Chronic Anatabine Treatment Reduces Alzheimer's Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD
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 mous...
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| Veröffentlicht in: | PloS one 2015-05, Vol.10 (5), p.e0128224-e0128224 |
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| creator | Verma, Megha Beaulieu-Abdelahad, David Ait-Ghezala, Ghania Li, Rena Crawford, Fiona Mullan, Michael Paris, Daniel |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0128224 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0128224</identifier><identifier>PMID: 26010758</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alkaloids - pharmacology ; Alzheimer Disease - drug therapy ; Alzheimer Disease - genetics ; Alzheimer Disease - metabolism ; Alzheimer Disease - pathology ; Alzheimer's disease ; Alzheimers disease ; Amyloidosis ; Animal cognition ; Animals ; Anti-Alzheimer's disease agents ; Anti-inflammatory agents ; b-Site APP cleaving enzyme 1 ; Behavior ; Behavior, Animal - drug effects ; Brain ; Comparative analysis ; Complications and side effects ; Cyclooxygenase-2 ; Cytokines ; Disease Models, Animal ; Displays ; Dosage and administration ; Drinking water ; Drug therapy ; Gene expression ; Hyperactivity ; Inflammation ; Laboratory animals ; Medical treatment ; Memory ; Mice ; Mice, Transgenic ; Mutation ; Nerve Tissue Proteins - metabolism ; Neurodegenerative diseases ; NF-κB protein ; Nicotine ; Nitric-oxide synthase ; Pathology ; Peptides ; Phosphorylation ; Presenilin 1 ; Pyridines - pharmacology ; Receiving waters ; Reduction ; Rodents ; Social Behavior ; Stat3 protein ; Tau protein ; Tobacco ; Transgenic animals ; Transgenic mice ; β-Site APP-cleaving enzyme 1</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0128224-e0128224</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Verma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Verma et al 2015 Verma et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-eef1fb7be754163322dda8ae858b7dc38c04f27e39a54b139907014790df48aa3</citedby><cites>FETCH-LOGICAL-c692t-eef1fb7be754163322dda8ae858b7dc38c04f27e39a54b139907014790df48aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444019/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444019/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26010758$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Holscher, Christian</contributor><creatorcontrib>Verma, Megha</creatorcontrib><creatorcontrib>Beaulieu-Abdelahad, David</creatorcontrib><creatorcontrib>Ait-Ghezala, Ghania</creatorcontrib><creatorcontrib>Li, Rena</creatorcontrib><creatorcontrib>Crawford, Fiona</creatorcontrib><creatorcontrib>Mullan, Michael</creatorcontrib><creatorcontrib>Paris, Daniel</creatorcontrib><title>Chronic Anatabine Treatment Reduces Alzheimer's Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. 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metabolism</subject><subject>Neurodegenerative diseases</subject><subject>NF-κB protein</subject><subject>Nicotine</subject><subject>Nitric-oxide synthase</subject><subject>Pathology</subject><subject>Peptides</subject><subject>Phosphorylation</subject><subject>Presenilin 1</subject><subject>Pyridines - pharmacology</subject><subject>Receiving waters</subject><subject>Reduction</subject><subject>Rodents</subject><subject>Social Behavior</subject><subject>Stat3 protein</subject><subject>Tau protein</subject><subject>Tobacco</subject><subject>Transgenic animals</subject><subject>Transgenic mice</subject><subject>β-Site APP-cleaving enzyme 1</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk81u1DAUhSMEoqXwBggsIUG7mMGxncTZIA0dfkYqKmoLW-vGuZm4JPZgJxXlOXhgPO206qAuSBax7O-cGx_7JsnzlE5TXqRvz93oLXTTlbM4pSmTjIkHyW5acjbJGeUP74x3kichnFOacZnnj5MdltOUFpncTf4ctt5Zo8nMwgCVsUjOPMLQox3ICdajxkBm3e8WTY_-TSBzExACkv3Z_GByZH4g-QpD6zq3vCRga7LoV95dRNGp08ZN3mMLF8Z56MgcG6PNEIixBGIVsGGJ69Jf3BgNv7gaO-IaMps_TR410AV8tvnuJd8-fjg7_Dw5Ov60OJwdTXResmGC2KRNVVRYZCLNOWesrkECykxWRa251FQ0rEBeQiaqlJclLWgqipLWjZAAfC95ee276lxQm0CDSnPJeRHZLBKLa6J2cK5W3vTgL5UDo64mnF8q8IPRHSpaZrIsMgqMcyGzRsqKiZg3NA2WKHj0erepNlY91jomHGPZMt1esaZVS3ehRHxoPMu9ZH9j4N3PEcOgehM0dh1YjBFe_XeRlZkQEX31D3r_7jbUEuIGjG1crKvXpmomOIuRinLtNb2Him-NvdHx9jUmzm8JDrYEkRnw17CEMQS1OD35f_b4-zb7-g7bInRDG1w3DsbZsA2Ka1B7F4LH5jbklKp189ykodbNozbNE2Uv7h7QreimW_hfFXMTPg</recordid><startdate>20150526</startdate><enddate>20150526</enddate><creator>Verma, Megha</creator><creator>Beaulieu-Abdelahad, David</creator><creator>Ait-Ghezala, Ghania</creator><creator>Li, Rena</creator><creator>Crawford, Fiona</creator><creator>Mullan, Michael</creator><creator>Paris, Daniel</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150526</creationdate><title>Chronic