MSGID: 1:317/3 62735354   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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   
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   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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