Behavioral Paradigms in Rodent Models of Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) remains an untreatable neurodegenerative disease without a cure or effective treatment, mainly due to elusive underlying mechanisms. ALS is primarily characterized by motor neuron dysfunction in the brain and spinal cord. However, it also exhibits non-motor symptoms such as executive, behavioral, and language dysfunction, making it challenging to establish informative disease models for relevant preclinic and clinical research. The discovery of ALS- causing genes, such as C9orf72 and SOD1, has paved the way for developing various animal models. Among these models, rodents have emerged as particularly valuable, demonstrating unique ALS-related behavioral defects in multiple behavioral tests. These models enable further understanding of disease mechanisms and provide sensitive and precise functional assessments of ALS-related defects for drug development. This report endeavors to present a chronological overview of various behavioral assessments, encompassing motion ability tests, cognitive evaluations, sensory analyses, and other paradigms described in rodent models of ALS. Our goal is to summarize and compare the behavioral alterations observed in diverse rodent models of ALS with distinct gene mutations, thus providing comprehensive references and guidance for advancing pathogenic and therapeutic research in ALS.