Nisha Kumari, Shivam Kumar Pandey, Mohammed Zunaid Akhtar, Mangaldeep Dey, Avtar Singh Gautam, Anjuman Nanda, Aman Tiwari, Rakesh Kumar Singh
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引用次数: 0
Abstract
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.
期刊介绍:
Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer''s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ''bird''s-eye view'' of the current state of Alzheimer''s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.