title: Norepinephrine transporter knock-out alters expression of the genes connected with antidepressant drugs action.
abstract: Norepinephrine transporter knock-out mice (NET-KO) exhibit depression-resistant phenotypes. They manifest significantly shorter immobility times in both the forced swim test and the tail suspension test. Moreover, biochemical studies have revealed the up-regulation of other monoamine transporters (dopamine and serotonin) in the brains of NET-KO mice, similar to the phenomenon observed after the chronic pharmacological blockade of norepinephrine transporter by desipramine in wild-type (WT) animals. NET-KO mice are also resistant to stress, as we demonstrated previously by measuring plasma corticosterone concentration. In the present study, we used a microdissection technique to separate target brain regions and the TaqMan Low Density Array approach to test the expression of a group of genes in the NET-KO mice compared with WT animals. A group of genes with altered expression were identified in four brain structures (frontal and cingulate cortices, dentate gyrus of hippocampus and basal-lateral amygdala) of NET-KO mice compared with WT mice. These genes are known to be altered by antidepressant drugs administration. The most interesting gene is Crh-bp, which modulates the activity of corticotrophin--releasing hormone (CRH) and several CRH-family members. Generally, genetic disturbances within noradrenergic neurons result in biological changes, such as in signal transduction and intercellular communication, and may be linked to changes in noradrenaline levels in the brains of NET-KO mice.
authors.affiliation: Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland. Electronic address: solich@if-pan.krakow.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Solich
authors.affiliation: Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kolasa
authors.affiliation: Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kusmider
authors.affiliation: Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Faron-Gorecka
authors.affiliation: Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Pabian
authors.affiliation: Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Zurawek
authors.affiliation: Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Szafran-Pilch
authors.affiliation: Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Dziedzicka-Wasylewska
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D042282:Microdissection; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D000928:Antidepressive Agents; D002352:Carrier Proteins; D009414:Nerve Growth Factors; D009479:Neuropeptides; D050484:Norepinephrine Plasma Membrane Transport Proteins; C067133:corticotropin releasing factor-binding protein
keywords: Amygdala; Cortex; Hippocampus; Microdissection; Norepinephrine transporter knock-out mice; TaqMan low density array