Publicação
Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3
| Resumo: | Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). This leads to neurodegeneration of specific brain and spinal cord regions, resulting in a progressive loss of motor function. Despite neuronal death, non-neuronal cells, including astrocytes, are also involved in SCA3 pathogenesis. Astrogliosis is a common pathological feature in SCA3 patients and animal models of the disease. However, the contribution of astrocytes to SCA3 is not clearly defined. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant IP3R in mediating astrocyte somatic calcium signals, and genetically ablation of IP3R2 has been widely used to study astrocyte function. Here, we aimed to investigate the relevance of IP3R2 in the onset and progression of SCA3. For this, we tested whether IP3R2 depletion and the consecutive suppression of global astrocytic calcium signalling would lead to marked changes in the behavioral phenotype of a SCA3 mouse model, the CMVMJD135 transgenic line. This was achieved by crossing IP3R2 null mice with the CMVMJD135 mouse model and performing a longitudinal behavioral characterization of these mice using well-established motor-related function tests. Our results demonstrate that IP3R2 deletion in astrocytes does not modify SCA3 progression. |
|---|---|
| Autores principais: | Garcia, Daniela Raquel Cunha |
| Outros Autores: | Fernandes, Daniela Monteiro; Correia, Joana Sofia; Carvalho, Andreia Alexandra Neves; Ferreira, Ana Catarina Coutinho Vilaça; Gomes, Sónia Isabel Nunes Guerra; Viana, João Filipe Oliveira; Oliveira, João F.; Castro, Andreia Cristiana Teixeira; Maciel, P.; Silva, Sara Carina Duarte |
| Assunto: | Astrocyte Machado–Joseph disease CMVMJD135 mice IP3R2 KO mice Motor behavior Spinocerebellar ataxias IP R2 KO mice 3 |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1866877723157200896 |
|---|---|
| author | Garcia, Daniela Raquel Cunha |
| author2 | Fernandes, Daniela Monteiro Correia, Joana Sofia Carvalho, Andreia Alexandra Neves Ferreira, Ana Catarina Coutinho Vilaça Gomes, Sónia Isabel Nunes Guerra Viana, João Filipe Oliveira Oliveira, João F. Castro, Andreia Cristiana Teixeira Maciel, P. Silva, Sara Carina Duarte |
| author2_role | author author author author author author author author author author |
| author_facet | Garcia, Daniela Raquel Cunha Fernandes, Daniela Monteiro Correia, Joana Sofia Carvalho, Andreia Alexandra Neves Ferreira, Ana Catarina Coutinho Vilaça Gomes, Sónia Isabel Nunes Guerra Viana, João Filipe Oliveira Oliveira, João F. Castro, Andreia Cristiana Teixeira Maciel, P. Silva, Sara Carina Duarte |
| author_role | author |
| contributor_name_str_mv | Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Garcia, Daniela Raquel Cunha\"},{\"Person.name\":\"Fernandes, Daniela Monteiro\"},{\"Person.name\":\"Correia, Joana Sofia\"},{\"Person.name\":\"Carvalho, Andreia Alexandra Neves\"},{\"Person.name\":\"Ferreira, Ana Catarina Coutinho Vilaça\"},{\"Person.name\":\"Gomes, Sónia Isabel Nunes Guerra\"},{\"Person.name\":\"Viana, João Filipe Oliveira\"},{\"Person.name\":\"Oliveira, João F.\"},{\"Person.name\":\"Castro, Andreia Cristiana Teixeira\"},{\"Person.name\":\"Maciel, P.\"},{\"Person.name\":\"Silva, Sara Carina Duarte\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Garcia, Daniela Raquel Cunha Fernandes, Daniela Monteiro Correia, Joana Sofia Carvalho, Andreia Alexandra Neves Ferreira, Ana Catarina Coutinho Vilaça Gomes, Sónia Isabel Nunes Guerra Viana, João Filipe Oliveira Oliveira, João F. Castro, Andreia Cristiana Teixeira Maciel, P. Silva, Sara Carina Duarte |
| datacite.date.Accepted.fl_str_mv | 2023-06-25T00:00:00Z |
| datacite.date.available.fl_str_mv | 2023-10-18T09:40:53Z |
| datacite.date.embargoed.fl_str_mv | 2023-10-18T09:40:53Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Astrocyte Machado–Joseph disease CMVMJD135 mice IP3R2 KO mice Motor behavior Spinocerebellar ataxias IP R2 KO mice 3 |
| datacite.titles.title.fl_str_mv | Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3 |
| dc.contributor.none.fl_str_mv | Universidade do Minho |
| dc.creator.none.fl_str_mv | Garcia, Daniela Raquel Cunha Fernandes, Daniela Monteiro Correia, Joana Sofia Carvalho, Andreia Alexandra Neves Ferreira, Ana Catarina Coutinho Vilaça Gomes, Sónia Isabel Nunes Guerra Viana, João Filipe Oliveira Oliveira, João F. Castro, Andreia Cristiana Teixeira Maciel, P. Silva, Sara Carina Duarte |
| dc.date.Accepted.fl_str_mv | 2023-06-25T00:00:00Z |
| dc.date.available.fl_str_mv | 2023-10-18T09:40:53Z |
| dc.date.embargoed.fl_str_mv | 2023-10-18T09:40:53Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/86970 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Multidisciplinary Digital Publishing Institute (MDPI) |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.rights.rights.copyright.fl_str_mv | openAccess |
| dc.subject.none.fl_str_mv | Astrocyte Machado–Joseph disease CMVMJD135 mice IP3R2 KO mice Motor behavior Spinocerebellar ataxias IP R2 KO mice 3 |
