دورية أكاديمية
Fluoxetine prevents development of an early stress-related molecular signature in the rat infralimbic medial prefrontal cortex. Implications for depression?
| العنوان: | Fluoxetine prevents development of an early stress-related molecular signature in the rat infralimbic medial prefrontal cortex. Implications for depression? |
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| المؤلفون: | Barreto Rafael A, Walker Frederick, Dunkley Peter R, Day Trevor A, Smith Doug W |
| المصدر: | BMC Neuroscience, Vol 13, Iss 1, p 125 (2012) |
| بيانات النشر: | BMC |
| سنة النشر: | 2012 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Neurotrophin, Gene expression, Microrarray, Restraint stress, Signalling pathways, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495 |
| الوصف: | Background Psychological stress, particularly in chronic form, can lead to mood and cognitive dysfunction and is a major risk factor in the development of depressive states. How stress affects the brain to cause psychopathologies is incompletely understood. We sought to characterise potential depression related mechanisms by analysing gene expression and molecular pathways in the infralimbic medial prefrontal cortex (ILmPFC), following a repeated psychological stress paradigm. The ILmPFC is thought to be involved in the processing of emotionally contextual information and in orchestrating the related autonomic responses, and it is one of the brain regions implicated in both stress responses and depression. Results Genome-wide microarray analysis of gene expression showed sub-chronic restraint stress resulted predominantly in a reduction in transcripts 24 hours after the last stress episode, with 239 genes significantly decreased, while just 24 genes had increased transcript abundance. Molecular pathway analysis using DAVID identified 8 pathways that were significantly enriched in the differentially expressed gene list, with genes belonging to the brain-derived neurotrophic factor – neurotrophin receptor tyrosine kinase 2 (BDNF-Ntrk2) pathway most enriched. Of the three intracellular signalling pathways that are downstream of Ntrk2, real-time quantitative PCR confirmed that only the PI3K-AKT-GSK3B and MAPK/ERK pathways were affected by sub-chronic stress, with the PLCγ pathway unaffected. Interestingly, chronic antidepressant treatment with the selective serotonin reuptake inhibitor, fluoxetine, prevented the stress-induced Ntrk2 and PI3K pathway changes, but it had no effect on the MAPK/ERK pathway. Conclusions These findings indicate that abnormal BDNF-Ntrk2 signalling may manifest at a relatively early time point, and is consistent with a molecular signature of depression developing well before depression-like behaviours occur. Targeting this pathway prophylactically, particularly in ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1471-2202 |
| العلاقة: | http://www.biomedcentral.com/1471-2202/13/125Test; https://doaj.org/toc/1471-2202Test; https://doaj.org/article/d15c70d3bb5e4ee2bc7d895f6abf8944Test |
| DOI: | 10.1186/1471-2202-13-125 |
| الإتاحة: | https://doi.org/10.1186/1471-2202-13-125Test https://doaj.org/article/d15c70d3bb5e4ee2bc7d895f6abf8944Test |
| رقم الانضمام: | edsbas.BCBDCE6E |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14712202 |
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| DOI: | 10.1186/1471-2202-13-125 |