Roflumilast Attenuates Neuroinflammation and Cognitive Impairment in Intracerbroventricular-Streptozotocin Induced Rat Model of Sporadic Alzheimer’s Disease through Modulation of cAMP/BDNF Signaling Pathway
Journal Title: The 2nd Annual Meeting of International Center for Neuroscience Research - Year 2021, Vol 2, Issue 1
Abstract
Sporadic Alzheimer’s disease (SAD) is the most complex and multifactorial neurodegenerative disease characterized by progressive cognitive deficits and memory loss. Phosphodiesterase (PDE) inhibitors prevent the breakdown of cAMP in the brain, which is an important intracellular secondary messenger for learning and memory functions. Thus, the present study was designed to explore the therapeutic potential of PDE-4 inhibitor roflumilast (RFM) against intracerebroventricular-streptozotocin (ICV-STZ) induced SAD in rats. Subsequently, in vivo study was performed in which rats were infused intracerebroventricularly with two alternate doses of STZ (3 mg/kg bilaterally) proceeding with RFM (0.05 mg/kg orally) treatment for 15 days. Moreover, donepezil, an acetylcholinesterase inhibitor (5 mg/kg orally) was used as a standard drug. Consequently, we observed that RFM significantly improved the ICV-STZ impaired cognitive function in rats as assessed by novel object recognition and Morris Water Maze outcomes. RFM was found to remarkably mitigate the ICV-STZ triggered cholinergic deficits, neuroinflammation, oxidative stress, in rat hippocampus. Supporting these, histopathological analysis using Cresyl violet, and Congo red revealed that RFM attenuated neuronal changes, and Aβ deposition respectively in hippocampus of SAD rats. These outcomes present RFM as an efficient target for the treatment of SAD through activation of cAMP/BDNF signaling pathway.
Authors and Affiliations
Noorul Hasan, Abul Kalam Najmi, Suhel Parvez, Mohd Akhtar*
Keywords
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