Ameliorative Effects of Telmisartan on the Inflammatory Response and Impaired Spatial Memory in a Rat Model of Alzheimer's Disease Incorporating Additional Cerebrovascular Disease Factors
Telmisartan, an angiotensin type 1 receptor blocker, is used in the management of hypertension to control blood pressure. In addition, telmisartan has a partial agonistic effect on peroxisome proliferator activated receptor γ (PPARγ). Recently, the effects of telmisartan on spatial memory or the inf...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2012/12/01, Vol.35(12), pp.2141-2147 |
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| creator | Shindo, Taro Takasaki, Kotaro Uchida, Kanako Onimura, Rika Kubota, Kaori Uchida, Naoki Irie, Keiichi Katsurabayashi, Shutaro Mishima, Kenichi Nishimura, Ryoji Fujiwara, Michihiro Iwasaki, Katsunori |
| description | Telmisartan, an angiotensin type 1 receptor blocker, is used in the management of hypertension to control blood pressure. In addition, telmisartan has a partial agonistic effect on peroxisome proliferator activated receptor γ (PPARγ). Recently, the effects of telmisartan on spatial memory or the inflammatory response were monitored in a mouse model of Alzheimer's disease (AD). However, to date, no studies have investigated the ameliorative effects of telmisartan on impaired spatial memory and the inflammatory response in an AD animal model incorporating additional cerebrovascular disease factors. In this study, we examined the effect of telmisartan on spatial memory impairment and the inflammatory response in a rat model of AD incorporating additional cerebrovascular disease factors. Rats were subjected to cerebral ischemia and an intracerebroventricular injection of oligomeric or aggregated amyloid-β (Aβ). Oral administration of telmisartan (0.3, 1, 3 mg/kg/d) seven days after ischemia and Aβ treatment resulted in better performance in the eight arm radial maze task in a dose-dependent manner. Telmisartan also reduced tumor necrosis factor α mRNA expression in the hippocampal region of rats with impaired spatial memory. These effects of telmisartan were antagonized by GW9662, an antagonist of PPARγ. These results suggest that telmisartan has ameliorative effects on the impairment of spatial memory in a rat model of AD incorporating additional cerebrovascular disease factors via its anti-inflammatory effect. |
| doi_str_mv | 10.1248/bpb.b12-00387 |
| format | Article |
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In addition, telmisartan has a partial agonistic effect on peroxisome proliferator activated receptor γ (PPARγ). Recently, the effects of telmisartan on spatial memory or the inflammatory response were monitored in a mouse model of Alzheimer's disease (AD). However, to date, no studies have investigated the ameliorative effects of telmisartan on impaired spatial memory and the inflammatory response in an AD animal model incorporating additional cerebrovascular disease factors. In this study, we examined the effect of telmisartan on spatial memory impairment and the inflammatory response in a rat model of AD incorporating additional cerebrovascular disease factors. Rats were subjected to cerebral ischemia and an intracerebroventricular injection of oligomeric or aggregated amyloid-β (Aβ). Oral administration of telmisartan (0.3, 1, 3 mg/kg/d) seven days after ischemia and Aβ treatment resulted in better performance in the eight arm radial maze task in a dose-dependent manner. Telmisartan also reduced tumor necrosis factor α mRNA expression in the hippocampal region of rats with impaired spatial memory. These effects of telmisartan were antagonized by GW9662, an antagonist of PPARγ. These results suggest that telmisartan has ameliorative effects on the impairment of spatial memory in a rat model of AD incorporating additional cerebrovascular disease factors via its anti-inflammatory effect.