Deciphering the Metabolome under Stress: Insights from Rodent Models

Abstract

Despite intensive research efforts to understand the molecular underpinnings of psychological stress and stress responses, the underlying molecular mechanisms remain largely elusive. Towards this direction, a plethora of stress rodent models have been established to investigate the effects of exposure to different stressors. To decipher affected molecular pathways in a holistic manner in these models, metabolomics approaches addressing altered, small molecule signatures upon stress exposure in a high-throughput, quantitative manner provide insightful information on stress-induced systemic changes in the brain. In this review, we discuss stress models in mice and rats, followed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) metabolomics studies. We particularly focus on acute, chronic and early life stress paradigms, highlight how stress is assessed at the behavioral and molecular levels and focus on metabolomic outcomes in the brain and peripheral material such as plasma and serum. We then comment on common metabolomics patterns across different stress models and underline the need for unbiased -omics methodologies and follow-up studies of metabolomics outcomes to disentangle the complex pathobiology of stress and pertinent psychopathologies.

Thematic Selection: Stress and Stress-related Disorders Neurobiology & Translational Aspects of Stress-related Disorders (Part 3)

“…Kyriatzis et al review current findings on the involvement of the neurotensinergic system in stress response and the pathophysiology of stress-related disorders, with an emphasis on gene, mRNA, and protein alterations, behavioral and pharmacological studies and therapeutic implementations [ 7 ]. Providing insights from mass spectrometry and nuclear magnetic resonance metabolomic studies in rodent models, Papageorgiou et al investigate affected molecular pathways upon stress exposure and provide insightful information on stress-induced systemic changes in the brain and the periphery [ 8 ]. The review article by MacKay et al focuses on the role of the gut-immune-brain axis, the human microbiome and the therapeutic potential of pro and prebiotics in stress-related disorders [ 9 ].…”