RT Journal Article
SR Electronic
T1 A Resting-State Functional MR Imaging and Spectroscopy Study of the Dorsal Hippocampus in the Chronic Unpredictable Stress Rat Model
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3640
OP 3650
DO 10.1523/JNEUROSCI.2192-18.2019
VO 39
IS 19
A1 Ricardo Magalhães
A1 Ashley Novais
A1 David A. Barrière
A1 Paulo Marques
A1 Fernanda Marques
A1 João C. Sousa
A1 João J. Cerqueira
A1 Arnaud Cachia
A1 Therese M. Jay
A1 Michel Bottlaender
A1 Nuno Sousa
A1 Sébastien Mériaux
A1 Fawzi Boumezbeur
YR 2019
UL http://www.jneurosci.org/content/39/19/3640.abstract
AB Exposure to chronic stress leads to an array of anatomical, functional, and metabolic changes in the brain that play a key role in triggering psychiatric disorders such as depression. The hippocampus is particularly well known as a target of maladaptive responses to stress. To capture stress-induced changes in metabolic and functional connectivity in the hippocampus, stress-resistant (low-responders) or -susceptible (high-responders) rats exposed to a chronic unpredictable stress paradigm (categorized according to their hormonal and behavioral responses) were assessed by multimodal neuroimaging; the latter was achieved by using localized 1H MR spectroscopy and resting-state functional MRI (fMRI) at 11,7T data from stressed (n = 25) but also control (n = 15) male Wistar rats.Susceptible animals displayed increased GABA–glutamine (+19%) and glutamate–glutamine (+17%) ratios and decreased levels of macromolecules (−11%); these changes were positively correlated with plasma corticosterone levels. In addition, the neurotransmitter levels showed differential associations with functional connectivity between the hippocampus and the amygdala, the piriform cortex and thalamus between stress-resistant and -susceptible animals. Our observations are consistent with previously reported stress-induced metabolomic changes that suggest overall neurotransmitter dysfunction in the hippocampus. Their association with the fMRI data in this study reveals how local adjustments in neurochemistry relate to changes in the neurocircuitry of the hippocampus, with implications for its stress-associated dysfunctions.SIGNIFICANCE STATEMENT Chronic stress disrupts brain homeostasis, which may increase the vulnerability of susceptible individuals to neuropsychiatric disorders such as depression. Characterization of the differences between stress-resistant and -susceptible individuals on the basis of noninvasive imaging tools, such as magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI), contributes to improved understanding of the mechanisms underpinning individual differences in vulnerability and can facilitate the design of new diagnostic and intervention strategies. Using a combined functional MRI/MRS approach, our results demonstrate that susceptible- and non-susceptible subjects show differential alterations in hippocampal GABA and glutamate metabolism that, in turn, associate with changes in functional connectivity.