NDLI: Editing of AMPA and Serotonin 2C Receptors in Individual Central Neurons, Controlling Wakefulness

Content Provider	Springer Nature Link
Author	Sergeeva, Olga A. Amberger, Bettina T. Haas, Helmut L.
Copyright Year	2007
Abstract	(1) Pre-mRNA editing of serotonin 2C (5-HT2C) and glutamate (Glu) receptors (R) influences higher brain functions and pathological states such as epilepsy, amyotrophic lateral sclerosis, and depression. Adenosine deaminases acting on RNA (ADAR1–3) convert adenosine to inosine on synthetic RNAs, analogous to 5-HT2cR and GluR. The order of editing as well as mechanisms controlling editing in native neurons is unknown. (2) With single-cell RT-PCR we investigated the co-expression of ADAR genes with GluR and 5-HT2CR and determined the editing status at known sites in the hypothalamic tuberomamillary nucleus, a major center for wakefulness and arousal. (3) The most frequently expressed enzymes were ADAR1, followed by ADAR2. The Q/R site of GluR2 was always fully edited. Editing at the R/G site in the GluR2 (but not GluR4) subunit was co-ordinated with ADAR expression: maximal editing was found in neurons expressing both ADAR2 splice variants of the deaminase domain and lacking ADAR3. (4) Editing of the 5-HT2CR did not correlate with ADAR expression. The 5-HT2CR mRNA was always edited at A, in the majority of cells at B sites and variably edited at E, C and D sites. A negative correlation was found between editing of C and D sites. The GluR4 R/G site editing was homogeneous within individuals: it was fully edited in all neurons obtained from 12 rats and under-edited in six neurons obtained from three rats. (5) We conclude that GluR2 R/G editing is controlled at the level of ADAR2 and therefore this enzyme may be a target for pharmacotherapy. On the other hand, further factors/enzymes besides ADAR must control or influence 5-HT2CR and GluR pre-mRNA editing in native neurons; our data indicate that these factors vary between individuals and could be predictors of psychiatric disease.
Starting Page	669
Ending Page	680
Page Count	12
File Format	PDF
ISSN	02724340
Journal	Cellular and Molecular Neurobiology
Volume Number	27
Issue Number	5
e-ISSN	15736830
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2007-06-07
Publisher Place	New York
Access Restriction	Subscribed
Subject Keyword	Adenosine deaminase acting at RNA Serotonin Glutamate Histamine Single-cell RT-PCR Animal Anatomy / Morphology / Histology Neurosciences
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Cellular and Molecular Neuroscience

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