054022:Cerebrum / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018020:Lithium Compounds / Q000494:pharmacology; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism*; D000097806:GluK2 Kainate Receptor
chemical_list: D000927:Anticonvulsants; D048049:Extracellular Signal-Regulated MAP Kinases; D018020:Lithium Compounds; D011619:Psychotropic Drugs; D012333:RNA, Messenger; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor