Synergistic effect of galantamine on nicotine-induced neuroprotection in hemiparkinsonian rat model
Recent studies have reported that smokers tend to be less susceptible to Parkinson’s disease (PD) and the stimulation of nicotinic acetylcholine receptor (nAChR) is considered to confer a neuroprotective effect. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiating ligand f...
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| Veröffentlicht in: | Neuroscience research 2008-12, Vol.62 (4), p.254-261 |
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| creator | Yanagida, Takashi Takeuchi, Hiroki Kitamura, Yoshihisa Takata, Kazuyuki Minamino, Hideaki Shibaike, Tomonori Tsushima, Jun Kishimoto, Koji Yasui, Hiroyuki Taniguchi, Takashi Shimohama, Shun |
| description | Recent studies have reported that smokers tend to be less susceptible to Parkinson’s disease (PD) and the stimulation of nicotinic acetylcholine receptor (nAChR) is considered to confer a neuroprotective effect. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiating ligand for nAChRs. However, the effects of galantamine and nicotine on dopaminergic neurons remain unclear. This study evaluated the neuroprotective effects of galantamine and nicotine in a rat 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian model. 6-OHDA with or without galantamine and/or nicotine were injected into unilateral substantia nigra of rats. Although methamphetamine-stimulated rotational behavior and dopaminergic neuronal loss induced by 6-OHDA were not inhibited by galantamine alone, those were moderately inhibited by nicotine alone. In addition, 6-OHDA-induced neuronal loss and rotational behavior were synergistically inhibited by co-injection of galantamine and nicotine. These protective effects were abolished by mecamylamine, an nAChR antagonist. We further found that α7 nAChR was expressed on both tyrosine hydroxylase (TH)-immunopositive and TH-immunonegative neurons in the SNpc. A combination of galantamine and nicotine greatly suppressed 6-OHDA-induced reduction of TH-immunopositive/α7 nAChR-immunopositive neurons. These results suggest that galantamine synergistically enhances the neuroprotective effect of nicotine against 6-OHDA-induced dopaminergic neuronal loss through an allosteric modulation of α7 nAChR activation. |
| doi_str_mv | 10.1016/j.neures.2008.09.003 |
| format | Article |
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Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiating ligand for nAChRs. However, the effects of galantamine and nicotine on dopaminergic neurons remain unclear. This study evaluated the neuroprotective effects of galantamine and nicotine in a rat 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian model. 6-OHDA with or without galantamine and/or nicotine were injected into unilateral substantia nigra of rats. Although methamphetamine-stimulated rotational behavior and dopaminergic neuronal loss induced by 6-OHDA were not inhibited by galantamine alone, those were moderately inhibited by nicotine alone. In addition, 6-OHDA-induced neuronal loss and rotational behavior were synergistically inhibited by co-injection of galantamine and nicotine. These protective effects were abolished by mecamylamine, an nAChR antagonist. We further found that α7 nAChR was expressed on both tyrosine hydroxylase (TH)-immunopositive and TH-immunonegative neurons in the SNpc. A combination of galantamine and nicotine greatly suppressed 6-OHDA-induced reduction of TH-immunopositive/α7 nAChR-immunopositive neurons. These results suggest that galantamine synergistically enhances the neuroprotective effect of nicotine against 6-OHDA-induced dopaminergic neuronal loss through an allosteric modulation of α7 nAChR activation.