Normal aging in rats and pathological aging in human Alzheimer’s disease decrease FAAH activity: Modulation by cannabinoid agonists
Anandamide is an endocannabinoid involved in several physiological functions including neuroprotection. Anandamide is synthesized on demand and its endogenous level is regulated through its degradation, where fatty acid amide hydrolase plays a major role. The aim of this study was to characterize an...
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| Veröffentlicht in: | Experimental gerontology 2014-12, Vol.60, p.92-99 |
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| creator | Pascual, A.C. Martín-Moreno, A.M. Giusto, N.M. de Ceballos, M.L. Pasquaré, S.J. |
| description | Anandamide is an endocannabinoid involved in several physiological functions including neuroprotection. Anandamide is synthesized on demand and its endogenous level is regulated through its degradation, where fatty acid amide hydrolase plays a major role. The aim of this study was to characterize anandamide breakdown in physiological and pathological aging and its regulation by CB1 and CB2 receptor agonists.
Fatty acid amide hydrolase activity was analyzed in an independent cohort of human cortical membrane samples from control and Alzheimer’s disease patients, and in membrane and synaptosomes from adult and aged rat cerebral cortex. Our results demonstrate that fatty acid amide hydrolase activity decreases in the frontal cortex from human patients with Alzheimer’s disease and this effect is mimicked by Aβ1-40 peptide. This activity increases and decreases in aged rat cerebrocortical membranes and synaptosomes, respectively. Also, while the presence of JWH-133, a CB2 selective agonist, slightly increases anandamide hydrolysis in human controls, it decreases this activity in adults and aged rat cerebrocortical membranes and synaptosomes. In the presence of WIN55,212-2, a mixed CB1/CB2 agonist, anandamide hydrolysis increases in Alzheimer’s disease patients but decreases in human controls as well as in adult and aged rat cerebrocortical membranes and synaptosomes. Although a similar profile is observed in fatty acid amide hydrolase activity between aged rat synaptic endings and human Alzheimer’s disease brains, it is differently modulated by CB1/CB2 agonists. This modulation leads to a reduced availability of anandamide in Alzheimer’s disease and to an increased availability of this endocannabinoid in aging.
•FAAH activity presents a similar profile in aged synaptic endings and AD brains.•FAAH activity is differently modulated by CB1/CB2 agonists.•FAAH activity is reduced in AD and increased in aging by CBR agonists. |
| doi_str_mv | 10.1016/j.exger.2014.10.011 |
| format | Article |
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Fatty acid amide hydrolase activity was analyzed in an independent cohort of human cortical membrane samples from control and Alzheimer’s disease patients, and in membrane and synaptosomes from adult and aged rat cerebral cortex. Our results demonstrate that fatty acid amide hydrolase activity decreases in the frontal cortex from human patients with Alzheimer’s disease and this effect is mimicked by Aβ1-40 peptide. This activity increases and decreases in aged rat cerebrocortical membranes and synaptosomes, respectively. Also, while the presence of JWH-133, a CB2 selective agonist, slightly increases anandamide hydrolysis in human controls, it decreases this activity in adults and aged rat cerebrocortical membranes and synaptosomes. In the presence of WIN55,212-2, a mixed CB1/CB2 agonist, anandamide hydrolysis increases in Alzheimer’s disease patients but decreases in human controls as well as in adult and aged rat cerebrocortical membranes and synaptosomes. Although a similar profile is observed in fatty acid amide hydrolase activity between aged rat synaptic endings and human Alzheimer’s disease brains, it is differently modulated by CB1/CB2 agonists. This modulation leads to a reduced availability of anandamide in Alzheimer’s disease and to an increased availability of this endocannabinoid in aging.
