Background:
Microglial overactivation promotes the production of various second messengers and inflammatory markers in brain tissue, resulting in neuroinflammation and neurodegeneration, which may lead to cognitive decline. The cyclic nucleotides are one of the important second
messengers involved in the regulation of neurogenesis, synaptic plasticity, and cognition. The levels
of these cyclic nucleotides are maintained by phosphodiesterase enzyme isoforms, particularly
PDE4B, in the brain. An imbalance between PDE4B levels and cyclic nucleotides may lead to aggravating neuroinflammation.
Methods:
Lipopolysaccharides (LPS) were administered intraperitoneally on alternate days for 7 days
at a dose of 500 µg/kg in mice, which triggered systemic inflammation. This may lead to the activation of glial cells and may activate oxidative stress and neuroinflammatory markers in brain tissue.
Furthermore, oral administration of roflumilast (0.1, 0.2, and 0.4 mg/kg) in this model ameliorated
oxidative stress markers, neuroinflammation and improved neurobehavioral parameters in these animals.
Results:
The detrimental effect of LPS increased oxidative stress, AChE enzyme levels, and decreased catalase levels in brain tissues, along with memory impairment in animals. Moreover, it also
enhanced the activity and expression of the PDE4B enzyme, resulting in a decline in cyclic nucleotide
levels. Furthermore, treatment with roflumilast improved the cognitive decline, decreased AChE enzyme level, and increased the catalase enzyme level. Roflumilast also reduced the PDE4B expression
in a dose-dependent manner, which LPS up-regulated.
Conclusion:
Roflumilast has shown an anti-neuroinflammatory effect and reversed the cognitive decline in LPS-induced mice model.
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