Protective effect of INI-0602, a gap junction inhibitor, on dopaminergic neurodegeneration of mice with unilateral 6-hydroxydopamine injection

INI-0602, a novel gap junction hemichannel inhibitor, was administered to hemi-Parkinsonism mice generated by striatal 6-hydroxydopamine injection. INI-0602 prevented the toxic activation of microglia, such as the increased number of the activated form, enlargement of cell bodies and induction of proinflammatory cytokines, such as IL-1 beta and TNF alpha, in the ipsilateral striatum. On the other hand, INI-0602 induced the expression of neurotrophic factors, such as brain-derived neurotrophic factor and NT-4/5, in the 6-hydroxydopamine-treated striatum. INI-0602 treatment blocked not only dopaminergic loss in both the striatum and substantia nigra, but also apomorphine-induced rotational behavior.