Ученые связали синдром беспокойных ног с мутацией гена MEIS1 и нарушением работы мозжечка

Researchers have identified a specific brain region and gene mutation that may contribute to the abnormal movement patterns associated with RLS. Key takeaways: - A recent study using larval zebrafish identified a link between the MEIS1 gene and abnormal movement patterns similar to restless legs syndrome. - Researchers found that mutations in this gene led to a partial loss of Purkinje cells in the cerebellum, disrupting downstream neuron activity. - Medications commonly prescribed for restless legs syndrome were shown to normalize the behavior of the mutant zebrafish, suggesting potential pathways for future targeted therapies. A new study published in Current Biology suggests that the cerebellum may play a crucial role in the development and function of restless legs syndrome (RLS). Using larval zebrafish as a model organism, researchers at the University of Basel discovered that a specific gene associated with RLS affects both brain development and movement patterns. “Studies in humans have implicated many different brain regions, but it remains unclear how they relate to RLS,” says Alex Schier, PhD, professor at the Biozentrum of the University of Basel, in a release. “Our work highlights possible contributions from the cerebellum, a brain region crucial for coordinating movement.” The project began as an effort to understand the genetics of human sleep-related disorders. “Previous studies identified genes associated with RLS symptoms in humans, but their neuronal and behavioral functions were unclear,” says first author William Joo, a postdoctoral fellow, in a release. Upon analyzing several genes, the research team found that mutating the MEIS1 gene significantly altered the movement patterns of the zebrafish larvae. Typically, zebrafish move in a “burst and glide” pattern, consisting of swimming, pausing, and swimming again. However, in the MEIS1 mutant zebrafish, these bouts of movement became much longer, prompting researchers to look for structural or activity-based differences in the brain. The team observed developmental abnormalities in the cerebellum of the mutant zebrafish, specifically affecting Purkinje cells. These prominent neurons are responsible for suppressing the activity of other neurons to help coordinate movement. “This cell type is partially lost in the cerebellum of zebrafish mutants,” says Joo in a release. “Our results indicate that the activity of downstream neurons becomes perturbed when the Purkinje cells are missing, and that this is what generates abnormal locomotion patterns in the mutant larvae.” When the researchers administered medications commonly prescribed to treat RLS, they found that the drugs normalized the behavior of the mutant fish. The study raises the possibility that other RLS risk genes may play similar roles in brain development and movement. “Zebrafish have provided great insights into the functions of this RLS-related gene,” says Schier in a release. “But future studies must further investigate whether the same brain region and mechanisms are also relevant in RLS patients.” According to the researchers, these findings could eventually support the development of more effective treatments and improve RLS diagnoses, which currently rely almost entirely on patient-reported symptoms.