Targeting mitochondrial respiratory complex I deficiency and uncoupling function can produce anti-epileptic effect in acute/temporal lobe epilepsy genetic model

Targeting mitochondrial respiratory complex I deficiency and uncoupling function can produce anti-epileptic effect in genetic model of temporal lobe epilepsy and acute temporal lobe epilepsy

Kristina A. Simeone, Stephanie A. Matthews, Kaeli K. Samson, Timothy A. Simeone  
Pharmacology Department, Creighton University School of Medicine, Omaha, NE 68178, USA

Department of Pharmacology, Creighton University School of Medicine, Nebraska 68178, USA

Mitochondria participate in the neurotransmission process by actively providing energy (ATP) and maintain appropriate concentrations of reactive oxygen species (ROS) in presynaptic and postsynaptic spaces. In human and animal epilepsy, respiration caused by mitochondrial respiratory complex (MRC) and production of ATP is reduced, and antioxidant system attenuation and oxidative damage are increased. The researchers report that MRCI- driven respiratory and functional uncoupling (inducible antioxidant effects) is reduced and H 2 O 2 levels are elevated in mitochondria isolated from knockout mice. Experiments were performed to reduce PT -type hippocampal slices by rotenone in the mossy fiber-hippocampal CA3 synaptic region to reduce PPRs (similar to KO PPRs ) and to aggravate in vitro epileptic activity.

Daily AATP [ a mixed chemical – ingredients with ascorbic acid (AA) , alpha-tocopherol , sodium pyruvate (P)) ; designed primarily for synergistic targeting of mitochondrial damage Administration, can improve mitochondrial function, mossy fiber PPRs , and reduce the frequency of epileptic load index (SBI) and epileptic seizures in knockout mice.

AATP pretreatment reduced the severity of KA- induced seizures and resulted in 100% protection in severe tonic-clonic seizures in WT mice. The data suggest that restoring the dynamic balance of bioenergy in the brain is a viable antiepileptic target for temporal lobe epilepsy.

Record spontaneous and evoked potential methods:

Mouse hippocampal slices were removed by conventional methods and perfused. Rotenone (100 nM) or DMSO (0.01%) for perfusion ( 60 minutes), during which the paired stimulation of the portal area was applied every 90 seconds (50 ms interval, intensity is 50% of the highest response). After the stimulation, high concentration of potassium ions (8 mM) aCSF was perfused with rotenone or DMSO for 90 minutes to cause seizure-like events (SLEs) . Signals were recorded and analyzed by the MED64 multichannel extracellular electrode system of Alpha Medical Scientific , Japan.

Med64 planar multi-electrode array recording system

Detailed information: KA Simeone et al. / Experimental Neurology 251 (2014) 84–90

To measure mitochondrial function, researchers can acquire ATP , ROS and Luxcel extracellular oxygen consumption rate OCR and extracellular acidification rate ECA reagent through a multi-function plate reader with high-end time-resolved fluorescence and chemiluminescence functions (eg BMG Labtech Clariostar , Germany). Boxes [if possible, please hyperlink these key words], etc., to facilitate the measurement of various important data of metabolism.

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