Experience of experimental simulation of Huntington’s disease

Abstract

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease characterized by choreic hyperkinesia, cognitive decline, behavioral disorders, and progressive neuronal death affecting primarily the striatum. The fatal nature of HD makes searching for new effective methods of treatment topical, which requires the development of experimental models of the disease. This model can be created on the basis of 3-nitropropionic acid (3-NPA) that is a neurotoxin causing characteristic changes in motor skills and memory impairment in animals due to induction of oxidative stress, impaired glutathione defense, and destruction of striatal cells. HD in rats was simulated by chronic intraperitoneal administration of 3-NPA daily for 17 days. Systemic administration of a low dose of 3-NPA (10 mg/ kg) induced hyperactivity of the animals in the open field test (including movement redundancy as a hyperkinesia analogue) and had no effect on the behavior of the animals in the X-maze test. On the contrary, rats administered with a toxic dose of 3-NPA (20 mg/kg) demonstrated a significant decrease in the motor activity an cognitive decline in behavioral tests. Histopathological analysis revealed damage and loss of neurons and decreased expression of dopaminergic markers (tyrosine hydroxylases and plasma membrane dopamine transporter) in the striatum. Also, a gliotoxic effect of 3-NPA in the striatum was found, which was confirmed by immunohistochemical staining for astrocytic proteins: GFAP, glutamine synthetase, and aquaporin-4. This HD model may be helpful for testing new experimental therapies at various stages of neurodegeneration of the Huntington type, including those based on cell neurotransplantation.