Objective: We investigated whether intrastriatal injection of ionomycin to hemiParkinsonian rats produced changes in L-DOPA responses including LID and analyzed the effects of ionomycin on key molecular mediators of LID.

Background: Dephosphorylation of dopamine and c-AMP regulated phosphoprotein of 32 kDa (DARPP-32) by activated calcineurin may help reduce L-DOPA-induced dyskinesia (LID). One important activator is ionomycin.

Methods: Rats were subjected to 6-OHDA lesion in the medial forebrain bundle (MFB). The successful hemiParkinsonian rats were treated with L-DOPA to induce LID, of which some rats were intrastriatally injected with ionomycin. Stepping test, abnormal involuntary movements scoring (AIMs), western blotting and immunochemistry were used to evaluate the effect of iononmycin.

Results: Ionomycin can downregulate the phosphorylation of DARPP32 at Thr-34 and reduce LID. Furthermore, ionomycin decreased two established molecular markers of LID, fosB/ΔFosB and phosphorylated ERK1/2. Ionomycin also decreased the phosphorylation of three main subunits of the NMDA receptor, NR1 phosphorylated at ser896, NR2A phosphorylated at Tyr-1325, and NR2B phosphorylated at Tyr-1472. However, striatally injected ionomycin also reduced the antiParkinsonian action of L-DOPA.

Conclusions: These data indicate that ionomycin largely interacts with striatal mechanisms that are critical to the L-DOPA motor response highlighting the role of protein dephosphorylation by calcineurin.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/intrastriatal-injection-of-ionomycin-profoundly-changes-motor-response-to-l-dopa-and-its-underlying-molecular-mechanisms/