Rodent models of genetic epilepsy and its association with neurocognitive impairment- a systematic review

TL;DR

This review examines how genetic epilepsy in rodent models affects cognitive and behavioral functions, revealing impairments that vary with mutations and developmental stages.

Contribution

The study systematically reviews cognitive and behavioral outcomes in rodent models of genetic epilepsy, highlighting gene-driven and seizure-driven mechanisms.

Findings

Rodent models of genetic epilepsy show impaired memory, learning, and behavioral abnormalities like ASD-like traits, anxiety, and depression.

The severity and domains of cognitive and behavioral impairments vary across mutations, strains, and developmental stages.

The findings suggest both seizure-driven and gene-driven mechanisms contribute to cognitive deficits in genetic epilepsy.

Abstract

Epilepsy is a neurological disorder affecting almost 50 million people worldwide, with genetic epilepsy (GE) representing a subset caused by specific gene mutations. While cognitive deficits are frequently reported in epilepsy, the contribution of GE itself remains poorly defined. We conducted a systematic review to evaluate the cognitive and behavioral phenotypes in rodent models of GE, focusing on cognition as the primary outcome and behavior as secondary. Literature searches of PubMed, Ovid MEDLINE, and Scopus identified 16 eligible studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Across models, rodents with GE commonly exhibited impairments in the neurocognitive and behavioral paradigms. Mutant rodent models were exhibit poorer memory and learning abilities, alongside behavioral abnormalities such as autism spectrum disorder (ASD)-like phenotype, anxiety, and depression. However, the severity and domains of impairment varied across mutations, strains, and developmental stages, reflecting the heterogeneity of GE. Our findings highlight both seizure-driven and gene-driven mechanisms of cognitive impairment and underscore the need for syndrome-specific investigations. Overall, rodent models provide valuable insights into the cognitive comorbidities of GE, but future research requires improved methodological rigor and broader use of complementary models to clarify underlying mechanisms and guide targeted interventions.

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