Objective: Our research sought to unravel the pharmacological effects and mechanisms of action of Rolipram through both in vivo and in vitro experimentation in models simulating Parkinson’s disease.

Background: Rolipram, a targeted inhibitor of phosphodiesterase IV, has demonstrated recent promise in providing neuroprotective benefits in transgenic mouse models.

Method: In our unique methodology, SK-N-LP cells were subjected to the effects of rolipram (25μM) in the presence of 1-methyl-4-phenylpyridinium iodide (MPP+) to mimic an in vitro model of Parkinson’s disease. Apoptotic markers such as B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) and mitochondrial respiratory capacity were measured. 

Moving to the in vivo model, behavioral assessments including quantification of vacuous chewing movements (VCM), tongue protrusions (TP), orofacial bursts (OB), grip strength, and narrow beam walking, as well as locomotor activity analysis, were conducted. Furthermore,  immunohistochemistry was employed to gauge the protective effects of rolipram (at doses of 25 and 50 mg/kg body weight). Molecular markers including tyrosine hydroxylase (TH), cAMP response element-binding protein (CREB), lipid peroxidation, and levels of cytokines such as IL-1β, IL-6, and TNF-α were assessed in rats.

Results: Rats administered with MPP+ exhibited a substantial decrease in locomotor activity and manifested vacuous chewing movements (VCMs), orofacial bursts (OBs), and tongue protrusions (TPs). Treatment with Rolipram mitigated the apoptotic effects induced by MPP+ in both SK-N-LP cells and human dopaminergic neurons. Additionally, Rolipram enhanced mitochondrial respiratory capacity, reduced lipid peroxidation, and restored mitochondrial morphology. In rat subjected to MPTP treatment, Rolipram exhibited a significant improvement in motor functions in a dose-dependent manner. Notably, Rolipram prevented the loss of dopaminergic neurons, reduced phosphorylated CREB, and suppressed glial activation of MPTP-treated rat. Furthermore, it decreased the levels of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and their respective receptors.

Conclusion: It is inferred that rolipram could exert neuroprotective effects by influencing neuronal signaling pathways implicated in MPTP/MPP+-induced Parkinson’s disease.

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/the-neuroprotective-effects-of-rolipram-a-selective-phosphodiesterase-iv-inhibitor-on-parkinsons-disease-in-rat-models-a-pharmacological-exploration-in-both-in-vivo-and-in-vitro-settings/