•FAAH activity presents a similar profile in aged synaptic endings and AD brains.•FAAH activity is differently modulated by CB1/CB2 agonists.•FAAH activity is reduced in AD and increased in aging by CBR agonists.</description><identifier>ISSN: 0531-5565</identifier><identifier>EISSN: 1873-6815</identifier><identifier>DOI: 10.1016/j.exger.2014.10.011</identifier><identifier>PMID: 25456842</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Aged ; Aged, 80 and over ; Aging ; Aging - metabolism ; Alzheimer Disease - drug therapy ; Alzheimer Disease - metabolism ; Alzheimer's disease ; Amidohydrolases - antagonists & inhibitors ; Amidohydrolases - metabolism ; Amyloid beta-Peptides - metabolism ; Anandamide ; Animals ; Arachidonic Acids - metabolism ; Benzamides - pharmacology ; Benzoxazines - pharmacology ; Cannabinoid Receptor Agonists - pharmacology ; Cannabinoid receptors ; Cannabinoids - pharmacology ; Carbamates - pharmacology ; Case-Control Studies ; Central nervous system ; Cerebral Cortex - drug effects ; Cerebral Cortex - metabolism ; Endocannabinoids - metabolism ; Enzyme Inhibitors - pharmacology ; Fatty acid amide hydrolase ; Female ; Frontal Lobe - drug effects ; Frontal Lobe - metabolism ; Humans ; In Vitro Techniques ; Male ; Middle Aged ; Morpholines - pharmacology ; Naphthalenes - pharmacology ; Polyunsaturated Alkamides - metabolism ; Rats ; Rats, Wistar ; Synaptosomes - drug effects ; Synaptosomes - metabolism</subject><ispartof>Experimental gerontology, 2014-12, Vol.60, p.92-99</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c458t-77e0159a587348c6c77d2cb35b6755590e0135f22be3953b818ed4e4789a96b13</citedby><cites>FETCH-LOGICAL-c458t-77e0159a587348c6c77d2cb35b6755590e0135f22be3953b818ed4e4789a96b13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0531556514002903$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25456842$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pascual, A.C.</creatorcontrib><creatorcontrib>Martín-Moreno, A.M.</creatorcontrib><creatorcontrib>Giusto, N.M.</creatorcontrib><creatorcontrib>de Ceballos, M.L.</creatorcontrib><creatorcontrib>Pasquaré, S.J.</creatorcontrib><title>Normal aging in rats and pathological aging in human Alzheimer’s disease decrease FAAH activity: Modulation by cannabinoid agonists</title><title>Experimental gerontology</title><addtitle>Exp Gerontol</addtitle><description>Anandamide is an endocannabinoid involved in several physiological functions including neuroprotection. Anandamide is synthesized on demand and its endogenous level is regulated through its degradation, where fatty acid amide hydrolase plays a major role. The aim of this study was to characterize anandamide breakdown in physiological and pathological aging and its regulation by CB1 and CB2 receptor agonists.
Fatty acid amide hydrolase activity was analyzed in an independent cohort of human cortical membrane samples from control and Alzheimer’s disease patients, and in membrane and synaptosomes from adult and aged rat cerebral cortex. Our results demonstrate that fatty acid amide hydrolase activity decreases in the frontal cortex from human patients with Alzheimer’s disease and this effect is mimicked by Aβ1-40 peptide. This activity increases and decreases in aged rat cerebrocortical membranes and synaptosomes, respectively. Also, while the presence of JWH-133, a CB2 selective agonist, slightly increases anandamide hydrolysis in human controls, it decreases this activity in adults and aged rat cerebrocortical membranes and synaptosomes. In the presence of WIN55,212-2, a mixed CB1/CB2 agonist, anandamide hydrolysis increases in Alzheimer’s disease patients but decreases in human controls as well as in adult and aged rat cerebrocortical membranes and synaptosomes. Although a similar profile is observed in fatty acid amide hydrolase activity between aged rat synaptic endings and human Alzheimer’s disease brains, it is differently modulated by CB1/CB2 agonists. This modulation leads to a reduced availability of anandamide in Alzheimer’s disease and to an increased availability of this endocannabinoid in aging.
