Nootropic Effects of Mitoq, a Mitochondria-targeted Antioxidant, in a Mouse Model of TLE
Abstract number :
1.133
Submission category :
2. Translational Research / 2D. Models
Year :
2022
Submission ID :
2204322
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Authors :
Segewkal Hawaze Heruye, B Pharm, MS – Creighton University; Stephanie Matthews, BS, MS. – Lab Manager, Pharmacology and Neuroscience, Creighton University; Kristina Simeone, PhD – Associate Professor, Pharmacology and Neuroscience, Creighton University; Peter West, PhD – Research Assistant Professor, Pharmacology and Toxicology, University of Utah; Timothy Simeone, PhD – Associate Professor, Pharmacology and Neuroscience, Creighton University
This abstract has been invited to present during the Translational Research platform session
Rationale: Temporal lobe epilepsy (TLE) is often comorbid with substantial cognitive impairment. Oxidative stress and reduced mitochondrial respiratory chain complex I (MRCI) function has been found in human TLE resected brain tissue. Similarly, the Kv1.1 knockout (KO) mice, a preclinical model of TLE, displays cognitive deficits and reduced hippocampal long-term potentiation. KO hippocampal mitochondria also have reduced MRCI function which is due to inhibition by reactive oxygen species (ROS). Thus, we hypothesize that excessive mitochondrial ROS contributes to impaired hippocampal-mediated memory in KO mice which can be rescued with a mitochondrial targeted antioxidant.
Methods: Sub-chronic in vivo experiments: Mice (WT and KO) were injected intraperitoneally with either 5 mg/kg MitoQ or vehicle daily for five days and habituated to the arena prior to testing. On test day mice were allowed to investigate two similar objects in the training phase. Anxiety was evaluated by measuring thigmotaxis. Novel location recognition (NLR) was assessed after one of the objects was moved to a different location. Novel object recognition (NOR) was tested after one of the objects was replaced with a new object. The exploration times during the tests were quantified and discrimination indices were calculated. Post-behavioral testing, levels of mitochondrial superoxide were assessed in ventral hippocampal sections. Acute ex vivo experiments: Short- and long-term plasticity (STP and LTP) were determined in ventral hippocampal slices from WT and KO mice using planar multielectrode arrays. Schaffer collaterals were stimulated, and postsynaptic extracellular field potentials were recorded in CA1 stratum radiatum. Stimulations were used to elicit paired pulse facilitation and long-term potentiation. After stable baseline recordings were achieved, MitoQ (500 nM) was perfused onto the slices and stimulations were repeated. Levels of mitochondrial superoxide, a prominent ROS, were assessed using MitoSox Red. A two-way ANOVA with Tukey’s post-hoc test was used with p< 0.05 considered significant.
Translational Research