Brain proteins associated with seizures and abnormal social behavior

Riverside has discovered a new mechanism, led by a biomedical scientist at the University of California, involved in the abnormal development of neuronal connections in the mouse brain that lead to seizures and abnormal social behavior.

Researchers focused on what is called a region of the brain Hippocampus, It plays an important role in learning and social interaction. Synapses are special contacts between neurons.

Each neuron in the brain receives numerous excitatory and inhibitory synaptic inputs. Known as E/I balance, essential for circuit function and stability, and thought to be important for central nervous system information processing, the balance of neural circuit excitation and inhibition is associated with many nerves, including: Can play a role in causing disability Epilepsy, Autism spectrum disorder,and schizophrenia..

The researchers also looked at a protein called ephrinB1 that spreads to the membranes that surround cells and maintains the nervous system. The aim of their study was that deletion or overproduction of ephrinB1 in astrocytes, the glial cells of the brain that regulate synaptic connections between neurons, affects synapse formation and maturation in the developing hippocampus, E/I Balances and leads to behavioral disorders.

“We found that changes in E/I balance were regulated by developing brain astrocytes through ephrin proteins.” Irina Etel,Professor Biomedical In UCR Medical school Who led the rat Investigation.. “Furthermore, astrocyte ephrinB1 is linked to the development of inhibitory networks in the hippocampus during key developmental periods, a new and unexpected finding. Specifically, the loss of astrocyte ephrinB1 , Decreasing inhibition promotes excitement and activates neural circuits, suggesting that this hyperactivity appears as a decrease in sociality in mice and may serve as a new model for studying autism spectrum disorders. I am.”

Survey results announced in Journal of Neuroscience, Could further deepen scientists’ understanding of the mechanisms that lead to neurodevelopmental disorders and allow researchers to discover new interventions to treat these disorders by targeting astrocytes during specific developmental periods. I will.

Ethell explains that astrocyte dysfunction is also associated with synaptic pathologies such as neurodevelopmental disorders and neurodegenerative disorders. Alzheimer’s disease Early dysfunction of synaptic connections can also lead to neuronal loss.

“How exactly astrocytes use ephrin proteins to control the development of neural networks has not been explored in future studies,” she said. “Observation disorders open up new horizons for future clinical applications, as impairment disorders are associated with several developmental disorders, including autism and epilepsy.”

This report is first to establish an association between the development of astrocytes and E/I balance in the mouse hippocampus during early postnatal development.

“We provide new evidence that different estrin B1 levels of astrocytes affect both excitatory and inhibitory synapses during development and contribute to the formation of neural networks in the brain and related behaviors,” Ethel said. Said.

She explained that synapses are the building blocks of neural networks, functioning as the basic information processing units of the brain. She said that excitatory synapses are cell-cell junctions that promote neural activity, whereas inhibitory connections negatively regulate brain activity to regulate brain activity, its timing, and specificity. Stated.

“Nervous network hyperactivity resulting from loss of inhibitory synapses or dysfunction can lead to neurological dysfunction and seizures,” she added. “Like a car without brakes, a brain without inhibitory neurons can’t function properly, becomes overactive, and loses control of the body.”

Ethell needs further investigation to determine how astrocyte ephrin signaling alters inhibitory synapses, and specifically how astrocytes contribute to these mechanisms I admitted that.

“Owing to the growing interest in extensive research into astrocyte-mediated mechanisms that regulate the E / I balance of neurodevelopmental disorders, our findings show that astrocytes in clinically relevant conditions Establishing the foundation for future research,” she said.