Interactions of Antibodies to the Gram-Negative Gastric BacteriumHelicobacter pyloriwith the Synaptic Calcium Sensor Synaptotagmin 5, Correlate to Impaired Vesicle Recycling in SiMa Human Neuroblastoma Cells

Due to molecular mimicry, maternal antibacterial antibodies are suspected to promote neurodevelopmental changes in the offspring that finally can cause disorders like autism and schizophrenia. Using a human first trimester prenatal brain multiprotein array (MPA), we demonstrate here that antibodies to the digestive tract bacteriaHelicobacter pylori(alpha-HPy) andCampylobacter jejuni(alpha-CJe) interact with different synaptic proteins, including the calcium sensor synaptotagmin 5 (Syt5). Interactions of both antisera with Syt5 were confirmed by Western blot with a HEK293-cells overexpression lysate of this protein. Immunofluorescence and Western blotting revealed SiMa cells to express Syt5, which also co-migrated with a band/spot labeled by either alpha-HPyor alpha-CJe. Functionally, a 12-h pretreatment of SiMa cells with 10 mu g/ml of either alpha-HPyor alpha-CJeresulted in a significant reduction of acetylcholine(ACh)-dependent calcium signals as compared to controls. Also ACh-dependent vesicle recycling was significantly reduced in cells pretreated with either alpha-HPyor alpha-CJe. Similar effects were observed upon pretreatment of SiMa cells with Syt5-specific antibodies. In conclusion, the present study supports the view that prenatal maternal antibacterial immune responses towardsHPyand by this to Syt5 are able to cause functional changes, which in the end might contribute also to neurodevelopmental disorders.

Automated summary

Maternal antibacterial antibodies may impact fetal neurodevelopment, potentially leading to disorders like autism and schizophrenia. Experimental evidence shows interaction between maternal antibodies and gut bacteria, altering the function of synaptic proteins.