The gut microbiota and derived metabolites impact neuroinflammation and neuronal excitation, modulating seizure development in a mouse model of viral-induced epilepsy
Presentation Time: 03:00 PM - 03:15 PM
Abstract ID: 6076 - B
Presenting Author:
Ana Beatriz DePaula-Silva , Assistant Professor at Univ. of Utah
Abstract:
Temporal lobe epilepsy is a prevalent form of acquired epilepsy. Inflammation alters neuronal excitatory/inhibitory balance and is a significant cause of seizures. Despite gut microbiota’s role in modulating inflammation in various disorders, its influence on neuroinflammation and acquired seizure/epilepsy remains unclear.
Mice intra-cranially (IC) infected with Theiler’s murine encephalomyelitis virus (TMEV) develop behavioral seizures 3-8 days post-infection (dpi). Seizures are correlated with innate immune response activation and macrophage infiltration into the CNS. The ketogenic diet, an epilepsy treatment, modulates gut composition. We hypothesized that the presence of specific gut bacterial population(s) and derived metabolites modulate neuroinflammation and seizures.
Mice on the 2920X or the 8904 Teklad Rodent-diet were TMEV-infected. Seizures were determined daily (3-7dpi). At 7dpi, mice were euthanized, brain cells isolated, and their inflammatory states determined by flow cytometry. Fecal samples were collected on days -1 and 7dpi. 16S rRNAseq was performed in fecal samples. Metabolomics was conducted on plasma/fecal samples.
The 8904-diet showed increased seizure incidence and severity, elevated CNS macrophage infiltration, and reactive microglia. Significant changes in microbiota diversity and distinct metabolite profiles were observed.
Therefore, manipulating the gut microbiota/derived metabolites may offer promising interventions to prevent/ treat epilepsy.
The gut microbiota and derived metabolites impact neuroinflammation and neuronal excitation, modulating seizure development in a mouse model of viral-induced epilepsy
Category
Poster and Podium (Block Symposium)