The role of the cerebellum in absence seizures

Date:
May 4, 2022
Source:
Ruhr-University Bochum
Summary:
Researchers have gained new insights into the cellular and molecular
mechanisms of absence seizures and potential therapy options.



FULL STORY ========================================================================== Stimulation of certain cerebellar areas could help combat absence
seizures.

However, what happens at the cellular and molecular level in the brain in
this form of epilepsy and how exactly stimulation has an effect is not
yet understood in detail. Researchers at Ruhr-Universita"t Bochum (RUB)
have gained new insights by conducting experiments with mice. The team
led by Dr. Jan Claudius Schwitalla and Professor Melanie Mark from the
RUB Behavioral Neuroscience research group describes the results in the
journal "Cellular and Molecular Life Sciences" from 19 March 2022. They cooperated with the Erasmus Medical Center in Rotterdam and Utrecht as
well as with colleagues from Bonn, Mu"nster and Mu"nchen.


========================================================================== Abrupt loss of consciousness More than 1.5 million people worldwide
suffer from absence seizures, also known as petit mal seizures. Patients experience an abrupt loss of consciousness and lapse into a paralysis
of behaviour that lasts for a few seconds. Absence seizures often
occur in children between the ages of four and twelve and are often
mistaken for daydreaming. They are linked to altered brain activity,
which is visible in brain activity recordings as so-called spike-and-wave discharges (SWDs). The characteristic activity pattern originates from
the rhythmic and synchronized activity of nerve cells in the cerebral
cortex and thalamus.

Since the nuclei located deep in the cerebellum have a widespread
connectivity to various regions of the brain, researchers proposed that
it might be possible to treat seizures by stimulating the cerebellar
nuclei. Experiments with rodents by other research groups showed that
such stimulation can indeed stop absence seizures. However, it is unclear
what underlies this effect at the cellular and molecular level.

Cerebellar stimulation against abnormal brain activity The Bochum-based researchers worked with mice that develop absence seizures due to a lack
of the P/Q-type calcium channel in nerve cells of the cerebellum.

They found that cells of the cerebellar nuclei were firing abnormally,
and that stimulation of these cells could prevent further SWDs. Therefore,
they stimulated the cerebellar nuclei by administering a pharmacological substance or via chemogenetic stimulation. For chemogenetic stimulation,
a genetically modified receptor is introduced into cells so that they can
be activated by a specifically designed molecule normally not present in
the brain. This allowed the researchers to slowly increase the activity
of the cerebellar nuclei cells and thus prevent the occurrence of further
SWDs in mice.

Furthermore, the team used optogenetic stimulation to briefly increase the activity of cells in the cerebellar nuclei and to stop on-going SWDs after
they have started. This technique uses proteins from algae that can be
turned on by light to increase the activity of nerve cells. Overall, the
study confirmed that targeted stimulation of the cerebellar nuclei could
become a therapeutic approach for people suffering from absence seizures.


========================================================================== Story Source: Materials provided by Ruhr-University_Bochum. Original
written by Julia Weiler.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jan Claudius Schwitalla, Johanna Pakusch, Brix Mu"cher, Alexander
Bru"ckner, Dominic Alexej Depke, Thomas Fenzl, Chris I. De Zeeuw,
Lieke Kros, Freek E. Hoebeek, Melanie D. Mark. Controlling absence
seizures from the cerebellar nuclei via activation of the Gq
signaling pathway.

Cellular and Molecular Life Sciences, 2022; 79 (4) DOI:
10.1007/s00018- 022-04221-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/05/220504110440.htm

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