</description><identifier>ISSN: 0168-0102</identifier><identifier>EISSN: 1872-8111</identifier><identifier>DOI: 10.1016/j.neures.2008.09.003</identifier><identifier>PMID: 18845194</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>6-Hydroxydopamine ; Allosteric potentiating ligand ; alpha7 Nicotinic Acetylcholine Receptor ; Animals ; Disease Models, Animal ; Dopamine Uptake Inhibitors - pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Electron Spin Resonance Spectroscopy - methods ; Functional Laterality ; Galantamine ; Galantamine - therapeutic use ; Gene Expression Regulation - drug effects ; Male ; Mecamylamine - pharmacology ; Methamphetamine - pharmacology ; Motor Activity - drug effects ; Neuroprotective Agents - therapeutic use ; Nicotine - therapeutic use ; Nicotinic acetylcholine receptor ; Nicotinic Antagonists - pharmacology ; Parkinsonian Disorders - drug therapy ; Parkinsonian Disorders - etiology ; Parkinsonian Disorders - metabolism ; Parkinson’s disease ; Rats ; Rats, Wistar ; Receptors, Nicotinic - genetics ; Receptors, Nicotinic - metabolism ; RNA, Messenger - metabolism ; Rotarod Performance Test ; Tyrosine 3-Monooxygenase - metabolism</subject><ispartof>Neuroscience research, 2008-12, Vol.62 (4), p.254-261</ispartof><rights>2008 Elsevier Ireland Ltd and the Japan Neuroscience Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-c5395c8480c68546d9947803c2de75fcc2baf526dc5ea2bfcff9c7e6731bd53d3</citedby><cites>FETCH-LOGICAL-c481t-c5395c8480c68546d9947803c2de75fcc2baf526dc5ea2bfcff9c7e6731bd53d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neures.2008.09.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18845194$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yanagida, Takashi</creatorcontrib><creatorcontrib>Takeuchi, Hiroki</creatorcontrib><creatorcontrib>Kitamura, Yoshihisa</creatorcontrib><creatorcontrib>Takata, Kazuyuki</creatorcontrib><creatorcontrib>Minamino, Hideaki</creatorcontrib><creatorcontrib>Shibaike, Tomonori</creatorcontrib><creatorcontrib>Tsushima, Jun</creatorcontrib><creatorcontrib>Kishimoto, Koji</creatorcontrib><creatorcontrib>Yasui, Hiroyuki</creatorcontrib><creatorcontrib>Taniguchi, Takashi</creatorcontrib><creatorcontrib>Shimohama, Shun</creatorcontrib><title>Synergistic effect of galantamine on nicotine-induced neuroprotection in hemiparkinsonian rat model</title><title>Neuroscience research</title><addtitle>Neurosci Res</addtitle><description>Recent studies have reported that smokers tend to be less susceptible to Parkinson’s disease (PD) and the stimulation of nicotinic acetylcholine receptor (nAChR) is considered to confer a neuroprotective effect. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiating ligand for nAChRs. However, the effects of galantamine and nicotine on dopaminergic neurons remain unclear. This study evaluated the neuroprotective effects of galantamine and nicotine in a rat 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian model. 6-OHDA with or without galantamine and/or nicotine were injected into unilateral substantia nigra of rats. Although methamphetamine-stimulated rotational behavior and dopaminergic neuronal loss induced by 6-OHDA were not inhibited by galantamine alone, those were moderately inhibited by nicotine alone. In addition, 6-OHDA-induced neuronal loss and rotational behavior were synergistically inhibited by co-injection of galantamine and nicotine. These protective effects were abolished by mecamylamine, an nAChR antagonist. We further found that α7 nAChR was expressed on both tyrosine hydroxylase (TH)-immunopositive and TH-immunonegative neurons in the SNpc. A combination of galantamine and nicotine greatly suppressed 6-OHDA-induced reduction of TH-immunopositive/α7 nAChR-immunopositive neurons. These results suggest that galantamine synergistically enhances the neuroprotective effect of nicotine against 6-OHDA-induced dopaminergic neuronal loss through an allosteric modulation of α7 nAChR activation.