+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

The identification of metabolic disturbances in the prefrontal cortex of the chronic restraint stress rat model of depression



The identification of metabolic disturbances in the prefrontal cortex of the chronic restraint stress rat model of depression



Behavioural Brain Research 305: 148-156



Major depressive disorder, with serious impairment in cognitive and social functioning, is a complex psychiatric disorder characterized by pervasive and persistent low mood and a loss of interest or pleasure. However, the underlying molecular mechanisms of depression remain largely unknown. In this study, we used a non-targeted metabolomics approach based on gas chromatography-mass spectrometry of the prefrontal cortex in chronic restraint stress (CRS)-treated rats. CRS was induced in the stress group by restraining rats in a plastic restrainer for 6h every day. This stress paradigm continued for 21 days. Body weight measurement and behavior tests were applied, including the sucrose preference test for anhedonia, the forced swimming test for despair-like behavior, and open field test and the elevated plus-maze to test for anxiety-like behaviors in rats after CRS. Differentially expressed metabolites associated with CRS-treated rats were identified by combining multivariate and univariate statistical analysis and corrected for multiple testing using the Benjamini-Hochberg procedure. A heat map of differential metabolites was constructed using Matlab. Ingenuity Pathways Analysis was applied to identify the predicted pathways and biological functions relevant to the bio-molecules of interest. Our findings showed that CRS induces depression-like behaviors and not anxiety-like behaviors. Thirty-six metabolites were identified as potential depression biomarkers involved in amino acid metabolism, energy metabolism and lipid metabolism, as well as a disturbance in neurotransmitters. Consequently, this study provides useful insights into the molecular mechanisms of depression.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 059073902

Download citation: RISBibTeXText

PMID: 26947756

DOI: 10.1016/j.bbr.2016.03.005


Related references

Disrupted MEK/ERK signaling in the medial orbital cortex and dorsal endopiriform nuclei of the prefrontal cortex in a chronic restraint stress mouse model of depression. Neuroscience Letters 580: 163-168, 2015

Metabolomic analysis reveals metabolic disturbances in the prefrontal cortex of the lipopolysaccharide-induced mouse model of depression. Behavioural Brain Research 308: 115-127, 2016

Effect of Acupuncture on Expression of Glial Fibrillary Acidic Protein in Hippocampus and Prefrontal Cortex and Serum Interleukin-10 in Chronic Restraint Stress Depression Rats. Zhen Ci Yan Jiu 43(4): 209-214, 2018

Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex. Progress in Neuro-Psychopharmacology & Biological Psychiatry 39(1): 112-119, 2013

Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression. Frontiers in Cellular Neuroscience 12: 24-24, 2018

Effects of chronic restraint stress on dopamine release in the medial prefrontal cortex of the rat. Society for Neuroscience Abstracts 22(1-3): 2058, 1996

Differential expression of synaptic proteins after chronic restraint stress in rat prefrontal cortex and hippocampus. Brain Research 1385: 26-37, 2012

Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery. Neuroscience 164(2): 798-808, 2010

Chronic restraint stress increases the protein expression of VEGF and its receptor VEGFR-2 in the prefrontal cortex. Synapse 69(4): 190-194, 2015

Targeted Metabolomic Pathway Analysis and Validation Revealed Glutamatergic Disorder in the Prefrontal Cortex among the Chronic Social Defeat Stress Mice Model of Depression. Journal of Proteome Research 15(10): 3784-3792, 2016

Amino acid metabolic dysfunction revealed in the prefrontal cortex of a rat model of depression. Behavioural Brain Research 278: 286-292, 2015

Proteomics reveals energy and glutathione metabolic dysregulation in the prefrontal cortex of a rat model of depression. Neuroscience 247: 191-200, 2014

Establishment of a chronic restraint stress model of depression with C57BL/6J mice. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae 37(1): 8-11, 2015

Prefrontal Cortex GABAergic Deficits and Circuit Dysfunction in the Pathophysiology and Treatment of Chronic Stress and Depression. Current Opinion in Behavioral Sciences 14(): 1-8, 2016

Neuropeptide Y: identification of a novel rat mRNA splice-variant that is downregulated in the hippocampus and the prefrontal cortex of a depression-like model. Peptides 35(1): 49-55, 2012