Study altered bonds synaptic to autism

Autistic spectrum disorder (ASD) is a complex neurological development condition in which affected people experience difficulties in social communication and exhibit restricted and repetitive patterns of behavior or interests. A growing research body suggests that neurobiological changes, particularly abnormalities in dendritic spines, small bumps in nerve cells where synapses are formed, can be a distinctive seal of ASD. In particular, studies have found an unusually high number of these thorns in individuals with autism. This excess of synaptic connections could alter the normal communication routes in the brain, which can contribute to the behavioral and cognitive characteristics observed in the TEA.

In normal circumstances, the brain suffers synaptic pruning, a process that implies the elimination of unnecessary or weak synaptic connections to give way to more efficient neuronal networks. This pruning is crucial during early development and adolescence. Microglia, immune cells resident in the brain, play a fundamental role in this process. In addition to defending the brain against infection or injuries, they act as gardeners when cutting excess synapses to help shape healthy neuronal circuits. However, studying how microglia work in the human brain, especially in individuals with autism, has been difficult. Unlike animal models, observe and measure directly the microglial activity in living humans raises technical and ethical challenges, leaving many questions about their precise role in the ASD without response.

To study ASD related mechanisms, researchers used immune cells of macrophages derived from blood-as monocytes for cerebral microglia. Then, they differentiated macrophages in two subtypes using specific colon-stimulation factors (CSF): LCC of granulocytes-macrophages (GM-CSF) induced a pro-inflammatory phenotype “similar to M1”, while the macrophage recs (M-CSF) induced a phenotype “similar to m2” associated with the repair of titles and The immunic titles. To evaluate the ability of macrophages to clean the synaptic material, researchers introduced fragments of synoptosomes of neuronal connections generated by pluripotent stem cells induced by humans (HIPSC). The study that implies the innovative results was published online in the Molecular Magazine Psychiatry on April 4, 2025.

The study found that macrophages induced by M-CSF (M-CSF Mφ) of typically developed individuals were more efficient in macrophages induced by phagocytosis and cleaning of synaptosomas, compared to macrophages induced by GM-CSF (GM-CSF Mφ). However, when it was derived from individuals with ASD, the M-CSF Mφ exhibited a significantly reduced capacity to perform phagocytosis. This deterioration in synaptic phagocytosis was associated with a lower expression of the CD209 gene, which can play a critical role in the ability of macrophages for phagocytous synaptic proteins. These findings suggest that dysfunctional phagocytosis could contribute to synaptic pruning deficits observed in ASD, with the CD209 gene that potentially serves as a molecular mediator.

“This Study is the first to reveal Lower Phagocytosis capacity of synaptosomes in asd-m-csf macrophages compared to typically developed-m-csf macrophages, with a correlation to cd209 gene expression,” Said Dr. Michihiro Toritsuka Professor at the Division of Transformative Psychiatry and Synergistic Research, International Center for Brain Science, Fujita Health University School of Medicine, Japan, and Lead Author of the Study.

This pioneer research adds to a growing body of evidence that implies immune dysfunction in the alterations of the neurological development of ASD. While previous post -mortem and images studies have reported a greater density of the dendritic column and hyperconnectivity in the brains of individuals with ASD, this study provides the first direct evidence of synaptic pruning activity deteriorated in human immune cells outside the brain.

Since these findings support the idea that dysfunctions in the elimination of synapse can extend beyond microglia to peripheral immune cells, such as macrophages, Dr. Manabu Makinodan, who is the teacher in the same institution and the author of the corresponding co-color expression of the phagocytes of phagocytes. Future studies can lead to a more effective drug discovery aimed at the central symptoms of the TEA. “

By identifying a measurable deterioration in the macrophage function associated with ASD, this investigation opens a new way to understand the immune synpso interface in autism, which can find potential applications in therapies aimed at restoring the appropriate phagocytic function, which could be a promising future direction.