Neuroprotective potential of Cilostazol in 3-NP provoked Huntington's disease-associated symptoms

Abstract

Huntington's disease (HD), a neurodegenerative condition specified by mitochondrial deficits, psychiatric and cognitive impairment developed due to neuronal damage in the brain. 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase develops behavioral, biochemical as well as histological alterations in the striatal region of brain, which resembles HD in humans. Phosphodiesterases (PDEs) participate in cognition, motor functions, and behavior as well as also offers neuroprotection. The present investigation was framed to analyze the neuro-defensive characteristics of cilostazol PDE3 inhibitor over the 3-NP induced behavioral, striatal and mitochondrial deficits. Administration of 3-NP (10mg kg-1; i.p.) for the duration of 14 days has shown considerable alterations in behavior such as decreased locomotion (actophotometer), reduced grip strength (rota-rod test), spatial learning memory (elevated plus maze and Morris water maze). In parallel to, 3-NP treated rats exhibit biochemical changes such as increased oxidative stress (enhanced lipid peroxides, reduced glutathione, catalase, and superoxide dismutase), disturbed cholinergic function (increased acetylcholinesterase activity), increased inflammation (more myeloperoxidase) and mitochondrial dysfunction (reduced complex I, II and IV activity). Histopathological changes (Nissl stain) like chronic neuronal gap, pyknotic nuclei as well as injured cells in the cerebral cortex and hippocampus were also observed in 3-NP treated rats. Administration of cilostazol considerably restored behavioral abnormalities, biochemical and histopathological alterations. In this investigation, cilostazol offered neurodefensive effects which were established by behavioral and biochemical paradigms, which confirmed the potent neurodefensive aspect of cilostazol in 3-NP provoked behavioral and biochemical abnormalities.