The impact of 6-hydroxy-L-nicotine on inflammation in a 5xFAD mouse model of Alzheimer’s disease
Alexandra Mara Cimpanu1, Lucian Hritcu1, Razvan Stefan Boiangiu1
1BioActive Research Group, Department of Biology, Alexandru Ioan Cuza University of Iasi, Romania
Introduction: Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia. AD patients suffer from memory loss, aphasia, and personality and behavior changes and exhibit difficulties in thinking, language, and problem-solving skills. The main neuropathologic features of AD include extracellular plaques containing amyloid beta (Aβ) and intracellular neurofibrillary tangles of hyperphosphorylated tau protein. In addition to these essential features, several other pathologic changes such as inflammation and the sustained activation of microglia and other immune cells are commonly associated with AD. Nicotine has been reported to reduce anxiety and improve memory, learning, and attention, but its therapeutic use in AD is limited by its side effects. Here, we aim to evaluate the anti-inflammatory effect of a structure-related nicotine derivative, namely 6-hydroxy-L-nicotine (6HLN), in a transgenic mouse model of AD.
Methods: 6HLN was chronically administered in doses of 0.3 and 0.6 mg/kg (b.w., i.p., for 30 days) to a 5xFAD mouse model of AD. By using ELISA, we measured the levels of glial fibrillary acidic protein (GFAP), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) in the brains of the 6HLN-treated mice.
Results: Our results showed that 6HLN treatment reduced, in a dose-dependent manner, the levels of GFAP, NF-kB, IL-6, and TNF-α in the brain of the transgenic mouse model of AD, indicating a promising anti-inflammatory potential of 6HLN.
Conclusion: These findings are in accordance with those from the literature, indicating that 6HLN might represent a new neuropharmacological agent in ameliorating AD. This work was supported by CNCSIS-UEFISCSU, project number PN-III-P4-PCE-2021-1692.