</description><subject>6-Hydroxydopamine</subject><subject>Allosteric potentiating ligand</subject><subject>alpha7 Nicotinic Acetylcholine Receptor</subject><subject>Animals</subject><subject>Disease Models, Animal</subject><subject>Dopamine Uptake Inhibitors - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Synergism</subject><subject>Electron Spin Resonance Spectroscopy - methods</subject><subject>Functional Laterality</subject><subject>Galantamine</subject><subject>Galantamine - therapeutic use</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Male</subject><subject>Mecamylamine - pharmacology</subject><subject>Methamphetamine - pharmacology</subject><subject>Motor Activity - drug effects</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Nicotine - therapeutic use</subject><subject>Nicotinic acetylcholine receptor</subject><subject>Nicotinic Antagonists - pharmacology</subject><subject>Parkinsonian Disorders - drug therapy</subject><subject>Parkinsonian Disorders - etiology</subject><subject>Parkinsonian Disorders - metabolism</subject><subject>Parkinson’s disease</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Nicotinic - genetics</subject><subject>Receptors, Nicotinic - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Rotarod Performance Test</subject><subject>Tyrosine 3-Monooxygenase - metabolism</subject><issn>0168-0102</issn><issn>1872-8111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1r3DAQhkVpaDYf_6AUnXqzI9mSLV0CJSRNIJBD2rPQjkaptmtpI9mB_Pto2YXeepo5PO98PIR85azljA9XmzbikrG0HWOqZbplrP9EVlyNXaM455_JqmKqYZx1p-SslA2rhBb9F3LKlRKSa7Ei8PweMb-EMgeg6D3CTJOnL3Zr42ynEJGmSGOANNe-CdEtgI7uV6ddTnPlQwVCpH9wCjub_4ZYUgw20mxnOiWH2wty4u224OWxnpPfd7e_bu6bx6efDzc_HhsQis8NyF5LUEIxGJQUg9NajIr10DkcpQfo1tbLbnAg0XZrD95rGHEYe752snf9Ofl-mFsPe12wzGYKBXBbX8G0FMN1L6RWQwXFAYScSsnozS6HyeZ3w5nZyzUbc5Br9nIN06aqq7Fvx_nLekL3L3S0WYHrA4D1y7eA2RQIGKuwkKso41L4_4YPakyP-g</recordid><startdate>20081201</startdate><enddate>20081201</enddate><creator>Yanagida, Takashi</creator><creator>Takeuchi, Hiroki</creator><creator>Kitamura, Yoshihisa</creator><creator>Takata, Kazuyuki</creator><creator>Minamino, Hideaki</creator><creator>Shibaike, Tomonori</creator><creator>Tsushima, Jun</creator><creator>Kishimoto, Koji</creator><creator>Yasui, Hiroyuki</creator><creator>Taniguchi, Takashi</creator><creator>Shimohama, Shun</creator><general>Elsevier Ireland Ltd</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>7TK</scope></search><sort><creationdate>20081201</creationdate><title>Synergistic effect of galantamine on nicotine-induced neuroprotection in hemiparkinsonian rat model</title><author>Yanagida, Takashi ; Takeuchi, Hiroki ; Kitamura, Yoshihisa ; Takata, Kazuyuki ; Minamino, Hideaki ; Shibaike, Tomonori ; Tsushima, Jun ; Kishimoto, Koji ; Yasui, Hiroyuki ; Taniguchi, Takashi ; Shimohama, Shun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-c5395c8480c68546d9947803c2de75fcc2baf526dc5ea2bfcff9c7e6731bd53d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>6-Hydroxydopamine</topic><topic>Allosteric potentiating ligand</topic><topic>alpha7 Nicotinic Acetylcholine Receptor</topic><topic>Animals</topic><topic>Disease Models, Animal</topic><topic>Dopamine Uptake Inhibitors - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Synergism</topic><topic>Electron Spin Resonance Spectroscopy - methods</topic><topic>Functional Laterality</topic><topic>Galantamine</topic><topic>Galantamine - therapeutic use</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Male</topic><topic>Mecamylamine - pharmacology</topic><topic>Methamphetamine - pharmacology</topic><topic>Motor Activity - drug effects</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Nicotine - therapeutic use</topic><topic>Nicotinic acetylcholine receptor</topic><topic>Nicotinic Antagonists - pharmacology</topic><topic>Parkinsonian Disorders - drug therapy</topic><topic>Parkinsonian Disorders - etiology</topic><topic>Parkinsonian Disorders - metabolism</topic><topic>Parkinson’s disease</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Nicotinic - genetics</topic><topic>Receptors, Nicotinic - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Rotarod Performance Test</topic><topic>Tyrosine 