Jobelyn ® improves motor dysfunctions induced by haloperidol in mice via neuroprotective mechanisms relating to modulation of cAMP response-element binding protein and mitogen-activated protein kinase

This study was therefore designed to evaluate the effect of Jobelyn ® (JB), an antioxidant supplement, on haloperidol-induced motor dysfunctions and underlying molecular mechanisms in male Swiss mice. The animals were distributed into 5 groups (n = 8), and treated orally with distilled water (control), haloperidol (1 mg/kg) alone or in combination with each do se of JB (10, 20 and 40 mg/kg), daily for 14 days. Thereafter, changes in motor functions were evaluated on day 14. Brain biomarkers of oxidative stress, proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), cAMP response-element binding protein (CREB), mitogen-activated protei n kinase (MAPK) and histomorphological changes were also investigated. Haloperidol induces postural instability, catalepsy and impaired locomotor activity, which were ameliorated by JB. Jobelyn® attenuated haloperidol-induced elevated brain levels of MDA, nitrite, proinflammatory cytokines and also boosted neuronal antioxidant profiles (GSH and catalase) of mice. It also restored the deregulated brain activities of CREB and MAPK, and reduced the histomorphological distortions as well as loss of viable neuronal cells in the striatum and prefrontal cortex of haloperidol-treated mice. These find ings suggest possible benefits of JB as adjunctive remedy in mitigating parkinsonian-like adverse effects of haloperidol through modulation of CREB/MAPK activities and oxidative/inflammatory pathways.
Source: Metabolic Brain Disease - Category: Neurology Source Type: research