| dc.title.fl_str_mv | Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3 |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). This leads to neurodegeneration of specific brain and spinal cord regions, resulting in a progressive loss of motor function. Despite neuronal death, non-neuronal cells, including astrocytes, are also involved in SCA3 pathogenesis. Astrogliosis is a common pathological feature in SCA3 patients and animal models of the disease. However, the contribution of astrocytes to SCA3 is not clearly defined. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant IP3R in mediating astrocyte somatic calcium signals, and genetically ablation of IP3R2 has been widely used to study astrocyte function. Here, we aimed to investigate the relevance of IP3R2 in the onset and progression of SCA3. For this, we tested whether IP3R2 depletion and the consecutive suppression of global astrocytic calcium signalling would lead to marked changes in the behavioral phenotype of a SCA3 mouse model, the CMVMJD135 transgenic line. This was achieved by crossing IP3R2 null mice with the CMVMJD135 mouse model and performing a longitudinal behavioral characterization of these mice using well-established motor-related function tests. Our results demonstrate that IP3R2 deletion in astrocytes does not modify SCA3 progression. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://prod-dspace.uminho.pt/bitstreams/c4c31df7-38d9-409c-8461-eaed703c5a69/download |
| id | rum_e492268dfd313bace60cfda59af45db6 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/86970 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/86970 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Garcia, Daniela Raquel Cunha Fernandes, Daniela Monteiro Correia, Joana Sofia Carvalho, Andreia Alexandra Neves Ferreira, Ana Catarina Coutinho Vilaça Gomes, Sónia Isabel Nunes Guerra Viana, João Filipe Oliveira Oliveira, João F. Castro, Andreia Cristiana Teixeira Maciel, P. Silva, Sara Carina Duarte |
| publishDate | 2023 |
| publisher.none.fl_str_mv | Multidisciplinary Digital Publishing Institute (MDPI) |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engMultidisciplinary Digital Publishing Institute (MDPI)porSpinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). This leads to neurodegeneration of specific brain and spinal cord regions, resulting in a progressive loss of motor function. Despite neuronal death, non-neuronal cells, including astrocytes, are also involved in SCA3 pathogenesis. Astrogliosis is a common pathological feature in SCA3 patients and animal models of the disease. However, the contribution of astrocytes to SCA3 is not clearly defined. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant IP3R in mediating astrocyte somatic calcium signals, and genetically ablation of IP3R2 has been widely used to study astrocyte function. Here, we aimed to investigate the relevance of IP3R2 in the onset and progression of SCA3. For this, we tested whether IP3R2 depletion and the consecutive suppression of global astrocytic calcium signalling would lead to marked changes in the behavioral phenotype of a SCA3 mouse model, the CMVMJD135 transgenic line. This was achieved by crossing IP3R2 null mice with the CMVMJD135 mouse model and performing a longitudinal behavioral characterization of these mice using well-established motor-related function tests. Our results demonstrate that IP3R2 deletion in astrocytes does not modify SCA3 progression.application/pdfporGenetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3Garcia, Daniela Raquel CunhaFernandes, Daniela MonteiroCorreia, Joana SofiaCarvalho, Andreia Alexandra NevesFerreira, Ana Catarina Coutinho VilaçaGomes, Sónia Isabel Nunes GuerraViana, João Filipe OliveiraOliveira, João F.Castro, Andreia Cristiana TeixeiraMaciel, P.Silva, Sara Carina DuarteHostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptISSNIsPartOf1661-6596DOIIsPartOf10.3390/ijms2413106062023-10-18T09:40:53Z2023-06-252023-07-13T14:07:31Z2023-06-25T00:00:00ZHandlehttps://hdl.handle.net/1822/86970http://purl.org/coar/access_right/c_abf2open accessAstrocyteMachado–Joseph diseaseCMVMJD135 miceIP3R2 KO miceMotor behaviorSpinocerebellar ataxiasIP R2 KO mice 33787185 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2023-06-25http://creativecommons.org/licenses/by/4.0/openAccesshttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://prod-dspace.uminho.pt/bitstreams/c4c31df7-38d9-409c-8461-eaed703c5a69/download |
| spellingShingle | Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3 Garcia, Daniela Raquel Cunha Astrocyte Machado–Joseph disease CMVMJD135 mice IP3R2 KO mice Motor behavior Spinocerebellar ataxias IP R2 KO mice 3 |
| status | SINGLETON |
| subject.fl_str_mv | Astrocyte Machado–Joseph disease CMVMJD135 mice IP3R2 KO mice Motor behavior Spinocerebellar ataxias IP R2 KO mice 3 |
| title | Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3 |
| title_full | Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3 |
| title_fullStr | Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3 |
| title_full_unstemmed | Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3 |
| title_short | Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3 |
| title_sort | Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3 |
| topic | Astrocyte Machado–Joseph disease CMVMJD135 mice IP3R2 KO mice Motor behavior Spinocerebellar ataxias IP R2 KO mice 3 |
| topic_facet | Astrocyte Machado–Joseph disease CMVMJD135 mice IP3R2 KO mice Motor behavior Spinocerebellar ataxias IP R2 KO mice 3 |
| url | https://hdl.handle.net/1822/86970 |
| visible | 1 |