Publicação
Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageing
| Resumo: | Adenosine neuromodulation depends on a balanced activation of inhibitory A1 (A1R) and facilitatory A2A receptors (A2AR). Both A1R and A2AR modulate hippocampal glutamate release and NMDA-dependent long-term potentiation (LTP) but ageing affects the density of both A1R and A2AR. We tested the effects of selective A1R and A2AR antagonists in the modulation of synaptic transmission and plasticity in rat hippocampal slices from three age groups (young adults, 2–3 month; middle-aged adults, 6–8 months; aged, 18–20 months). The selective A2AR antagonist SCH58261 (50 nm) attenuated LTP in all age groups, with a larger effect in aged ()63 ± 7%) than in middle-aged adults ()36 ± 9%) or young adult rats ()36 ± 9%). In contrast, the selective A1R antagonist DPCPX (50 nm) increased LTP magnitude in young adult rats (+42 ± 6%), but failed to affect LTP magnitude in the other age groups. Finally, in the continuous presence of DPCPX, SCH58261 caused a significantly larger inhibition of LTP amplitude in aged ()71 ± 45%) than middle-aged ()28 ± 9%) or young rats ()11 ± 2%). Accordingly, aged rats displayed an increased expression of A2AR mRNA in the hippocampus and a higher number of glutamatergic nerve terminals equipped with A2AR in aged (67 ± 6%) compared with middle-aged (34 ± 7%) and young rats (25 ± 5%). The results show an enhanced A2AR-mediated modulation of LTP in aged rats, in accordance with the age-associated increased expression and density of A2AR in glutamatergic terminals. This age-associated gain of function of A2AR modulating synaptic plasticity may underlie the ability of A2AR antagonists to prevent memory dysfunction in aged animals. |
|---|---|
| Autores principais: | Costenla, Ana R. |
| Outros Autores: | Diógenes, Maria J.; Canas, Paula M.; Rodrigues, Ricardo J.; Nogueira, Célia; Maroco, João; Agostinho, Paula M.; Ribeiro, Joaquim A.; Cunha, Rodrigo A.; Mendonça, Alexandre de |
| Assunto: | A1 receptors A2A receptors Adenosine Ageing Hippocampus Synaptic plasticity |
| Ano: | 2011 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Ispa-Instituto Universitário |
| Idioma: | inglês |
| Origem: | Repositório do Ispa - Instituto Universitário |
| _version_ | 1866252559614738432 |
|---|---|
| author | Costenla, Ana R. |
| author2 | Diógenes, Maria J. Canas, Paula M. Rodrigues, Ricardo J. Nogueira, Célia Maroco, João Agostinho, Paula M. Ribeiro, Joaquim A. Cunha, Rodrigo A. Mendonça, Alexandre de |
| author2_role | author author author author author author author author author |
| author_facet | Costenla, Ana R. Diógenes, Maria J. Canas, Paula M. Rodrigues, Ricardo J. Nogueira, Célia Maroco, João Agostinho, Paula M. Ribeiro, Joaquim A. Cunha, Rodrigo A. Mendonça, Alexandre de |
| author_role | author |
| contributor_name_str_mv | Repositório do ISPA |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Costenla, Ana R.\"},{\"Person.name\":\"Diógenes, Maria J.\"},{\"Person.name\":\"Canas, Paula M.\"},{\"Person.name\":\"Rodrigues, Ricardo J.\"},{\"Person.name\":\"Nogueira, Célia\"},{\"Person.name\":\"Maroco, João\"},{\"Person.name\":\"Agostinho, Paula M.\"},{\"Person.name\":\"Ribeiro, Joaquim A.\"},{\"Person.name\":\"Cunha, Rodrigo A.\"},{\"Person.name\":\"Mendonça, Alexandre de\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório do ISPA |
| datacite.creators.creator.creatorName.fl_str_mv | Costenla, Ana R. Diógenes, Maria J. Canas, Paula M. Rodrigues, Ricardo J. Nogueira, Célia Maroco, João Agostinho, Paula M. Ribeiro, Joaquim A. Cunha, Rodrigo A. Mendonça, Alexandre de |
