title: Altered metabolic activity in the developing brain of rats predisposed to high versus low depression-like behavior.
abstract: Individual differences in human temperament can increase the risk of psychiatric disorders like depression and anxiety. Our laboratory utilized a rat model of temperamental differences to assess neurodevelopmental factors underlying emotional behavior differences. Rats selectively bred for low novelty exploration (Low Responders, LR) display high levels of anxiety- and depression-like behavior compared to High Novelty Responder (HR) rats. Using transcriptome profiling, the present study uncovered vast gene expression differences in the early postnatal HR versus LR limbic brain, including changes in genes involved in cellular metabolism. These data led us to hypothesize that rats prone to high (versus low) anxiety/depression-like behavior exhibit distinct patterns of brain metabolism during the first weeks of life, which may reflect disparate patterns of synaptogenesis and brain circuit development. Thus, in a second experiment we examined activity of cytochrome C oxidase (COX), an enzyme responsible for ATP production and a correlate of metabolic activity, to explore functional energetic differences in the HR/LR early postnatal brain. We found that HR rats display higher COX activity in the amygdala and specific hippocampal subregions compared to LRs during the first 2 weeks of life. Correlational analysis examining COX levels across several brain regions and multiple early postnatal time points suggested desynchronization in the developmental timeline of the limbic HR versus LR brain during the first two postnatal weeks. These early divergent COX activity levels may reflect altered circuitry or synaptic activity in the early postnatal HR/LR brain, which could contribute to the emergence of their distinct behavioral phenotypes.
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, 1720 7th Ave S., SC 745, University of Alabama-Birmingham AL, USA.
authors.forename: Chelsea R
authors.initials: CR
authors.lastname: McCoy
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, 1720 7th Ave S., SC 745, University of Alabama-Birmingham AL, USA.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Golf
authors.affiliation: Department of Surgery, 1600 7 Ave S., ACC300, University of Alabama-Birmingham, AL, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Melendez-Ferro
authors.affiliation: Department of Pediatrics, 1600 7 Ave S., ACC502, University of Alabama-Birmingham, AL, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Perez-Costas
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, 1720 7th Ave S., SC 745, University of Alabama-Birmingham AL, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Glover
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, 1720 7th Ave S., SC 745, University of Alabama-Birmingham AL, USA.
authors.forename: Nateka L
authors.initials: NL
authors.lastname: Jackson
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, 1720 7th Ave S., SC 745, University of Alabama-Birmingham AL, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Stringfellow
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, 1720 7th Ave S., SC 745, University of Alabama-Birmingham AL, USA.
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Pugh
authors.affiliation: Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill 27599, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Fant
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, 1720 7th Ave S., SC 745, University of Alabama-Birmingham AL, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Clinton
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D003866:Depressive Disorder / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D008297:Male; D010551:Personality / Q000502:physiology; D025341:Principal Component Analysis; D017207:Rats, Sprague-Dawley
chemical_list: D003576:Electron Transport Complex IV
keywords: amygdala; anxiety; cytochrome C oxidase; metabolism; neurodevelopment; transcriptome