Experience of experimental simulation of Huntington’s disease

Abstract

Huntingtons disease (HD) is an autosomal dominant neurodegenerativedisease characterized by choreic hyperkinesia, cognitivedecline, behavioral disorders, and progressive neuronaldeath affecting primarily the striatum. The fatal nature of HDmakes searching for new effective methods of treatment topical,which requires the development of experimental models of thedisease. This model can be created on the basis of 3-nitropropionicacid (3-NPA) that is a neurotoxin causing characteristicchanges in motor skills and memory impairment in animals dueto induction of oxidative stress, impaired glutathione defense,and destruction of striatal cells. HD in rats was simulated bychronic intraperitoneal administration of 3-NPA daily for 17days. Systemic administration of a low dose of 3-NPA (10 mg/kg) induced hyperactivity of the animals in the open field test (includingmovement redundancy as a hyperkinesia analogue) andhad 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 activityan cognitive decline in behavioral tests. Histopathologicalanalysis revealed damage and loss of neurons and decreasedexpression of dopaminergic markers (tyrosine hydroxylases andplasma membrane dopamine transporter) in the striatum. Also,a gliotoxic effect of 3-NPA in the striatum was found, which wasconfirmed by immunohistochemical staining for astrocytic proteins:GFAP, glutamine synthetase, and aquaporin-4. This HDmodel may be helpful for testing new experimental therapies atvarious stages of neurodegeneration of the Huntington type, includingthose based on cell neurotransplantation.

Keywords

• huntington disease
• 3-nitropropionic acid
• experimental simulation
• behavioral and memory disorders
• striatum
• neuronal death
• gliotoxicity