A groundbreaking study has unveiled a potential link between autism spectrum disorder (ASD) and impaired synaptic phagocytosis. Researchers have discovered that macrophages derived from individuals with ASD show reduced efficiency in clearing synaptosomes, which are fragments of neural connections. This dysfunction may contribute to the excessive number of dendritic spines observed in autistic brains, disrupting normal neural communication pathways. The research highlights the role of the CD209 gene in this process, suggesting it could serve as a molecular mediator for synaptic pruning deficits in ASD. By utilizing macrophages as substitutes for brain microglia, scientists have opened new avenues for understanding immune-synapse interactions in autism.

Autism spectrum disorder is characterized by challenges in social communication and repetitive behaviors, potentially linked to abnormalities in dendritic spines within the brain. Typically, during early development, the brain undergoes synaptic pruning, an essential process where unnecessary connections are removed to enhance neural efficiency. Microglia, the brain's immune cells, play a pivotal role in this pruning. However, studying their function in humans, particularly those with ASD, presents significant technical and ethical hurdles.

Innovative research conducted at Fujita Health University School of Medicine in Japan employed macrophages, immune cells derived from blood monocytes, to mimic the role of microglia. These macrophages were differentiated into two subtypes using colony-stimulating factors. The M-CSF-induced macrophages from typically developed individuals were found to be more adept at engulfing and clearing synaptosomes compared to GM-CSF-induced macrophages. Conversely, when sourced from individuals with ASD, these M-CSF macrophages exhibited a markedly diminished phagocytic ability, correlating with lower expression levels of the CD209 gene.

This discovery suggests that dysfunctional phagocytosis might underpin synaptic pruning deficiencies in ASD. Dr. Michihiro Toritsuka, lead author of the study, emphasized its significance in revealing the reduced phagocytosis capacity in ASD-associated macrophages. The findings align with previous studies indicating increased dendritic spine density and hyperconnectivity in autistic brains, providing direct evidence of impaired synaptic pruning activity in human immune cells outside the brain.

Dr. Manabu Makinodan highlighted the potential implications for drug discovery if similar impairments are identified in microglia. This research not only deepens our understanding of the immune-synapse interface in autism but also paves the way for therapies aimed at restoring proper phagocytic function. By identifying measurable impairments in macrophage function related to ASD, scientists have advanced a critical step toward unraveling the complexities of this neurodevelopmental condition.