New neuron injections reduce epileptic seizures

The majority of people visualize the nervous system as a center of activity. Feelings set off nerves, which in turn activate the nerves they are connected to, resulting in a reaction. Frequently disregarded is the reality that calming nerves is equally crucial. A circuit that eventually aids in shutting down muscle activity fails in Parkinson's disease, whereas entire classes of nerves exist only to tell their neighbors to calm down.

Another condition where abnormal nerve activation results in seizures is epilepsy, which is brought on by excessive nerve activity. By grafting more inhibitory neurons, which are derived from embryonic cells, to particular brain regions of epileptic mice, researchers hope to reverse this effect. The strategy proved effective, indicating their the next step is most likely to try doing the same thing with neurons that are stem cell-derived.

Despite the complexity of epilepsy in humans, it is feasible to simulate it in mice by activating acetylcholine receptors with a medication called pilocarpine. When taken properly, pilocarpine is a useful medication. However, when administered systemically (by injection, for instance), the medication enters the brain and results in hyperactivity of the neurons. This may lead to long-term alterations in the structure of numerous neurons in the brain, resulting in a range of symptoms such as seizures, hyperactivity, and changes in spatial memory.

The researchers gave pilocarpine injections to mice to test their epilepsy treatment, and then they kept a close eye on the animals for several days. For the study, only those who had seizures were used.

There are several types of inhibitory neurons known to exist, however the Since interneurons are nerve cells that form connections with other nerve cells and GABA is an inhibitory neurotransmitter, the authors were particularly interested in the brain's GABA-producing interneurons. These are produced in a particular region of the early brain approximately two weeks into a mouse's embryonic development. Simply said, the researchers removed that region of the developing brain to obtain a source of these GABA cells before they reached adulthood. The mice were genetically tagged with a gene that produces a fluorescent protein in order to ensure that they could locate these cells in the adult animals.

Going back to the epileptic mice, the researchers divided the animals into three groups: untreated mice, mice that had immature neurons injected into the hippocampus, a relevant region of the brain, and mice that had the cells injected into the amygdala, a non-relevant region of the brain.

The green-glow cells, which indicated that they were transplanted, matured and assimilated into the adult brain sixty days later. Some had not only clustered at the injection site but had spread throughout the brain before maturing, moving away from the site of injection.

For the most part, the process worked well. When compared to either of the control groups, the animals who received the appropriate injections experienced a reduction in seizures of over 90%. During the week that they were under observation, half of the mice did not have any seizures. The treatment also prevented the mice from exhibiting other symptoms, such as decreased aggression, reduced hyperactivity, and improved spatial memory.

However, this should not be interpreted as stopping the pilocarpine course of treatment. There were still the anatomical alterations in the brain brought on by the medication. Not all of the symptoms were alleviated by the hippocampal creation of new inhibitory cells; the mice continued to exhibit anxiety and seemed hyperactive in stressful situations. Furthermore, the amygdala proved to be the incorrect site for the immature neurons to be injected, which for some reason effectively inhibited hyperactive behavior.

The extra inhibitory neurons prevented the pharmacological treatment from causing epilepsy, as opposed to negating its effects. Considering that there are numerous causes of epilepsy in humans, this may be more beneficial.

However, it's crucial to stress that—while valuable—this work is only a first step toward a treatment. The logical next step would be to use stem cells to create the immature neurons. That would entail coercing the cells into taking on the characteristics of neural cells and then reprogramming them to become GABA inhibitory neurons' native identity. To ensure that the effect is widespread, the procedure should then likely be tested on other models of epilepsy. It will be necessary to have all of these validations before attempting this procedure on humans.