Anatabine Treatment Reduces Alzheimer's Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD</title><author>Verma, Megha ; Beaulieu-Abdelahad, David ; Ait-Ghezala, Ghania ; Li, Rena ; Crawford, Fiona ; Mullan, Michael ; Paris, Daniel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-eef1fb7be754163322dda8ae858b7dc38c04f27e39a54b139907014790df48aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Alkaloids - pharmacology</topic><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - genetics</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer's disease</topic><topic>Alzheimers disease</topic><topic>Amyloidosis</topic><topic>Animal cognition</topic><topic>Animals</topic><topic>Anti-Alzheimer's disease agents</topic><topic>Anti-inflammatory agents</topic><topic>b-Site APP cleaving enzyme 1</topic><topic>Behavior</topic><topic>Behavior, Animal - drug effects</topic><topic>Brain</topic><topic>Comparative analysis</topic><topic>Complications and side effects</topic><topic>Cyclooxygenase-2</topic><topic>Cytokines</topic><topic>Disease Models, Animal</topic><topic>Displays</topic><topic>Dosage and administration</topic><topic>Drinking water</topic><topic>Drug therapy</topic><topic>Gene expression</topic><topic>Hyperactivity</topic><topic>Inflammation</topic><topic>Laboratory animals</topic><topic>Medical treatment</topic><topic>Memory</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Mutation</topic><topic>Nerve Tissue Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Verma, Megha</au><au>Beaulieu-Abdelahad, David</au><au>Ait-Ghezala, Ghania</au><au>Li, Rena</au><au>Crawford, Fiona</au><au>Mullan, Michael</au><au>Paris, Daniel</au><au>Holscher, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chronic Anatabine Treatment Reduces Alzheimer's Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-26</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0128224</spage><epage>e0128224</epage><pages>e0128224-e0128224</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26010758</pmid><doi>10.1371/journal.pone.0128224</doi><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_1683370705 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Alkaloids - pharmacology Alzheimer Disease - drug therapy Alzheimer Disease - genetics Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer's disease Alzheimers disease Amyloidosis Animal cognition Animals Anti-Alzheimer's disease agents Anti-inflammatory agents b-Site APP cleaving enzyme 1 Behavior Behavior, Animal - drug effects Brain Comparative analysis Complications and side effects Cyclooxygenase-2 Cytokines Disease Models, Animal Displays Dosage and administration Drinking water Drug therapy Gene expression Hyperactivity Inflammation Laboratory animals Medical treatment Memory Mice Mice, Transgenic Mutation Nerve Tissue Proteins - metabolism Neurodegenerative diseases NF-κB protein Nicotine Nitric-oxide synthase Pathology Peptides Phosphorylation Presenilin 1 Pyridines - pharmacology Receiving waters Reduction Rodents Social Behavior Stat3 protein Tau protein Tobacco Transgenic animals Transgenic mice β-Site APP-cleaving enzyme 1 |
| title | Chronic Anatabine Treatment Reduces Alzheimer's Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T21%3A26%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Chronic%20Anatabine%20Treatment%20Reduces%20Alzheimer's%20Disease%20(AD)-Like%20Pathology%20and%20Improves%20Socio-Behavioral%20Deficits%20in%20a%20Transgenic%20Mouse%20Model%20of%20AD&rft.jtitle=PloS%20one&rft.au=Verma,%20Megha&rft.date=2015-05-26&rft.volume=10&rft.issue=5&rft.spage=e0128224&rft.epage=e0128224&rft.pages=e0128224-e0128224&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0128224&rft_dat=%3Cgale_plos_%3EA432633494%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1683370705&rft_id=info:pmid/26010758&rft_galeid=A432633494&rft_doaj_id=oai_doaj_org_article_09589750a233485f88b24386affe9e43&rfr_iscdi=true |