# Brain Monoamine Deficits in the CD Mouse Model of Williams–Beuren Syndrome

## TL;DR

This study finds brain monoamine deficits in a mouse model of Williams–Beuren Syndrome, which may explain the behavioral issues seen in the condition.

## Contribution

The study identifies specific monoaminergic system alterations in CD mice, providing new insights into the neurobiological basis of Williams–Beuren Syndrome.

## Key findings

- Dopamine levels were reduced in the nucleus accumbens of CD mice.
- Serotonin and its metabolites were decreased in the hypothalamus of CD mice.
- Altered correlations between monoamine systems were observed in multiple brain regions of CD mice.

## Abstract

Williams–Beuren Syndrome (WBS) is a rare neurodevelopmental disease caused by a microdeletion on chromosome 7 (7q11.23) and associated with behavioral disorders such as hypersociability, impaired visuospatial memory, anxiety, and motor disorders. The precise underlying neurobiological bases remain unknown. The CD mouse is a genetic model that reproduces the deletion found in WBS patients on the equivalent mouse locus. Taking into account that monoaminergic systems are known to modulate behaviors that are altered in WBS, we hypothesized that CD mice could present quantitative and qualitative changes in brain noradrenaline, dopamine, and serotonin systems compared to wild-type (WT) littermates. We sampled 10 brain regions in female mice for quantifying monoamines and related compounds by high-performance liquid chromatography coupled to electrochemical detection. We found a decrease in dopamine in the nucleus accumbens and serotonin and its metabolites in the hypothalamus. Using correlative approaches of tissue content across the brain, we found that the relationships between neurotransmitters or their metabolic ratios (metabolite/neurotransmitter) changed in CD compared to WT. Notably, compared to WT, the ratios in CD mice showed striatal correlations for the serotonin/dopamine systems interaction, and cortical, thalamic, and hypothalamic correlations for the noradrenaline/dopamine systems interaction. The data suggest specific alterations of monoaminergic systems across the brain that could sustain the abnormal behavioral responses displayed by CD mice.