•FAAH activity presents a similar profile in aged synaptic endings and AD brains.•FAAH activity is differently modulated by CB1/CB2 agonists.•FAAH activity is reduced in AD and increased in aging by CBR agonists.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging</subject><subject>Aging - metabolism</subject><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer's disease</subject><subject>Amidohydrolases - antagonists & inhibitors</subject><subject>Amidohydrolases - metabolism</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Anandamide</subject><subject>Animals</subject><subject>Arachidonic Acids - metabolism</subject><subject>Benzamides - pharmacology</subject><subject>Benzoxazines - pharmacology</subject><subject>Cannabinoid Receptor Agonists - pharmacology</subject><subject>Cannabinoid receptors</subject><subject>Cannabinoids - pharmacology</subject><subject>Carbamates - pharmacology</subject><subject>Case-Control Studies</subject><subject>Central nervous system</subject><subject>Cerebral Cortex - drug effects</subject><subject>Cerebral Cortex - metabolism</subject><subject>Endocannabinoids - metabolism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fatty acid amide hydrolase</subject><subject>Female</subject><subject>Frontal Lobe - drug effects</subject><subject>Frontal Lobe - metabolism</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Morpholines - pharmacology</subject><subject>Naphthalenes - pharmacology</subject><subject>Polyunsaturated Alkamides - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Synaptosomes - drug effects</subject><subject>Synaptosomes - metabolism</subject><issn>0531-5565</issn><issn>1873-6815</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFuEzEQhi0EoqHwBEjIRy4b7PWO14vEIaooRWrhAmfLa08SR7t2sHcrwolLH6Kv1yfpJmkRJ8RpRjPfzK-Zn5DXnM054_LdZo4_V5jmJePVVJkzzp-QGVe1KKTi8JTMGAheAEg4IS9y3jDGZCn4c3JSQgVSVeWM3HyJqTcdNSsfVtQHmsyQqQmObs2wjl1ceft3ez32JtBF92uNvsd09_s2U-czmozUoU2H5HyxuKDGDv7aD7v39Cq6sTODj4G2O2pNCKb1IXo3rY3B5yG_JM-Wpsv46iGeku_nH7-dXRSXXz99PltcFrYCNRR1jYxDY2C6sVJW2rp2pW0FtLIGgIZNbQHLsmxRNCBaxRW6CqtaNaaRLRen5O1x7zbFHyPmQfc-W-w6EzCOWfMaBHBQ_D9QKYAxUQk1oeKI2hRzTrjU2-R7k3aaM723Sm_0wSq9t2pfZAeBNw8CY9uj-zPz6M0EfDgCOH3k2k_j2XoMFp1PaAftov-nwD1y_qbJ</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>Pascual, A.C.</creator><creator>Martín-Moreno, A.M.</creator><creator>Giusto, N.M.</creator><creator>de Ceballos, M.L.</creator><creator>Pasquaré, S.J.</creator><general>Elsevier Inc</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><scope>7TK</scope></search><sort><creationdate>20141201</creationdate><title>Normal aging in rats and pathological aging in human Alzheimer’s disease decrease FAAH activity: Modulation by cannabinoid agonists</title><author>Pascual, A.C. ; Martín-Moreno, A.M. ; Giusto, N.M. ; de Ceballos, M.L. ; Pasquaré, S.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-77e0159a587348c6c77d2cb35b6755590e0135f22be3953b818ed4e4789a96b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aging</topic><topic>Aging - metabolism</topic><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer's disease</topic><topic>Amidohydrolases - antagonists & inhibitors</topic><topic>Amidohydrolases - metabolism</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Anandamide</topic><topic>Animals</topic><topic>Arachidonic Acids - metabolism</topic><topic>Benzamides - pharmacology</topic><topic>Benzoxazines - pharmacology</topic><topic>Cannabinoid Receptor Agonists - pharmacology</topic><topic>Cannabinoid receptors</topic><topic>Cannabinoids - pharmacology</topic><topic>Carbamates - pharmacology</topic><topic>Case-Control Studies</topic><topic>Central nervous system</topic><topic>Cerebral Cortex - drug effects</topic><topic>Cerebral Cortex - metabolism</topic><topic>Endocannabinoids - metabolism</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fatty acid amide hydrolase</topic><topic>Female</topic><topic>Frontal Lobe - drug effects</topic><topic>Frontal Lobe - metabolism</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Morpholines - pharmacology</topic><topic>Naphthalenes - pharmacology</topic><topic>Polyunsaturated Alkamides - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Synaptosomes - drug effects</topic><topic>Synaptosomes - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pascual, A.C.