| datacite.date.Accepted.fl_str_mv | 2011-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2012-02-16T20:58:32Z |
| datacite.date.embargoed.fl_str_mv | 2012-02-16T20:58:32Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | A1 receptors A2A receptors Adenosine Ageing Hippocampus Synaptic plasticity |
| datacite.titles.title.fl_str_mv | Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageing |
| dc.contributor.none.fl_str_mv | Repositório do ISPA |
| dc.creator.none.fl_str_mv | Costenla, Ana R. Diógenes, Maria J. Canas, Paula M. Rodrigues, Ricardo J. Nogueira, Célia Maroco, João Agostinho, Paula M. Ribeiro, Joaquim A. Cunha, Rodrigo A. Mendonça, Alexandre de |
| dc.date.Accepted.fl_str_mv | 2011-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2012-02-16T20:58:32Z |
| dc.date.embargoed.fl_str_mv | 2012-02-16T20:58:32Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10400.12/1237 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Blackwell Publishing |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | A1 receptors A2A receptors Adenosine Ageing Hippocampus Synaptic plasticity |
| dc.title.fl_str_mv | Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageing |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Adenosine neuromodulation depends on a balanced activation of inhibitory A1 (A1R) and facilitatory A2A receptors (A2AR). Both A1R and A2AR modulate hippocampal glutamate release and NMDA-dependent long-term potentiation (LTP) but ageing affects the density of both A1R and A2AR. We tested the effects of selective A1R and A2AR antagonists in the modulation of synaptic transmission and plasticity in rat hippocampal slices from three age groups (young adults, 2–3 month; middle-aged adults, 6–8 months; aged, 18–20 months). The selective A2AR antagonist SCH58261 (50 nm) attenuated LTP in all age groups, with a larger effect in aged ()63 ± 7%) than in middle-aged adults ()36 ± 9%) or young adult rats ()36 ± 9%). In contrast, the selective A1R antagonist DPCPX (50 nm) increased LTP magnitude in young adult rats (+42 ± 6%), but failed to affect LTP magnitude in the other age groups. Finally, in the continuous presence of DPCPX, SCH58261 caused a significantly larger inhibition of LTP amplitude in aged ()71 ± 45%) than middle-aged ()28 ± 9%) or young rats ()11 ± 2%). Accordingly, aged rats displayed an increased expression of A2AR mRNA in the hippocampus and a higher number of glutamatergic nerve terminals equipped with A2AR in aged (67 ± 6%) compared with middle-aged (34 ± 7%) and young rats (25 ± 5%). The results show an enhanced A2AR-mediated modulation of LTP in aged rats, in accordance with the age-associated increased expression and density of A2AR in glutamatergic terminals. This age-associated gain of function of A2AR modulating synaptic plasticity may underlie the ability of A2AR antagonists to prevent memory dysfunction in aged animals. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ispa.pt/bitstreams/3944ecbb-91e8-4da2-90bd-ab44d138716d/download |
| id | ispa_bbd0334d2bb930d678af6880425eee35 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10400.12/1237 |
| instacron_str | ispa |
| institution | Ispa-Instituto Universitário |
| instname_str | Ispa-Instituto Universitário |
| language | eng |
| network_acronym_str | ispa |
| network_name_str | Repositório do Ispa - Instituto Universitário |
| oai_identifier_str | oai:repositorio.ispa.pt:10400.12/1237 |
| organization_str_mv | urn:organizationAcronym:ispa |
| person_str_mv | Costenla, Ana R. Diógenes, Maria J. Canas, Paula M. Rodrigues, Ricardo J. Nogueira, Célia Maroco, João Agostinho, Paula M. Ribeiro, Joaquim A. Cunha, Rodrigo A. Mendonça, Alexandre de |
| publishDate | 2011 |
