Cell communication after epileptic seizures regulates brain’s immune response
Microglia are a group of cells that act as the first and main form of immune defence in the central nervous system. They make up between 10 and 15% of the brain's total number of cells and play an important role in returning the brain to health after trauma or disease. Scientists have not yet fully understood the way these cells are regulated to produce the appropriate immune response.
However, researchers led by Dr Long-Jun Wu from Rutgers University have now shown a mechanism by which neurons control changes in the movement and growth of microglia after a seizure. These findings may inform future research on therapeutic strategies for disorders such as epilepsy, leading to better treatments.
Seizures are associated with an increase in the release of glutamate, an excitatory neurotransmitter, by neurons. This causes a spike in neuronal activity and leads to an increase in the growth of microglial processes towards the neurons. Thus, suggesting microglia have a neuro-protective function following these periods of hyperactivity.
Excitatory neurotransmitters are chemicals released at a synapse that makes the neuron on the other side of that synapse – the postsynaptic neuron – more likely to propagate an electrical signal.
Further investigations showed that through a series of molecular signals, the postsynaptic neuron releases ATP, another neurotransmitter, creating a concentration gradient towards itself. The microglia can sense this gradient using a specific ATP receptor known as the P2Y12 receptor.
To test their research they genetically engineered mice that did not express this receptor on their microglia. They found that these mice were unable to respond with extensions in their microglial processes after seizures and they also showed worse levels of seizure activity.
Two-photon imaging of microglial process motility/growth before and after glutamate application
Two-photon imaging of migrating microglial processes - Dr Eyo at Dr Wu's Lab - Rutgers University
Hopefully, future studies will be able to show how the neuro-protective function of microglia operates after a seizure.
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