</creatorcontrib><creatorcontrib>Martín-Moreno, A.M.</creatorcontrib><creatorcontrib>Giusto, N.M.</creatorcontrib><creatorcontrib>de Ceballos, M.L.</creatorcontrib><creatorcontrib>Pasquaré, S.J.</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><collection>Neurosciences Abstracts</collection><jtitle>Experimental gerontology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pascual, A.C.</au><au>Martín-Moreno, A.M.</au><au>Giusto, N.M.</au><au>de Ceballos, M.L.</au><au>Pasquaré, S.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Normal aging in rats and pathological aging in human Alzheimer’s disease decrease FAAH activity: Modulation by cannabinoid agonists</atitle><jtitle>Experimental gerontology</jtitle><addtitle>Exp Gerontol</addtitle><date>2014-12-01</date><risdate>2014</risdate><volume>60</volume><spage>92</spage><epage>99</epage><pages>92-99</pages><issn>0531-5565</issn><eissn>1873-6815</eissn><abstract>Anandamide is an endocannabinoid involved in several physiological functions including neuroprotection. Anandamide is synthesized on demand and its endogenous level is regulated through its degradation, where fatty acid amide hydrolase plays a major role. The aim of this study was to characterize anandamide breakdown in physiological and pathological aging and its regulation by CB1 and CB2 receptor agonists.
Fatty acid amide hydrolase activity was analyzed in an independent cohort of human cortical membrane samples from control and Alzheimer’s disease patients, and in membrane and synaptosomes from adult and aged rat cerebral cortex. Our results demonstrate that fatty acid amide hydrolase activity decreases in the frontal cortex from human patients with Alzheimer’s disease and this effect is mimicked by Aβ1-40 peptide. This activity increases and decreases in aged rat cerebrocortical membranes and synaptosomes, respectively. Also, while the presence of JWH-133, a CB2 selective agonist, slightly increases anandamide hydrolysis in human controls, it decreases this activity in adults and aged rat cerebrocortical membranes and synaptosomes. In the presence of WIN55,212-2, a mixed CB1/CB2 agonist, anandamide hydrolysis increases in Alzheimer’s disease patients but decreases in human controls as well as in adult and aged rat cerebrocortical membranes and synaptosomes. Although a similar profile is observed in fatty acid amide hydrolase activity between aged rat synaptic endings and human Alzheimer’s disease brains, it is differently modulated by CB1/CB2 agonists. This modulation leads to a reduced availability of anandamide in Alzheimer’s disease and to an increased availability of this endocannabinoid in aging.
•FAAH activity presents a similar profile in aged synaptic endings and AD brains.•FAAH activity is differently modulated by CB1/CB2 agonists.•FAAH activity is reduced in AD and increased in aging by CBR agonists.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>25456842</pmid><doi>10.1016/j.exger.2014.10.011</doi><tpages>8</tpages></addata></record> |
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| subjects | Aged Aged, 80 and over Aging Aging - metabolism Alzheimer Disease - drug therapy Alzheimer Disease - metabolism Alzheimer's disease Amidohydrolases - antagonists & inhibitors Amidohydrolases - metabolism Amyloid beta-Peptides - metabolism Anandamide Animals Arachidonic Acids - metabolism Benzamides - pharmacology Benzoxazines - pharmacology Cannabinoid Receptor Agonists - pharmacology Cannabinoid receptors Cannabinoids - pharmacology Carbamates - pharmacology Case-Control Studies Central nervous system Cerebral Cortex - drug effects Cerebral Cortex - metabolism Endocannabinoids - metabolism Enzyme Inhibitors - pharmacology Fatty acid amide hydrolase Female Frontal Lobe - drug effects Frontal Lobe - metabolism Humans In Vitro Techniques Male Middle Aged Morpholines - pharmacology Naphthalenes - pharmacology Polyunsaturated Alkamides - metabolism Rats Rats, Wistar Synaptosomes - drug effects Synaptosomes - metabolism |
| title | Normal aging in rats and pathological aging in human Alzheimer’s disease decrease FAAH activity: Modulation by cannabinoid agonists |
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