Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours
| Autor: | Maria Razzoli, Kriss Harris, Chiara Piubelli, Juliet Reid, Alessandra Mallei, Maurizio Popoli, Enrico Domenici, Ekaterini Blaveri, Aleksander A. Mathé, Adam Taylor, Stewart Bates, Lucia Carboni, Girogio Racagni, Fiona M. Kelly, Laura Musazzi |
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| Přispěvatelé: | Blaveri E., Kelly F., Mallei A., Harris K., Taylor A., Reid J., Razzoli M., Carboni L., Piubelli C., Musazzi L., Racagni G., Mathé A., Popoli M., Domenici E., Bates S., Blaveri, E, Kelly, F, Mallei, A, Harris, K, Taylor, A, Reid, J, Razzoli, M, Carboni, L, Piubelli, C, Musazzi, L, Racagni, G, Mathé, A, Popoli, M, Domenici, E, Bates, S |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
prefrontal-frontal cortex CHOLINERGIC RECEPTOR Rat model lcsh:Medicine Biology Animals Behavior Animal Depression Disease Models Animal Humans Rats Gene Expression Profiling Animal model Neurochemical genome-wide microarray FLINDERS RAT REAL-TIME PCR lcsh:Science Depression (differential diagnoses) Genetics Behavior Multidisciplinary Animal hippocampu Mental Health/Mood Disorders SEROTONERGIC RECEPTOR lcsh:R Neuroscience/Animal Cognition Gene expression profiling MICROARRAY EXPRESSION PROFILING Genetics and Genomics/Disease Models Disease Models lcsh:Q DNA microarray Neuroscience Research Article |
| Zdroj: | PLoS ONE, Vol 5, Iss 9, p e12596 (2010) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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