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b12-00387</identifier><identifier>PMID: 23207766</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Alzheimer disease ; Alzheimer Disease - complications ; Alzheimer Disease - drug therapy ; Alzheimer Disease - metabolism ; Amyloid - adverse effects ; Angiotensin II Type 1 Receptor Blockers - pharmacology ; Angiotensin II Type 1 Receptor Blockers - therapeutic use ; Anilides - pharmacology ; Animals ; Anti-Inflammatory Agents - pharmacology ; Anti-Inflammatory Agents - therapeutic use ; Benzimidazoles - pharmacology ; Benzimidazoles - therapeutic use ; Benzoates - pharmacology ; Benzoates - therapeutic use ; Brain Ischemia - complications ; Brain Ischemia - drug therapy ; Brain Ischemia - metabolism ; Cerebrovascular Disorders - complications ; Cerebrovascular Disorders - drug therapy ; Cerebrovascular Disorders - metabolism ; Cerebrum - drug effects ; Cerebrum - pathology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Hippocampus - drug effects ; Hippocampus - metabolism ; Inflammation - drug therapy ; Inflammation - etiology ; Inflammation - metabolism ; inflammatory ; Male ; Maze Learning - drug effects ; Memory - drug effects ; Memory Disorders - drug therapy ; Memory Disorders - etiology ; Memory Disorders - metabolism ; PPAR gamma - metabolism ; rat ; Rats ; Rats, Wistar ; Telmisartan ; tumor necrosis factor α ; Tumor Necrosis Factor-alpha - genetics ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Biological and Pharmaceutical Bulletin, 2012/12/01, Vol.35(12), pp.2141-2147</ispartof><rights>2012 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c736t-a04aa661122cd551b4ff0868a1db91a9d4effb9058fc5a1a8866f7d93f2362703</citedby><cites>FETCH-LOGICAL-c736t-a04aa661122cd551b4ff0868a1db91a9d4effb9058fc5a1a8866f7d93f2362703</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,1877,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23207766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shindo, Taro</creatorcontrib><creatorcontrib>Takasaki, Kotaro</creatorcontrib><creatorcontrib>Uchida, Kanako</creatorcontrib><creatorcontrib>Onimura, Rika</creatorcontrib><creatorcontrib>Kubota, Kaori</creatorcontrib><creatorcontrib>Uchida, Naoki</creatorcontrib><creatorcontrib>Irie, Keiichi</creatorcontrib><creatorcontrib>Katsurabayashi, Shutaro</creatorcontrib><creatorcontrib>Mishima, Kenichi</creatorcontrib><creatorcontrib>Nishimura, Ryoji</creatorcontrib><creatorcontrib>Fujiwara, Michihiro</creatorcontrib><creatorcontrib>Iwasaki, Katsunori</creatorcontrib><creatorcontrib>Faculty of Medicine</creatorcontrib><creatorcontrib>Fukuoka University</creatorcontrib><creatorcontrib>Department of Neuropharmacology</creatorcontrib><creatorcontrib>Faculty of Pharmaceutical Science</creatorcontrib><creatorcontrib>Department of Psychiatry</creatorcontrib><title>Ameliorative Effects of Telmisartan on the Inflammatory Response and Impaired Spatial Memory in a Rat Model of Alzheimer's Disease Incorporating Additional Cerebrovascular Disease Factors</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Telmisartan, an angiotensin type 1 receptor blocker, is used in the management of hypertension to control blood pressure. In addition, telmisartan has a partial agonistic effect on peroxisome proliferator activated receptor γ (PPARγ). Recently, the effects of telmisartan on spatial memory or the inflammatory response were monitored in a mouse model of Alzheimer's disease (AD). However, to date, no studies have investigated the ameliorative effects of telmisartan on impaired spatial memory and the inflammatory response in an AD animal model incorporating additional cerebrovascular disease factors. In this study, we examined the effect of telmisartan on spatial memory impairment and the inflammatory response in a rat model of AD incorporating additional cerebrovascular disease factors. Rats were subjected to cerebral ischemia and an intracerebroventricular injection of oligomeric or aggregated amyloid-β (Aβ). Oral administration of telmisartan (0.3, 1, 3 mg/kg/d) seven days after ischemia and Aβ treatment resulted in better performance in the eight arm radial maze task in a dose-dependent manner. Telmisartan also reduced tumor necrosis factor α mRNA expression in the hippocampal region of rats with impaired spatial memory. These effects of telmisartan were antagonized by GW9662, an antagonist of PPARγ. These results suggest that telmisartan has ameliorative effects on the impairment of spatial memory in a rat model of AD incorporating additional cerebrovascular disease factors via its anti-inflammatory effect.