Behavioural inflexibility in a comorbid rat model of striatal ischemic injury and mutant hAPP overexpression
Alzheimer disease (AD) and stroke coexist and interact; yet how they interact is not sufficiently understood. Both AD and basal ganglia stroke can impair behavioural flexibility, which can be reliably modeled in rats using an established operant based set-shifting test. Transgenic Fischer 344-APP21...
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| Veröffentlicht in: | Behavioural brain research 2017-08, Vol.333, p.267-275 |
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| creator | Levit, Alexander Regis, Aaron M. Garabon, Jessica R. Oh, Seung-Hun Desai, Sagar J. Rajakumar, Nagalingam Hachinski, Vladimir Agca, Yuksel Agca, Cansu Whitehead, Shawn N. Allman, Brian L. |
| description | Alzheimer disease (AD) and stroke coexist and interact; yet how they interact is not sufficiently understood. Both AD and basal ganglia stroke can impair behavioural flexibility, which can be reliably modeled in rats using an established operant based set-shifting test. Transgenic Fischer 344-APP21 rats (TgF344) overexpress pathogenic human amyloid precursor protein (hAPP) but do not spontaneously develop overt pathology, hence TgF344 rats can be used to model the effect of vascular injury in the prodromal stages of Alzheimer disease. We demonstrate that the injection of endothelin-1 (ET1) into the dorsal striatum of TgF344 rats (Tg-ET1) produced an exacerbation of behavioural inflexibility with a behavioural phenotype that was distinct from saline-injected wildtype & TgF344 rats as well as ET1-injected wildtype rats (Wt-ET1). In addition to profiling the types of errors made, interpolative modeling using logistic exposure-response regression provided an informative analysis of the timing and efficiency of behavioural flexibility. During set-shifting, Tg-ET1 committed fewer perseverative errors than Wt-ET1. However, Tg-ET1 committed significantly more regressive errors and had a less efficient strategy change than all other groups. Thus, behavioural flexibility was more vulnerable to striatal ischemic injury in TgF344 rats. |
| doi_str_mv | 10.1016/j.bbr.2017.07.006 |
| format | Article |
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Both AD and basal ganglia stroke can impair behavioural flexibility, which can be reliably modeled in rats using an established operant based set-shifting test. Transgenic Fischer 344-APP21 rats (TgF344) overexpress pathogenic human amyloid precursor protein (hAPP) but do not spontaneously develop overt pathology, hence TgF344 rats can be used to model the effect of vascular injury in the prodromal stages of Alzheimer disease. We demonstrate that the injection of endothelin-1 (ET1) into the dorsal striatum of TgF344 rats (Tg-ET1) produced an exacerbation of behavioural inflexibility with a behavioural phenotype that was distinct from saline-injected wildtype & TgF344 rats as well as ET1-injected wildtype rats (Wt-ET1). In addition to profiling the types of errors made, interpolative modeling using logistic exposure-response regression provided an informative analysis of the timing and efficiency of behavioural flexibility. During set-shifting, Tg-ET1 committed fewer perseverative errors than Wt-ET1. However, Tg-ET1 committed significantly more regressive errors and had a less efficient strategy change than all other groups. Thus, behavioural flexibility was more vulnerable to striatal ischemic injury in TgF344 rats.</description><identifier>ISSN: 0166-4328</identifier><identifier>EISSN: 1872-7549</identifier><identifier>DOI: 10.1016/j.bbr.2017.07.006</identifier><identifier>PMID: 28693862</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Amyloid beta-Protein Precursor - genetics ; Amyloid beta-Protein Precursor - metabolism ; Amyloid precursor protein ; Analysis of Variance ; Animals ; Attention Deficit Disorder with Hyperactivity - etiology ; Behavioral flexibility ; Brain Ischemia - chemically induced ; Brain Ischemia - pathology ; Conditioning, Operant - physiology ; Corpus Striatum - drug effects ; Corpus Striatum - pathology ; Cues ; Discrimination (Psychology) - physiology ; Disease Models, Animal ; Endothelin-1 ; Endothelin-1 - toxicity ; Food Deprivation ; Humans ; Ischemic stroke ; Mental Disorders - etiology ; Mutation - genetics ; Rats ; Rats, Inbred F344 ; Rats, Transgenic ; Set-shifting ; Spatial Processing - physiology ; Transgenic rat</subject><ispartof>Behavioural brain research, 2017-08, Vol.333, p.267-275</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-c787246fc9ef378a657f74f68b54ac211281bf31114991ccf8f24f9875212e133</citedby><cites>FETCH-LOGICAL-c353t-c787246fc9ef378a657f74f68b54ac211281bf31114991ccf8f24f9875212e133</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0166432817304886$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28693862$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Levit, Alexander</creatorcontrib><creatorcontrib>Regis, Aaron M.