Anatabine is a minor tobacco
alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with
nicotine. We have shown previously that
anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of
tauopathy. We therefore investigated the effects of a chronic oral treatment with
anatabine in a transgenic mouse model (Tg PS1/APPswe) of
Alzheimer's disease (AD) which displays pathological Aβ deposits,
neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral
anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular
drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social
memory deficits, which were both alleviated by the
anatabine treatment. We found that
anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with
anatabine. This is the first study to investigate the impact of chronic
anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that
anatabine reduces β-
amyloidosis,
neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of
anatabine as a possible disease modifying agent for the treatment of AD.