Abstract
Spinocerebellar ataxia (SCA) is a progressive neurodegenerative disease that affects the cerebellum and spinal cord. Among the 40 types of SCA, SCA type 3 (SCA3), also referred to as Machado-Joseph disease, is the most common. In the present study, we investigated the therapeutic effects of intracranial transplantation of human olfactory ensheathing cells (hOECs) in the ATXN3-84Q mouse model of SCA3. Motor function begins to decline in ATXN3-84Q transgenic mice at approximately 13 weeks of age. ATXN3-84Q mice that received intracranial hOEC transplantation into the dorsal raphe nucleus of the brain exhibited significant improvements in motor function, as measured by the rotarod performance test and footprint pattern analysis. In addition, intracranial hOEC transplantation alleviated cerebellar inflammation, prohibited Purkinje cells from dying, and enhanced the neuroplasticity of cerebellar Purkinje cells. The protein levels of tryptophan hydroxylase 2, the rate-limiting enzyme for serotonin synthesis in the cerebellum, and ryanodine receptor (RYR) increased in mice that received intracranial hOEC transplantation. Because both serotonin and RYR can enhance Purkinje cell maturation, these effects may account for the therapeutic benefits mediated by intracranial hOEC transplantation in SCA3 mice. These results indicate that intracranial hOEC transplantation has potential value as a novel strategy for treating SCA3.