</creatorcontrib><creatorcontrib>Garabon, Jessica R.</creatorcontrib><creatorcontrib>Oh, Seung-Hun</creatorcontrib><creatorcontrib>Desai, Sagar J.</creatorcontrib><creatorcontrib>Rajakumar, Nagalingam</creatorcontrib><creatorcontrib>Hachinski, Vladimir</creatorcontrib><creatorcontrib>Agca, Yuksel</creatorcontrib><creatorcontrib>Agca, Cansu</creatorcontrib><creatorcontrib>Whitehead, Shawn N.</creatorcontrib><creatorcontrib>Allman, Brian L.</creatorcontrib><title>Behavioural inflexibility in a comorbid rat model of striatal ischemic injury and mutant hAPP overexpression</title><title>Behavioural brain research</title><addtitle>Behav Brain Res</addtitle><description>Alzheimer disease (AD) and stroke coexist and interact; yet how they interact is not sufficiently understood. Both AD and basal ganglia stroke can impair behavioural flexibility, which can be reliably modeled in rats using an established operant based set-shifting test. Transgenic Fischer 344-APP21 rats (TgF344) overexpress pathogenic human amyloid precursor protein (hAPP) but do not spontaneously develop overt pathology, hence TgF344 rats can be used to model the effect of vascular injury in the prodromal stages of Alzheimer disease. We demonstrate that the injection of endothelin-1 (ET1) into the dorsal striatum of TgF344 rats (Tg-ET1) produced an exacerbation of behavioural inflexibility with a behavioural phenotype that was distinct from saline-injected wildtype & TgF344 rats as well as ET1-injected wildtype rats (Wt-ET1). In addition to profiling the types of errors made, interpolative modeling using logistic exposure-response regression provided an informative analysis of the timing and efficiency of behavioural flexibility. During set-shifting, Tg-ET1 committed fewer perseverative errors than Wt-ET1. However, Tg-ET1 committed significantly more regressive errors and had a less efficient strategy change than all other groups. Thus, behavioural flexibility was more vulnerable to striatal ischemic injury in TgF344 rats.</description><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloid precursor protein</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Attention Deficit Disorder with Hyperactivity - etiology</subject><subject>Behavioral flexibility</subject><subject>Brain Ischemia - chemically induced</subject><subject>Brain Ischemia - pathology</subject><subject>Conditioning, Operant - physiology</subject><subject>Corpus Striatum - drug effects</subject><subject>Corpus Striatum - pathology</subject><subject>Cues</subject><subject>Discrimination (Psychology) - physiology</subject><subject>Disease Models, Animal</subject><subject>Endothelin-1</subject><subject>Endothelin-1 - toxicity</subject><subject>Food Deprivation</subject><subject>Humans</subject><subject>Ischemic stroke</subject><subject>Mental Disorders - etiology</subject><subject>Mutation - genetics</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Rats, Transgenic</subject><subject>Set-shifting</subject><subject>Spatial Processing - physiology</subject><subject>Transgenic rat</subject><issn>0166-4328</issn><issn>1872-7549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE-LFDEQxYMo7uzqB_AiOXrpMZXuzh88rYuuwoJ70HNIpytMhu7OmKSHnW9vhlk9CgVFwe896j1C3gHbAgPxcb8dhrTlDOSW1WHiBdmAkryRfadfkk1lRNO1XF2R65z3jLGO9fCaXHEldKsE35DpM-7sMcQ12YmGxU_4FIYwhXKqF7XUxTmmIYw02ULnOOJEo6e5pGDLWZHdDufgKrxf04naZaTzWuxS6O728ZHGIyZ8OiTMOcTlDXnl7ZTx7fO-Ib--fvl59615-HH__e72oXFt35bGyZqhE95p9K1UVvTSy84LNfSddRyAKxh8CwCd1uCcV553XivZc-AIbXtDPlx8Dyn-XjEXM9dHcZrsgnHNBjRILaBnuqJwQV2KOSf05pDCbNPJADPnks3e1JLNuWTD6jBRNe-f7ddhxvGf4m-rFfh0AbCGPAZMJruAi8MxJHTFjDH8x_4PJViNjQ</recordid><startdate>20170830</startdate><enddate>20170830</enddate><creator>Levit, Alexander</creator><creator>Regis, Aaron M.</creator><creator>Garabon, Jessica R.</creator><creator>Oh, Seung-Hun</creator><creator>Desai, Sagar J.</creator><creator>Rajakumar, Nagalingam</creator><creator>Hachinski, Vladimir</creator><creator>Agca, Yuksel</creator><creator>Agca, Cansu</creator><creator>Whitehead, Shawn N.</creator><creator>Allman, Brian L.