Expression Profiling of a Genetic Animal Model of Depression Reveals Novel Molecular Pathways Underlying Depressive-Like Behaviours 英文参考文献.docVIP

ExpressionProfilingofaGeneticAnimalModelof DepressionRevealsNovelMolecularPathways UnderlyingDepressive-LikeBehaviours EkateriniBlaveri6,FionaKelly1,AlessandraMallei2,KrissHarris1,AdamTaylor1,JulietReid1 ,Maria Razzoli3,LuciaCarboni3,ChiaraPiubelli3,LauraMusazzi2,GirogioRacagni2,3,4,5,AleksanderMathe′4, MaurizioPopoli2,EnricoDomenici3,StewartBates1* 1Medicines Research Centre, GlaxoSmithKline, Stevenage, United Kingdom, 2Center of Neuropharmacology-Department of Pharmacological Sciences and Center of ExcellenceonNeurodegenerativeDiseases,UniversityofMilan,Milan,Italy,3NeurosciencesCEDD,GlaxoSmithKlineMedicinesResearchCentre,Verona,Italy,4Clinical Neuroscience–Psychiatry, Karolinska Insitutet, Huddinge Hospital, Stockholm, Sweden, 5Instituto Di Ricoverio e Cura a Carattere Scientifico, San Giovanni di Dio- Fatebenefratelli,Brescia,Italy,6CancerResearchUK,London,UnitedKingdom Abstract Background: The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemicalandpharmacologicalfeaturesconsistentwiththoseobservedinhumandepression. 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 animalsderivedfromthesamecolonysixmonthsapart,eachcohortstatisticallypoweredtoallowindependentaswellas 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 maintainedfeaturesofthemodel.Smallbutstatisticallysignificantincreaseswereconfirmedforcholinergic(chrm2,chrna7) andserotonergic receptors (Htr1a, Htr2a)in FSL ratsconsistent withknownneurochemical changes inth