A tale of two transmitters: serotonin and histamine as in vivo biomarkers of chronic stress in mice
Year: 2022
Type: article
Abstract: Background Stress-induced mental illnesses (mediated by neuroinflammation) pose one of the world’s most urgent public health challenges. A reliable in vivo chemical biomarker of stress would significantly improve the clinical communities’ diagnostic and therapeutic approaches to illnesses, such as depression. Methods Male and female C57BL/6J mice underwent a chronic stress paradigm. We paired innovative in vivo serotonin and histamine voltammetric measurement technologies, behavioral testing, and cutting-edge mathematical methods to correlate chemistry to stress and behavior. Results Inflammation-induced increases in hypothalamic histamine were co-measured with decreased in vivo extracellular hippocampal serotonin in mice that underwent a chronic stress paradigm, regardless of behavioral phenotype. In animals with depression phenotypes, correlations were found between serotonin and the extent of behavioral indices of depression. We created a high accuracy algorithm that could predict whether animals had been exposed to stress or not based solely on the serotonin measurement. We next developed a model of serotonin and histamine modulation, which predicted that stress-induced neuroinflammation increases histaminergic activity, serving to inhibit serotonin. Finally, we created a mathematical index of stress, Si and predicted that during chronic stress, where Si is high, simultaneously increasing serotonin and decreasing histamine is the most effective chemical strategy to restoring serotonin to pre-stress levels. When we pursued this idea pharmacologically, our experiments were nearly identical to the model’s predictions. Conclusions This work shines the light on two biomarkers of chronic stress, histamine and serotonin, and implies that both may be important in our future investigations of the pathology and treatment of inflammation-induced depression.
Source: Journal of Neuroinflammation
Language: English
Subfield: Biological Psychiatry
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,390
Funders: Foundation for the National Institutes of Health, U.S. Department of Veterans Affairs, Simons Foundation, University of South Carolina, Wellcome Trust, National Institutes of Health, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, National Institute of Mental Health
Awards: G1745852896, G1949209965, Retroactive effect of dopamine on hippocampal spike timing-dependent plasticity, Dopamine-induced hippocampal plasticity: A synaptic model of foraging in mice, G265255789, G2863541165, Brain--inspired disinhihbitory learning rule for continual learning tasks in artificial neural networks, Memory across multiple time-scales, G4197035272, G4579492253, An In Vivo Voltammetric Serotonin Biomarker for Antidepressant Efficacy, G4960269386, G561957835, G5846511816, Plasticity of inhibitory synaptic transmission in the hippocampus, G6657520091, G7758880940, G7973444790, Memory across multiple time-scales, Voltammetric determination of neuronal serotonin and histamine co-regulation, G97620747
OpenAlex ID: W4283694772