Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours.
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.


RESULTS
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.
Blaveri
Ekaterini
E
Cancer Research UK, London, United Kingdom.
Kelly
Fiona
F
Mallei
Alessandra
A
Harris
Kriss
K
Taylor
Adam
A
Reid
Juliet
J
Razzoli
Maria
M
Carboni
Lucia
L
Piubelli
Chiara
C
Musazzi
Laura
L
Racagni
Girogio
G
Mathé
Aleksander
A
Popoli
Maurizio
M
Domenici
Enrico
E
Bates
Stewart
S
D000818:Animals; D001522:Behavior, Animal; D003863:Depression / Q000235:genetics* / Q000378:metabolism / Q000523:psychology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051381:Rats