With regard the pattern of gene expression, we found the vast maj

With regard the pattern of gene expression, we found the vast major ity of differentially expressed genes were down regulated, with most of the up regulated transcripts being predicted genes or pseudogenes. Down regulation of a majority of genes in the PFC has also been observed following Erlotinib molecular weight chronic stress. To improve interpretability of the microarray data in relation to gene function in biological processes, we carried out pathway analysis whereby the degree to which sets of genes belonging to a priori deter mined biological pathways were enriched in the differen tially expressed gene list was assessed using DAVID. We identified eight significantly enriched pathways, three had FDRs less than 10% Inhibitors,Modulators,Libraries and we focussed on these. Notably, all three of these pathways have been implicated in neuropsychiatric disorders.

The most significantly enriched pathway, and the one with the lowest FDR, was for neurotrophin signalling. There is a substantial body of evidence implicating BDNF in MDD. For example, BDNF and Ntrk2 tran scripts and Inhibitors,Modulators,Libraries protein levels were markedly reduced in the PFC and amygdala of MDD subjects. Also, serum BDNF is lower in MDD sufferers and BDNF is being considered a predictive diagnostic marker for MDD. Additionally, a number of chronic stress based animal models of MDD have shown perturbation Inhibitors,Modulators,Libraries in the BDNF Ntrk2 signalling pathway in various brain regions. Indeed, Nestler and colleagues have demonstrated a cru cial role for BDNF in the mesolimbic system for the de velopment of depression like behaviour.

We did not find stress induced change in BDNF transcript levels in ILmPFC, which may imply that BDNF protein levels are also unchanged. Inhibitors,Modulators,Libraries This raises the question as to why Ntrk2 levels should change if BDNF does not. One pos sibility is that BDNF protein is delivered by dopamin ergic afferents to the ILmPFC and, consistent with this notion, Inhibitors,Modulators,Libraries we have found increased BDNF tran script levels in VTA dopamine neurons. Alteration in the BDNF pathway can also be observed in some acute stress models, however as mentioned above, these changes are typically short lived. Our altered BDNF Ntrk2 pathway finding was evident at 24 hours post the last stress episode of the sub chronic stress paradigm and is consistent with a molecular signature of depression.

The sub chronic stress paradigm used in the present study does not in duce depression like behaviours, therefore, this molecu http://www.selleckchem.com/products/17-AAG(Geldanamycin).html lar finding may represent an early mechanistic indicator of depression neuropathology. Prevention of the sub chronic stress induced BDNF Ntrk2 perturbation by the antidepressant, fluoxetine, is consistent with this notion. Furthermore, it may also indicate that the ILmPFC is a particularly sensitive region to stress and therefore im portant in the development of the depressive state.

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>