A Preexisting Toxoplasma Gondii Infection Exacerbates Epileptogenesis in a Self-sustained Electrical Status Epilepticus Mouse Model of Temporal Lobe Epilepsy
Abstract number :
1.476
Submission category :
1. Basic Mechanisms / 1A. Epileptogenesis of acquired epilepsies
Year :
2023
Submission ID :
1278
Source :
www.aesnet.org
Presentation date :
12/2/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Sandy Shultz, PhD – Monash University
Tamara Baker, PhD – Monash University; David Wright, PhD – Monash University; Idrish Ali, PhD – Monash University; Nigel Jones, PhD – Monash University; Mujun Sun, PhD – Monash University; Peravina Thergarajan, PhD – Monash University
Rationale: The neurotropic parasite Toxoplasma gondii incurably infects one-third globally. Being mainly transmitted through contaminated food and water, the parasite is able to disseminate beyond the gut, hijack immune cells, breach the blood-brain barrier, and manipulate the neuroinflammatory environment. Neuroinflammation plays a pivotal role in epileptogenesis and preliminary evidence suggests T. gondii is a risk factor for epilepsy; however, how a T. gondii infection influences the epileptogenic process is unknown. Therefore, this study aimed to elucidate whether a pre-existing T. gondii infection alters the neuroinflammatory environment and facilitates epileptogenesis in a self-sustained electrical status epilepticus (SSSE) mouse model of mesial temporal lobe epilepsy.
Methods: Six-week-old male and female C57BL/6 Jax mice were intraperitoneally administered either T. gondii tachyzoites or PBS. At four weeks post-injection (i.e., once a chronic T. gondii infection was established), mice underwent electrode implantation, with a bipolar stimulating electrode placed into the right ventral hippocampus. At six weeks post-injection, mice underwent a 90-minute electrical stimulation through the bipolar electrode to induce status epilepticus (SSSE) or were assigned to the control group. Video-EEG recordings were taken between 0-4 weeks and 12-16 weeks post-stimulation. Gene expression was assessed within one week of SSSE and neuropathology was evaluated at 16-weeks post-SSSE via ex vivo MRI and immunohistochemistry.
Results: Both male and female T. gondii mice had increased spontaneous seizures at 16-weeks post-SSSE compared to their uninfected counterparts. Post-mortem analysis found an exacerbated neuroimmune response and oxidative stress within one week post-SSSE in the infected mice, and MRI analysis at 16-weeks found sex specific changes in temporal lobe structures of the T. gondii mice with epilepsy.
Conclusions: These findings support the notion that a pre-existing T. gondii infection alters the neuroinflammatory environment and epileptogenesis in a mouse SSSE model of mesial temporal lobe epilepsy in both sexes. Considering the widespread prevalence of this infection it may have important implications for humans with epilepsy.
Funding: Brain Foundation Australia
Basic Mechanisms