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A recent study published on April 1 in the open-access journal PLOS Biology reveals insights into the mechanisms behind autism symptoms in mice. Researchers from Wenzhou Medical University and Xiamen University, led by Dongdong Zhao and Yun-wu Zhang, identified a disruption in the balance between two nerve proteins as a contributing factor.
Autism Spectrum Disorder (ASD) affects roughly 1% of the global population, manifesting in a range of social and cognitive challenges. Although prior studies have pinpointed various genetic elements tied to ASD, particularly those involved in neuronal function, the precise connections remain ambiguous. The focal point of this study is the evaluation of two neuronal proteins that may influence ASD symptoms.
One key protein, MDGA2, plays a significant role in nerve signal transmission, with certain mutations in its gene previously linked to ASD in humans. The researchers found that mice with lowered MDGA2 levels displayed behaviors characteristic of ASD, such as excessive grooming and impaired social interaction. Additionally, these mice demonstrated heightened activity in select nerve synapses and elevated levels of BDNF, a protein affiliated with ASD that operates through the stimulation of the TrkB protein. Interestingly, administering a synthetic peptide that mimicked MDGA2 and inhibited BDNF/TrkB signaling resulted in a reduction of the observed symptoms.
The findings suggest a competitive relationship between MDGA2 and BDNF for binding to TrkB sites, with disturbances in this dynamic potentially leading to altered neuronal activity characteristic of ASD. The researchers propose that targeting this protein interaction could offer new avenues for treatment development, although more research is needed to fully elucidate the functions of this system and its implications for ASD symptoms.
According to Yun-wu Zhang, “While mutations in the MDGA2 gene are known to lead to autism spectrum disorders (ASD), the mechanisms involved were not well understood. Our study uncovers a crucial function of MDGA2 in regulating BDNF/TrkB signaling, which is essential for normal excitatory neuronal activity. The absence of MDGA2 leads to abnormal activation of BDNF/TrkB, resulting in increased excitatory neuronal activity and ASD-like traits in mice.”
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