Chronic Anatabine Treatment Reduces Alzheimer’s Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD
Megha Verma
David Beaulieu-Abdelahad
Ghania Ait-Ghezala
Rena Li
Fiona Crawford
Michael Mullan
Daniel Paris
10.1371/journal.pone.0128224
https://plos.figshare.com/articles/dataset/_Chronic_Anatabine_Treatment_Reduces_Alzheimer_8217_s_Disease_AD_Like_Pathology_and_Improves_Socio_Behavioral_Deficits_in_a_Transgenic_Mouse_Model_of_AD_/1425762
<div><p>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 <i>Bace1</i>, <i>iNOS</i> and <i>Cox-2</i>. 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.</p></div>
2015-05-26 15:04:00
anatabine treatment
stat
ad
ps
nf
Chronic Anatabine Treatment
chemical structure similarity
Mouse Model
β deposits
tg
Transgenic Mouse Model