</description><subject>Alzheimer disease</subject><subject>Alzheimer Disease - complications</subject><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - metabolism</subject><subject>Amyloid - adverse effects</subject><subject>Angiotensin II Type 1 Receptor Blockers - pharmacology</subject><subject>Angiotensin II Type 1 Receptor Blockers - therapeutic use</subject><subject>Anilides - pharmacology</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Benzimidazoles - pharmacology</subject><subject>Benzimidazoles - therapeutic use</subject><subject>Benzoates - pharmacology</subject><subject>Benzoates - therapeutic use</subject><subject>Brain Ischemia - complications</subject><subject>Brain Ischemia - drug therapy</subject><subject>Brain Ischemia - metabolism</subject><subject>Cerebrovascular Disorders - complications</subject><subject>Cerebrovascular Disorders - drug therapy</subject><subject>Cerebrovascular Disorders - metabolism</subject><subject>Cerebrum - drug effects</subject><subject>Cerebrum - pathology</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - etiology</subject><subject>Inflammation - metabolism</subject><subject>inflammatory</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>Memory - drug effects</subject><subject>Memory Disorders - drug therapy</subject><subject>Memory Disorders - etiology</subject><subject>Memory Disorders - metabolism</subject><subject>PPAR gamma - metabolism</subject><subject>rat</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Telmisartan</subject><subject>tumor necrosis factor α</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAUhSMEokNhyRZZYlE2Kf5JHGc5mv4wUiukUtbRjXPd8ciJg52pVF6Nl8OZKYPEBi_shT9_Pk5Olr1n9JzxQn1ux_a8ZTynVKjqRbZgoqjykrPyZbagNVO5ZKU6yd7EuKWUVpSL19kJF5xWlZSL7NeyR2d9gMk-Irk0BvUUiTfkHl1vI4QJBuIHMm2QrAfjoO9h8uGJ3GEc_RCRwNCRdT-CDdiRb2MSgSO32M-QHQiQO5jIre_Qzdql-7lB22M4i-TCRoQ4e7UP4z7D8ECWXWcn64dkWWHANvhHiHrnIBwPXIFOGeLb7JUBF_Hd83qafb-6vF99yW--Xq9Xy5tcV0JOOdACQErGONddWbK2MIYqqYB1bc2g7go0pq1pqYwugYFSUpqqq4XhQvKKitPs08E7Bv9jh3Fq0pfR6BwM6HexYQWrRSXKWv4f5WkIxlSV0I__oFu_C-nZs7CohWJ1USYqP1A6-BgDmmYMtofw1DDazAVoUgGaVIBmX4DEf3i27toeuyP9548n4PoApF2rwfnB2QH_3q1j1VrvfMPpQVruF9nw9Mx5qpiqWS1VMl0cTNs4wQMer0qdsdrhPpgoU8h5PiY8busNhAYH8Rs1Htyu</recordid><startdate>20121201</startdate><enddate>20121201</enddate><creator>Shindo, Taro</creator><creator>Takasaki, Kotaro</creator><creator>Uchida, Kanako</creator><creator>Onimura, Rika</creator><creator>Kubota, Kaori</creator><creator>Uchida, Naoki</creator><creator>Irie, Keiichi</creator><creator>Katsurabayashi, Shutaro</creator><creator>Mishima, Kenichi</creator><creator>Nishimura, Ryoji</creator><creator>Fujiwara, Michihiro</creator><creator>Iwasaki, Katsunori</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20121201</creationdate><title>Ameliorative Effects of Telmisartan on the Inflammatory Response and Impaired Spatial Memory in a Rat Model of Alzheimer's Disease Incorporating Additional Cerebrovascular Disease Factors</title><author>Shindo, Taro ; Takasaki, Kotaro ; Uchida, Kanako ; Onimura, Rika ; Kubota, Kaori ; Uchida, Naoki ; Irie, Keiichi ; Katsurabayashi, Shutaro ; Mishima, Kenichi ; Nishimura, Ryoji ; Fujiwara, Michihiro ; Iwasaki, Katsunori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c736t-a04aa661122cd551b4ff0868a1db91a9d4effb9058fc5a1a8866f7d93f2362703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Alzheimer disease</topic><topic>Alzheimer Disease - 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drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - etiology</topic><topic>Inflammation - metabolism</topic><topic>inflammatory</topic><topic>Male</topic><topic>Maze Learning - drug effects</topic><topic>Memory - drug effects</topic><topic>Memory Disorders - drug therapy</topic><topic>Memory Disorders - etiology</topic><topic>Memory Disorders - metabolism</topic><topic>PPAR gamma - metabolism</topic><topic>rat</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Telmisartan</topic><topic>tumor necrosis factor