TY - JOUR
T1 - Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours
AU - Blaveri, Ekaterini
AU - Kelly, Fiona
AU - Mallei, Alessandra
AU - Harris, Kriss
AU - Taylor, Adam
AU - Reid, Juliet
AU - Razzoli, Maria
AU - Carboni, Lucia
AU - Piubelli, Chiara
AU - Musazzi, Laura
AU - Racagni, Girogio
AU - Mathé, Aleksander
AU - Popoli, Maurizio
AU - Domenici, Enrico
AU - Bates, Stewart
N1 - Funding Information:
E Blaveri, S Bates, A Taylor, F Kelly, J Reid, K Harris, E Domenici, L Carboni, M Razzoli, C Piubelli are or were employees of GlaxoSmithKline and the study was partly funded by GlaxoSmithKline. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. None of the authors has patent applications on this work.
PY - 2010
Y1 - 2010
N2 - Background: The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression. Principal Findings: In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL) and control Flinders Depression Resistant (FRL) lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model. Small but statistically significant increases were confirmed for cholinergic (chrm2, chrna7) and serotonergic receptors (Htr1a, Htr2a) in FSL rats consistent with known neurochemical changes in the model. Much larger gene changes were validated in a number of novel genes as exemplified by TMEM176A, which showed 35-fold enrichment in the cortex and 30-fold enrichment in hippocampus of FRL animals relative to FSL. Conclusions: These data provide significant insights into the molecular differences underlying the Flinders model, and have potential relevance to broader depression research.
AB - Background: The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression. Principal Findings: In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL) and control Flinders Depression Resistant (FRL) lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model. Small but statistically significant increases were confirmed for cholinergic (chrm2, chrna7) and serotonergic receptors (Htr1a, Htr2a) in FSL rats consistent with known neurochemical changes in the model. Much larger gene changes were validated in a number of novel genes as exemplified by TMEM176A, which showed 35-fold enrichment in the cortex and 30-fold enrichment in hippocampus of FRL animals relative to FSL. Conclusions: These data provide significant insights into the molecular differences underlying the Flinders model, and have potential relevance to broader depression research.
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U2 - 10.1371/journal.pone.0012596
DO - 10.1371/journal.pone.0012596
M3 - Article
C2 - 20830301
AN - SCOPUS:77958521878
SN - 1932-6203
VL - 5
SP - 1
EP - 10
JO - PloS one
JF - PloS one
IS - 9
M1 - e12596
ER -