Abscisic Acid Enhances Motor and Cognitive Function in the 3-Acetylpyridine Mouse Model of Cerebellar Ataxia

Abstract

Cerebellar ataxia is a debilitating neurodegenerative disorder characterized by impaired motor coordination and balance with limited treatment options. Abscisic acid (ABA), a phytohormone detected in mammalian brains, has shown neuroprotective properties. This study investigated the effects of ABA on motor, cognitive, and affective deficits in a mouse model of cerebellar ataxia in which male Swiss mice received a single intraperitoneal injection of 3-acetylpyridine (3-AP; 60 mg/kg), which leads to the loss of climbing fiber input to Purkinje neurons leading to cerebellar degeneration. In ABA-treated groups, ABA (10 or 15 μg/mouse) was intracerebroventricularly applied for four consecutive days. Behavioral testing consisted of open field, footprint analysis, wire grip, rotarod, tail suspension, elevated plus maze, Morris water maze, and the passive avoidance assay. Cerebellar brain-derived neurotrophic factor (BDNF) levels were measured using ELISA. As expected, 3-AP-treated mice exhibited significant motor impairments, increased anxiety-like and depressive-like behaviors, and cognitive deficits. ABA treatment, particularly at the 15 μg/mouse dose, significantly improved motor coordination, locomotor activity, memory, and spatial and passive avoidance learning as well as reduced anxiety-like and depressive-like behaviors. Behavioral changes were associated with normalization of the 3-AP-induced increases in cerebellar BDNF levels. This study demonstrates that ABA can ameliorate motor, cognitive, and affective deficits in a mouse model of cerebellar ataxia, which could involve BDNF and be due to neuroprotective effects in the cerebellum. By extension, our data suggest that ABA may have therapeutic potential in the management of cerebellar ataxia and other cerebellar disorders.