| publisher.none.fl_str_mv | Blackwell Publishing |
| reponame_str | Repositório do Ispa - Instituto Universitário |
| repository_id_str | urn:repositoryAcronym:ispa |
| service_str_mv | urn:repositoryAcronym:ispa |
| spelling | engBlackwell PublishingporAdenosine neuromodulation depends on a balanced activation of inhibitory A1 (A1R) and facilitatory A2A receptors (A2AR). Both A1R and A2AR modulate hippocampal glutamate release and NMDA-dependent long-term potentiation (LTP) but ageing affects the density of both A1R and A2AR. We tested the effects of selective A1R and A2AR antagonists in the modulation of synaptic transmission and plasticity in rat hippocampal slices from three age groups (young adults, 2–3 month; middle-aged adults, 6–8 months; aged, 18–20 months). The selective A2AR antagonist SCH58261 (50 nm) attenuated LTP in all age groups, with a larger effect in aged ()63 ± 7%) than in middle-aged adults ()36 ± 9%) or young adult rats ()36 ± 9%). In contrast, the selective A1R antagonist DPCPX (50 nm) increased LTP magnitude in young adult rats (+42 ± 6%), but failed to affect LTP magnitude in the other age groups. Finally, in the continuous presence of DPCPX, SCH58261 caused a significantly larger inhibition of LTP amplitude in aged ()71 ± 45%) than middle-aged ()28 ± 9%) or young rats ()11 ± 2%). Accordingly, aged rats displayed an increased expression of A2AR mRNA in the hippocampus and a higher number of glutamatergic nerve terminals equipped with A2AR in aged (67 ± 6%) compared with middle-aged (34 ± 7%) and young rats (25 ± 5%). The results show an enhanced A2AR-mediated modulation of LTP in aged rats, in accordance with the age-associated increased expression and density of A2AR in glutamatergic terminals. This age-associated gain of function of A2AR modulating synaptic plasticity may underlie the ability of A2AR antagonists to prevent memory dysfunction in aged animals.application/pdfporEnhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageingCostenla, Ana R.Diógenes, Maria J.Canas, Paula M.Rodrigues, Ricardo J.Nogueira, CéliaMaroco, JoãoAgostinho, Paula M.Ribeiro, Joaquim A.Cunha, Rodrigo A.Mendonça, Alexandre deHostingInstitutionOrganizationalRepositório do ISPAe-mailmailto:repositorio@ispa.ptrepositorio@ispa.ptISSNIsPartOf1460-95682012-02-16T20:58:32Z20112011-01-01T00:00:00ZHandlehttp://hdl.handle.net/10400.12/1237http://purl.org/coar/access_right/c_abf2open accessA1 receptorsA2A receptorsAdenosineAgeingHippocampusSynaptic plasticity484794 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ispa.pt/bitstreams/3944ecbb-91e8-4da2-90bd-ab44d138716d/downloadEuropean Journal of Neuroscience1221Zurich |
| spellingShingle | Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageing Costenla, Ana R. A1 receptors A2A receptors Adenosine Ageing Hippocampus Synaptic plasticity |
| status | SINGLETON |
| subject.fl_str_mv | A1 receptors A2A receptors Adenosine Ageing Hippocampus Synaptic plasticity |
| title | Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageing |
| title_full | Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageing |
| title_fullStr | Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageing |
| title_full_unstemmed | Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageing |
| title_short | Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageing |
| title_sort | Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hippocampus upon ageing |
| topic | A1 receptors A2A receptors Adenosine Ageing Hippocampus Synaptic plasticity |
| topic_facet | A1 receptors A2A receptors Adenosine Ageing Hippocampus Synaptic plasticity |
| url | http://hdl.handle.net/10400.12/1237 |
| visible | 1 |