Kolaviron ameliorates behavioural deficit and injury to striatal dopaminergic terminals via modulation of oxidative burden, DJ-1 depletion and CD45R ⁺ cells infiltration in MPTP-model of Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disease. Currently, the precise pathogenic detail of PD is not entirely clear and first line therapeutics fail to attenuate the progress of the disease. In this study, we examined the neuroprotective effect of kolaviron, a natural antioxidant and anti-inflammatory biflavonoid from Garcinia kola seed, on behavioural impairment, neurodegeneration, oxidative stress and neuroinflammation in an acute MPTP-induced PD model. Kolaviron mitigated the frequently interrupted MPTP-associated hyperkinesia, inefficient gait, immobility, inability to pay attention to sizable holes on walking path, habitual clockwise rotations characterized with minimal diversion of movements and impaired balance. Also, kolaviron suppressed MPTP-mediated striatal oxidative stress, depletion as well as degeneration of dopaminergic terminals, reduced DJ-1 secretion and upregulated expression of caspase-3. Kolaviron facilitated cytoprotective antioxidant response and prevented MPTP-mediated neuroinflammation by blocking striatal infiltration of peripheral CD45R positive cells. Additionally, kolaviron reversed MPTP-induced inhibition of acetylcholinesterase activity. Together, our study provides evidence that the neuroprotective capacity of kolaviron to modulate striatal degeneration, behavioural impairment, antioxidant/redox imbalance and neuroinflammation implicated in the pathogenesis of PD may involve upregulation of DJ-1 secretion and inhibition of CD45R cells infiltration. Our data recommend kolaviron as a possible neuroprotective strategy in the management of Parkinson's disease and the associated behavioural complications, albeit the identity of MPTP-associated striatal CD45R infiltrate needs to be further characterized.

Keywords: Behavioural incompetence; CD45R; DJ-1; Kolaviron; MPTP; Striatum.