</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20170830</creationdate><title>Behavioural inflexibility in a comorbid rat model of striatal ischemic injury and mutant hAPP overexpression</title><author>Levit, Alexander ; Regis, Aaron M. ; Garabon, Jessica R. ; Oh, Seung-Hun ; Desai, Sagar J. ; Rajakumar, Nagalingam ; Hachinski, Vladimir ; Agca, Yuksel ; Agca, Cansu ; Whitehead, Shawn N. ; Allman, Brian L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-c787246fc9ef378a657f74f68b54ac211281bf31114991ccf8f24f9875212e133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Amyloid precursor protein</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Attention Deficit Disorder with Hyperactivity - etiology</topic><topic>Behavioral flexibility</topic><topic>Brain Ischemia - chemically induced</topic><topic>Brain Ischemia - pathology</topic><topic>Conditioning, Operant - physiology</topic><topic>Corpus Striatum - drug effects</topic><topic>Corpus Striatum - pathology</topic><topic>Cues</topic><topic>Discrimination (Psychology) - physiology</topic><topic>Disease Models, Animal</topic><topic>Endothelin-1</topic><topic>Endothelin-1 - toxicity</topic><topic>Food Deprivation</topic><topic>Humans</topic><topic>Ischemic stroke</topic><topic>Mental Disorders - etiology</topic><topic>Mutation - genetics</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Rats, Transgenic</topic><topic>Set-shifting</topic><topic>Spatial Processing - physiology</topic><topic>Transgenic rat</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Levit, Alexander</creatorcontrib><creatorcontrib>Regis, Aaron M.</creatorcontrib><creatorcontrib>Garabon, Jessica R.</creatorcontrib><creatorcontrib>Oh, Seung-Hun</creatorcontrib><creatorcontrib>Desai, Sagar J.</creatorcontrib><creatorcontrib>Rajakumar, Nagalingam</creatorcontrib><creatorcontrib>Hachinski, Vladimir</creatorcontrib><creatorcontrib>Agca, Yuksel</creatorcontrib><creatorcontrib>Agca, Cansu</creatorcontrib><creatorcontrib>Whitehead, Shawn N.</creatorcontrib><creatorcontrib>Allman, Brian L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Behavioural brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Levit, Alexander</au><au>Regis, Aaron M.</au><au>Garabon, Jessica R.</au><au>Oh, Seung-Hun</au><au>Desai, Sagar J.</au><au>Rajakumar, Nagalingam</au><au>Hachinski, Vladimir</au><au>Agca, Yuksel</au><au>Agca, Cansu</au><au>Whitehead, Shawn N.</au><au>Allman, Brian L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Behavioural inflexibility in a comorbid rat model of striatal ischemic injury and mutant hAPP overexpression</atitle><jtitle>Behavioural brain research</jtitle><addtitle>Behav Brain Res</addtitle><date>2017-08-30</date><risdate>2017</risdate><volume>333</volume><spage>267</spage><epage>275</epage><pages>267-275</pages><issn>0166-4328</issn><eissn>1872-7549</eissn><abstract>Alzheimer disease (AD) and stroke coexist and interact; yet how they interact is not sufficiently understood. Both AD and basal ganglia stroke can impair behavioural flexibility, which can be reliably modeled in rats using an established operant based set-shifting test. Transgenic Fischer 344-APP21 rats (TgF344) overexpress pathogenic human amyloid precursor protein (hAPP) but do not spontaneously develop overt pathology, hence TgF344 rats can be used to model the effect of vascular injury in the prodromal stages of Alzheimer disease. We demonstrate that the injection of endothelin-1 (ET1) into the dorsal striatum of TgF344 rats (Tg-ET1) produced an exacerbation of behavioural inflexibility with a behavioural phenotype that was distinct from saline-injected wildtype & TgF344 rats as well as ET1-injected wildtype rats (Wt-ET1). In addition to profiling the types of errors made, interpolative modeling using logistic exposure-response regression provided an informative analysis of the timing and efficiency of behavioural flexibility. During set-shifting, Tg-ET1 committed fewer perseverative errors than Wt-ET1. However, Tg-ET1 committed significantly more regressive errors and had a less efficient strategy change than all other groups. Thus, behavioural flexibility was more vulnerable to striatal ischemic injury in TgF344 rats.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28693862</pmid><doi>10.1016/j.bbr.2017.07.006</doi><tpages>9</tpages></addata></record> |
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| subjects | Amyloid beta-Protein Precursor - genetics Amyloid beta-Protein Precursor - metabolism Amyloid precursor protein Analysis of Variance Animals Attention Deficit Disorder with Hyperactivity - etiology Behavioral flexibility Brain Ischemia - chemically induced Brain Ischemia - pathology Conditioning, Operant - physiology Corpus Striatum - drug effects Corpus Striatum - pathology Cues Discrimination (Psychology) - physiology Disease Models, Animal Endothelin-1 Endothelin-1 - toxicity Food Deprivation Humans Ischemic stroke Mental Disorders - etiology Mutation - genetics Rats Rats, Inbred F344 Rats, Transgenic Set-shifting Spatial Processing - physiology Transgenic rat |
| title | Behavioural inflexibility in a comorbid rat model of striatal ischemic injury and mutant hAPP overexpression |
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