Objective: Rolipram, a specific inhibitor of the phosphodiesterase IV (PDE IV), has recently been shown to exert neuroprotective effects in an Alzheimer transgenic mouse model and in hypoxic-ischemic damage in the rat brain. It activates the cAMP-dependent protein kinase (PKA)/cAMP regulatory element-binding protein (CREB) signaling pathway and it inhibits inflammation.  The cAMP mediated signaling is regulated by the activity of cyclic nucleotide phosphodiesterases (PDE) that cleave the second messenger. In the present study, we tested neuroprotective effects, if any, of rolipram drug, a specific inhibitor of the phosphodiesterase IV in 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice.

Background: Parkinson’s disease (PD) is a neurodegenerative disease and a movement disorder characterized by loss of dopaminergic neurons in the substantia nigra causing dopamine depletion in the striatum. 

Methods: Experimental animal is muscular weighing 25–30 g of 4–5-month-old. The drug was given four times at 12 h intervals by gavation (25–100 mg/kg) in animals made parkinsonian following two doses of MPTP (30 mg/kg, i.p.). Control mice were injected with the same volume of pure DMSO. MPTP-induced striatal dopamine depletion was significantly attenuated by higher dose of rolipram. MPTP-induced catalepsy and akinesia, as well as loss in swim ability, were blocked dose-dependently by rolipram. Brain was used for biochemical and histopathological study.

Results: Present study further shows that rolipram can dose-dependently attenuate both in vitro hydroxyl radical production in a Fenton-like reaction, and also ex vivo 1-methyl-4-phenylpyridinium (MPP+)-induced hydroxyl radical generation in isolated mitochondria. These results indicate that the observed neuroprotective effects of rolipram stem from its significant antioxidant action.

Conclusions: The preliminary results suggest that rolipram is a neuroprotector, and mechanism other than lipid lowering action could be the basis of this effect. Present data show a neuroprotective effect of the PDE IV specific inhibitor rolipram against dopaminergic neuron degeneration, suggesting that PDE IV inhibitors might be a potential treatment for Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/rolipram-a-pde-iv-inhibitor-protects-against-experimental-parkinsonism-in-mice/