Researchers use AI to rescue embryos from brain defects by re-engineering cellular voltage patterns.
Improper neural patterning during brain development leads to serious disorders such as open neural tube defects, brain malformations, and susceptibility to autism and degenerative disorders like Parkinson’s and Alzheimer’s diseases. There are currently no clinically approved interventions for brain patterning disorders. therefore, finding regenerative and repair strategies for brain patterning is a critical unmet need in medicine. Now, a study from researchers at Tufts University shows electrical patterns in the developing embryo can be predicted, mapped, and manipulated to prevent defects caused by harmful substances such as nicotine. The team state their research suggests that targeting bioelectric states may be a new treatment modality for regenerative repair in brain development and disease, and that artificial intelligence (AI) can be used to find effective repair strategies. The opensource study is published in the journal Nature Communications.
Previous studies show that in a developing embryo groups of cells create patterns of membrane voltage which precede and control the expression of genes, and the morphological changes occurring over the course of development. The global medical community are now beginning to see how electrical patterns in the embryo are guiding large-scale patterns of tissues, organs, and limbs. It is highly desirable to decode this electrical communication between cells to use it to normalize development or support regeneration in the treatment of disease or injury. The current study uses deep-learning to predict the bioelectrical patterns which occur in normal and nicotine-exposed embryos, to identify reagents that might restore the normal patterning.
The current study develops a powerful computational simulation platform, called the BioElectric Tissue Simulation Engine (BETSE), to create a dynamic map of voltage signatures in the developing brain of a frog embryo. Results show that the BETSE model accurately replicates the distinct pattern of membrane voltage from the normal embryonic brain development, and also explains the erased electrical pattern observed due to nicotine exposure.
The group also used BETSE to explore the effect of various reagents on the embryo’s voltage map. Data findings show that one reagent, the hyperpolarization-activated cyclic nucleotide gated channel (HCN2), when added to the cells in the model selectively enhanced a large internal negative charge, or hyperpolarization, in areas of the brain diminished by nicotine. Results show that expressing HCN2 in live embryos rescues them from the effects of nicotine, restores a normal bio-electric pattern, brain morphology, markers of gene expression, and near normal learning capacity in the grown tadpole.
The team surmise that they successfully used AI to map the biophysical mechanism of developmental brain damage, and correctly predict that HCN2 ion channels will restore the bioelectric prepatterns necessary for brain patterning after nicotine exposure. For the future, the researchers state activation or expression of specific channel is a general strategy for biomedical approaches to complex organ patterning in the context of birth defects, regenerative medicine, and bioengineering.
Source: Tufts University