06 May 2013

Cell transplantation has made up for the lack of brakes in the brain

Stem cells cured epilepsy

Nadezhda Markina, <url>Scientists managed to rid the body of epileptic seizures by implanting inhibitory neurons into it.

The neurons realized what was required of them and extinguished hyperexcitation in the hippocampus. The experiment was successful on mice, but its purpose is the treatment of epilepsy in humans.

Stem cells are opening up new prospects for clinical use. Scientists from the University of California were able to use them to cope with epilepsy, which is poorly amenable to drug therapy. The method was tested on a mouse model of epilepsy. Implantation of neuronal stem cells into the hippocampus almost completely relieved mice from epileptic seizures and improved their behavior. The authors published the results of the experiment in the journal Nature Neuroscience (Hunt et al., GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior).

Epilepsy is a neurological disease characterized by sudden seizures. When a person is convulsing, at the same time he often loses control of the situation, as consciousness turns off, and when falling can get serious damage. Seizures are caused by abnormal activity of many nerve cells in the brain, which are simultaneously excited in the area of the epileptic focus.

Hyperexcited neurons need to be slowed down. In standard treatment, medicinal substances containing gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, are used. But medications must be taken constantly, which is accompanied by side effects – they have a depressing effect on the psyche.

An alternative way is to make some neurons inhibited by other neurons. This role is performed by intermediate cells – interneurons, which are embedded in a hyperexcited neural circuit and extinguish the excitation. All these events develop in the hippocampus, it is there, presumably, that the focus of convulsive activity is located in one of the most severe forms of the disease – temporal lobe epilepsy.

There are not enough inhibitory (inhibitory) interneurons in the hippocampus of epileptics. This may be the cause of pathology. So, the scientists decided, they should be added there.

A group led by Scott Baraban, professor of neurosurgery at the University of California, San Francisco, worked on a mouse model of epilepsy. In order to achieve convulsive seizures and concomitant behavioral disorders in mice, the substance pilocarpine was injected into the hippocampus. As a result, the neurons "broke off the brakes" and generated frequent electrical discharges, and the mice periodically convulsed. The behavior of epileptic rodents changed: they became restless, anxious and aggressive and coped with learning tasks worse than ordinary mice. To strengthen the protection of the brain of mice from hyperexcitation, scientists implanted neuronal stem cells taken from mouse embryos into their hippocampus.

More precisely, these were cells from the so-called medial ganglion tubercle of the mouse embryo brain. It is in this tubercle that neurons are born, which then become inhibitory GABA neurons. In response to the signal coming to them, they secrete the inhibitory neurotransmitter GABA and inhibit the next neuron in the chain. The researchers injected embryonic cells into the hippocampus of adult mice – this is fundamental, since they were looking for a method of treating epilepsy in adults.

The behavior of injected cells in the brain was evaluated on surviving sections of the hippocampus (in which cells remain alive and function). The scientists were convinced that the cells migrated, grew outgrowths and integrated into neural circuits as interneurons. According to their electrical activity, it was clear that the cells began to "work" as inhibitory interneurons. And the transplantation worked on mice in such a way that it almost completely relieved them of epileptic seizures.

In half of the mice, seizures disappeared completely, and in the second half their frequency radically decreased. The behavior of mice treated with cells also changed. The increased anxiety and aggressiveness disappeared, and they became much better at solving spatial learning tasks in a water maze than a group of untreated epileptic mice.

"Our results show that it is possible to use inhibitory neurons for cell transplantation in adults suffering from severe forms of epilepsy," says Baraban. "This technique gives control over seizures and compensates for cognitive deficits in patients."

Scientists at the University of California have taken another step in this direction. In the journal Cell Stem Cell, they report that they have found a way to obtain and cultivate human progenitor cells of GABA neurons (Nicholas et al., Functional Maturation of hpSC-Derived Forebrain Interneurons Requires an Extended Timeline and Mimics Human Neural Development). These cells had to be tested again on mice, but the test showed that in the mouse brain the cells began to work with inhibitory interneurons. This means that they will play the same role in the human brain, experts say.

Portal "Eternal youth" http://vechnayamolodost.ru06.05.2013

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