α</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shindo, Taro</creatorcontrib><creatorcontrib>Takasaki, Kotaro</creatorcontrib><creatorcontrib>Uchida, Kanako</creatorcontrib><creatorcontrib>Onimura, Rika</creatorcontrib><creatorcontrib>Kubota, Kaori</creatorcontrib><creatorcontrib>Uchida, Naoki</creatorcontrib><creatorcontrib>Irie, Keiichi</creatorcontrib><creatorcontrib>Katsurabayashi, Shutaro</creatorcontrib><creatorcontrib>Mishima, Kenichi</creatorcontrib><creatorcontrib>Nishimura, Ryoji</creatorcontrib><creatorcontrib>Fujiwara, Michihiro</creatorcontrib><creatorcontrib>Iwasaki, Katsunori</creatorcontrib><creatorcontrib>Faculty of Medicine</creatorcontrib><creatorcontrib>Fukuoka University</creatorcontrib><creatorcontrib>Department of Neuropharmacology</creatorcontrib><creatorcontrib>Faculty of Pharmaceutical Science</creatorcontrib><creatorcontrib>Department of Psychiatry</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - 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In addition, telmisartan has a partial agonistic effect on peroxisome proliferator activated receptor γ (PPARγ). Recently, the effects of telmisartan on spatial memory or the inflammatory response were monitored in a mouse model of Alzheimer's disease (AD). However, to date, no studies have investigated the ameliorative effects of telmisartan on impaired spatial memory and the inflammatory response in an AD animal model incorporating additional cerebrovascular disease factors. In this study, we examined the effect of telmisartan on spatial memory impairment and the inflammatory response in a rat model of AD incorporating additional cerebrovascular disease factors. Rats were subjected to cerebral ischemia and an intracerebroventricular injection of oligomeric or aggregated amyloid-β (Aβ). Oral administration of telmisartan (0.3, 1, 3 mg/kg/d) seven days after ischemia and Aβ treatment resulted in better performance in the eight arm radial maze task in a dose-dependent manner. Telmisartan also reduced tumor necrosis factor α mRNA expression in the hippocampal region of rats with impaired spatial memory. These effects of telmisartan were antagonized by GW9662, an antagonist of PPARγ. These results suggest that telmisartan has ameliorative effects on the impairment of spatial memory in a rat model of AD incorporating additional cerebrovascular disease factors via its anti-inflammatory effect.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>23207766</pmid><doi>10.1248/bpb.b12-00387</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Biological and Pharmaceutical Bulletin, 2012/12/01, Vol.35(12), pp.2141-2147 |
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| source | J-STAGE Free; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | Alzheimer disease Alzheimer Disease - complications Alzheimer Disease - drug therapy Alzheimer Disease - metabolism Amyloid - adverse effects Angiotensin II Type 1 Receptor Blockers - pharmacology Angiotensin II Type 1 Receptor Blockers - therapeutic use Anilides - pharmacology Animals Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Benzimidazoles - pharmacology Benzimidazoles - therapeutic use Benzoates - pharmacology Benzoates - therapeutic use Brain Ischemia - complications Brain Ischemia - drug therapy Brain Ischemia - metabolism Cerebrovascular Disorders - complications Cerebrovascular Disorders - drug therapy Cerebrovascular Disorders - metabolism Cerebrum - drug effects Cerebrum - pathology Disease Models, Animal Dose-Response Relationship, Drug Hippocampus - drug effects Hippocampus - metabolism Inflammation - drug therapy Inflammation - etiology Inflammation - metabolism inflammatory Male Maze Learning - drug effects Memory - drug effects Memory Disorders - drug therapy Memory Disorders - etiology Memory Disorders - metabolism PPAR gamma - metabolism rat Rats Rats, Wistar Telmisartan tumor necrosis factor α Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - metabolism |
| title | Ameliorative Effects of Telmisartan on the Inflammatory Response and Impaired Spatial Memory in a Rat Model of Alzheimer's Disease Incorporating Additional Cerebrovascular Disease Factors |
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