The metabolic regulator USF-1 is involved in the control of affective behaviour in mice

The metabolic regulator USF-1 is involved in the control of affective behaviour in mice

Epidemiological studies indicate a bidirectional association between metabolic disturbances, including obesity and related pathological states, and mood disorders, most prominently major depression. However, the biological mechanisms mediating the comorbid relationship between the deranged metabolic...

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Bibliographic Details
Published in:Translational psychiatry Vol. 12; no. 1; p. 497
Main Authors: Sideromenos, Spyros, Nikou, Maria, Czuczu, Barbara, Thalheimer, Nikolas, Gundacker, Anna, Horvath, Orsolya, Cuenca Rico, Laura, Stöhrmann, Peter, Niello, Marco, Partonen, Timo, Pollak, Daniela D.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01-12-2022
Nature Publishing Group
Subjects:
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Adult
Animals
Antidepressants
Anxiety
Anxiety Disorders
Automation
Behavior
Behavioral Sciences
Biological Psychology
Body fat
Brain
Circadian rhythm
Comorbidity
Depressive Disorder, Major
Emotional disorders
Experiments
Food
Hippocampus
Humans
Insulin
Medicine
Medicine & Public Health
Mental depression
Mental health
Metabolic disorders
Mice
Mice, Knockout
Mood disorders
Morphology
Neurogenesis
Neurosciences
Obesity
Pharmacology
Pharmacotherapy
Physiology
Psychiatry
Public health
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Summary:Epidemiological studies indicate a bidirectional association between metabolic disturbances, including obesity and related pathological states, and mood disorders, most prominently major depression. However, the biological mechanisms mediating the comorbid relationship between the deranged metabolic and mood states remain incompletely understood. Here, we tested the hypothesis that the enhanced activation of brown fat tissue (BAT), known to beneficially regulate obesity and accompanying dysfunctional metabolic states, is also paralleled by an alteration of affective behaviour. We used upstream stimulatory factor 1 (USF-1) knock-out (KO) mice as a genetic model of constitutively activated BAT and positive cardiometabolic traits and found a reduction of depression-like and anxiety-like behaviours associated with USF-1 deficiency. Surgical removal of interscapular BAT did not impact the behavioural phenotype of USF-1 KO mice. Further, the absence of USF-1 did not lead to alterations of adult hippocampal neural progenitor cell proliferation, differentiation, or survival. RNA-seq analysis characterised the molecular signature of USF-1 deficiency in the hippocampus and revealed a significant increase in the expression of several members of the X-linked lymphocyte-regulated (xlr) genes, including xlr3b and xlr4b . Xlr genes are the mouse orthologues of the human FAM9 gene family and are implicated in the regulation of dendritic branching, dendritic spine number and morphology. The transcriptional changes were associated with morphological alterations in hippocampal neurons, manifested in reduced dendritic length and complexity in USF-1 KO mice. Collectively these data suggest that the metabolic regulator USF-1 is involved in the control of affective behaviour in mice and that this modulation of mood states is unrelated to USF-1-dependent BAT activation, but reflected in structural changes in the brain.
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ISSN:2158-3188
2158-3188
DOI:10.1038/s41398-022-02266-5