Norepinephrine transporter knock-out alters expression of the genes connected with antidepressant drugs action
| Autor: | Kinga Szafran-Pilch, Joanna Solich, Paulina Pabian, Dariusz Zurawek, Magdalena Kolasa, Agata Faron-Górecka, Marta Dziedzicka-Wasylewska, M. Kusmider |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
hippocampus Hippocampus Pharmacology Mice Dopamine Internal medicine Desipramine medicine Animals Nerve Growth Factors Molecular Biology Mice Knockout Norepinephrine Plasma Membrane Transport Proteins biology Reverse Transcriptase Polymerase Chain Reaction General Neuroscience Dentate gyrus Neuropeptides Brain amygdala Tail suspension test Antidepressive Agents norepinephrine transporter knock-out mice microdissection TaqMan low density array Mice Inbred C57BL Endocrinology Monoamine neurotransmitter cortex Norepinephrine transporter biology.protein Antidepressant Neurology (clinical) Carrier Proteins Transcriptome Microdissection Developmental Biology medicine.drug |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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