3-Monooxygenase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yanagida, Takashi</creatorcontrib><creatorcontrib>Takeuchi, Hiroki</creatorcontrib><creatorcontrib>Kitamura, Yoshihisa</creatorcontrib><creatorcontrib>Takata, Kazuyuki</creatorcontrib><creatorcontrib>Minamino, Hideaki</creatorcontrib><creatorcontrib>Shibaike, Tomonori</creatorcontrib><creatorcontrib>Tsushima, Jun</creatorcontrib><creatorcontrib>Kishimoto, Koji</creatorcontrib><creatorcontrib>Yasui, Hiroyuki</creatorcontrib><creatorcontrib>Taniguchi, Takashi</creatorcontrib><creatorcontrib>Shimohama, Shun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Neuroscience research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yanagida, Takashi</au><au>Takeuchi, Hiroki</au><au>Kitamura, Yoshihisa</au><au>Takata, Kazuyuki</au><au>Minamino, Hideaki</au><au>Shibaike, Tomonori</au><au>Tsushima, Jun</au><au>Kishimoto, Koji</au><au>Yasui, Hiroyuki</au><au>Taniguchi, Takashi</au><au>Shimohama, Shun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic effect of galantamine on nicotine-induced neuroprotection in hemiparkinsonian rat model</atitle><jtitle>Neuroscience research</jtitle><addtitle>Neurosci Res</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>62</volume><issue>4</issue><spage>254</spage><epage>261</epage><pages>254-261</pages><issn>0168-0102</issn><eissn>1872-8111</eissn><abstract>Recent studies have reported that smokers tend to be less susceptible to Parkinson’s disease (PD) and the stimulation of nicotinic acetylcholine receptor (nAChR) is considered to confer a neuroprotective effect. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiating ligand for nAChRs. However, the effects of galantamine and nicotine on dopaminergic neurons remain unclear. This study evaluated the neuroprotective effects of galantamine and nicotine in a rat 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian model. 6-OHDA with or without galantamine and/or nicotine were injected into unilateral substantia nigra of rats. Although methamphetamine-stimulated rotational behavior and dopaminergic neuronal loss induced by 6-OHDA were not inhibited by galantamine alone, those were moderately inhibited by nicotine alone. In addition, 6-OHDA-induced neuronal loss and rotational behavior were synergistically inhibited by co-injection of galantamine and nicotine. These protective effects were abolished by mecamylamine, an nAChR antagonist. We further found that α7 nAChR was expressed on both tyrosine hydroxylase (TH)-immunopositive and TH-immunonegative neurons in the SNpc. A combination of galantamine and nicotine greatly suppressed 6-OHDA-induced reduction of TH-immunopositive/α7 nAChR-immunopositive neurons. These results suggest that galantamine synergistically enhances the neuroprotective effect of nicotine against 6-OHDA-induced dopaminergic neuronal loss through an allosteric modulation of α7 nAChR activation.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>18845194</pmid><doi>10.1016/j.neures.2008.09.003</doi><tpages>8</tpages></addata></record> |
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| subjects | 6-Hydroxydopamine Allosteric potentiating ligand alpha7 Nicotinic Acetylcholine Receptor Animals Disease Models, Animal Dopamine Uptake Inhibitors - pharmacology Dose-Response Relationship, Drug Drug Synergism Electron Spin Resonance Spectroscopy - methods Functional Laterality Galantamine Galantamine - therapeutic use Gene Expression Regulation - drug effects Male Mecamylamine - pharmacology Methamphetamine - pharmacology Motor Activity - drug effects Neuroprotective Agents - therapeutic use Nicotine - therapeutic use Nicotinic acetylcholine receptor Nicotinic Antagonists - pharmacology Parkinsonian Disorders - drug therapy Parkinsonian Disorders - etiology Parkinsonian Disorders - metabolism Parkinson’s disease Rats Rats, Wistar Receptors, Nicotinic - genetics Receptors, Nicotinic - metabolism RNA, Messenger - metabolism Rotarod Performance Test Tyrosine 3-Monooxygenase - metabolism |
| title | Synergistic effect of galantamine on nicotine-induced neuroprotection in hemiparkinsonian rat model |
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