Effects of antidepressant treatment on gene expression profile in mouse brain: cell type-specific transcription profiling using laser microdissection and microarray analysis.
A gene expression study of mice treated with the tricyclic antidepressant amitriptyline was performed. To enable the detection of cell type-specific expression changes, laser-microdissected nucleus accumbens was analysed after 4 and 28 days of treatment. After 4 days of treatment no significantly regulated genes could be detected in this study. In contrast, 95 genes exhibited different expression levels in animals treated for 28 days with amitrityline compared with sham animals. This observation reflects the long-term effects and adaptation processes observed in patients treated with this drug. Among the regulated genes are receptors belonging to the dopamine-dependent signalling cascade, ion channels (mainly voltage-dependent potassium and calcium channels) potentially involved in signalling cascades and neuropeptides. The results support the hypothesis that the therapeutic effect of this antidepressant is much more complex and not confined to a reuptake inhibition of neurotransmitters. Paradigms inducing only weak expression changes, which may be limited to certain cell types within the highly complex brain structure, can therefore be reliably investigated by applying a cell type-specific expression profiling technique based on laser microdissection and subsequent RNA amplification followed by DNA microarray analysis.
Böhm
C
C
AXARON Bioscience AG, Heidelberg, Germany.
Newrzella
D
D
Herberger
S
S
Schramm
N
N
Eisenhardt
G
G
Schenk
V
V
Sonntag-Buck
V
V
Sorgenfrei
O
O
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D007834:Lasers; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D042282:Microdissection; D009479:Neuropeptides / Q000235:genetics; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic
D000928:Antidepressive Agents; D007473:Ion Channels; D009479:Neuropeptides; D011956:Receptors, Cell Surface; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D000639:Amitriptyline