title: Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours.
abstract: 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.
authors.affiliation: Cancer Research UK, London, United Kingdom.
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Blaveri
authors.forename: Fiona
authors.initials: F
authors.lastname: Kelly
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mallei
authors.forename: Kriss
authors.initials: K
authors.lastname: Harris
authors.forename: Adam
authors.initials: A
authors.lastname: Taylor
authors.forename: Juliet
authors.initials: J
authors.lastname: Reid
authors.forename: Maria
authors.initials: M
authors.lastname: Razzoli
authors.forename: Lucia
authors.initials: L
authors.lastname: Carboni
authors.forename: Chiara
authors.initials: C
authors.lastname: Piubelli
authors.forename: Laura
authors.initials: L
authors.lastname: Musazzi
authors.forename: Girogio
authors.initials: G
authors.lastname: Racagni
authors.forename: Aleksander
authors.initials: A
authors.lastname: Mathé
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
authors.forename: Enrico
authors.initials: E
authors.lastname: Domenici
authors.forename: Stewart
authors.initials: S
authors.lastname: Bates
mesh_terms: 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