Epileptic seizures are caused by sudden bursts of excess electrical activity in the brain, leading to a temporary breakdown in normal communication between brain cells. Although it was originally believed that neurones were solely responsible for signalling in the nervous system, it has become increasingly clear that non-neuronal cells called glia – which provide structural and nutritional support for neurones – are also able to modulate neurotransmission. Star-shaped glia known as astrocytes have increasingly been recognised to play a key role in the excessive neuronal synchrony that occurs in epilepsy and researchers at Tufts University and the Children’s Hospital of Philadelphia have now added strong evidence to the case against astrocytes.
The team focussed on reactive astrocytosis, a condition which occurs prominently in response to CNS injury or disease and which has, so far, been difficult to study. Using a virus to selectively cause reactive astrocytosis in mice without triggering broader inflammation and brain injury, the researchers were able to study how the altered astrocytes affected specific synapses in neurones in brain slices from the animals. Normally, neurotransmission is a delicate balance between excitation and inhibition, with the astrocytic enzyme, glutamine synthetase, playing a key role in regulating this balance. In reactive astrocytosis, the astrocytes produce less glutamine synthetase which, in turn, decreases inhibition and leads to the uncontrolled signalling characteristic of epileptic seizures. By adding glutamine – which is depleted as a result of reduced glutamine synthetase activity – the researchers were able to dampen neuronal excitability in the brain slices. The team are continuing to investigate how their research may contribute to developing new treatments for epilepsy and other neurological disorders as well as stroke and traumatic brain injury.
The study is published in the journal Nature Neuroscience.