Influence of sex, age and diabetes on brain transcriptome and proteome modifications following cerebral ischemia
Abstract Ischemic stroke is a major cause of death and disability worldwide. Translation into the clinical setting of neuroprotective agents showing promising results in pre-clinical studies has systematically failed. One possible explanation is that the animal models used to test neuroprotectants d...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-01-01
|
| Series: | BMC Neuroscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12868-023-00775-7 |
| _version_ | 1811175994362429440 |
|---|---|
| author | Laura Ramiro Júlia Faura Alba Simats Paula García-Rodríguez Feifei Ma Luna Martín Francesc Canals Anna Rosell Joan Montaner |
| author_facet | Laura Ramiro Júlia Faura Alba Simats Paula García-Rodríguez Feifei Ma Luna Martín Francesc Canals Anna Rosell Joan Montaner |
| author_sort | Laura Ramiro |
| collection | DOAJ |
| description | Abstract Ischemic stroke is a major cause of death and disability worldwide. Translation into the clinical setting of neuroprotective agents showing promising results in pre-clinical studies has systematically failed. One possible explanation is that the animal models used to test neuroprotectants do not properly represent the population affected by stroke, as most of the pre-clinical studies are performed in healthy young male mice. Therefore, we aimed to determine if the response to cerebral ischemia differed depending on age, sex and the presence of comorbidities. Thus, we explored proteomic and transcriptomic changes triggered during the hyperacute phase of cerebral ischemia (by transient intraluminal middle cerebral artery occlusion) in the brain of: (1) young male mice, (2) young female mice, (3) aged male mice and (4) diabetic young male mice. Moreover, we compared each group's proteomic and transcriptomic changes using an integrative enrichment pathways analysis to disclose key common and exclusive altered proteins, genes and pathways in the first stages of the disease. We found 61 differentially expressed genes (DEG) in male mice, 77 in females, 699 in diabetics and 24 in aged mice. Of these, only 14 were commonly dysregulated in all groups. The enrichment pathways analysis revealed that the inflammatory response was the biological process with more DEG in all groups, followed by hemopoiesis. Our findings indicate that the response to cerebral ischemia regarding proteomic and transcriptomic changes differs depending on sex, age and comorbidities, highlighting the importance of incorporating animals with different phenotypes in future stroke research studies. |
| first_indexed | 2024-04-10T19:45:49Z |
| format | Article |
| id | doaj.art-f034745269f04a3195c5e741c91af626 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-04-10T19:45:49Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-f034745269f04a3195c5e741c91af6262023-01-29T12:05:15ZengBMCBMC Neuroscience1471-22022023-01-0124111510.1186/s12868-023-00775-7Influence of sex, age and diabetes on brain transcriptome and proteome modifications following cerebral ischemiaLaura Ramiro0Júlia Faura1Alba Simats2Paula García-Rodríguez3Feifei Ma4Luna Martín5Francesc Canals6Anna Rosell7Joan Montaner8Neurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Universitat Autònoma de BarcelonaNeurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Universitat Autònoma de BarcelonaNeurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Universitat Autònoma de BarcelonaNeurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Universitat Autònoma de BarcelonaNeurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Universitat Autònoma de BarcelonaProteomics Laboratory, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autònoma de BarcelonaProteomics Laboratory, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autònoma de BarcelonaNeurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Universitat Autònoma de BarcelonaNeurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Universitat Autònoma de BarcelonaAbstract Ischemic stroke is a major cause of death and disability worldwide. Translation into the clinical setting of neuroprotective agents showing promising results in pre-clinical studies has systematically failed. One possible explanation is that the animal models used to test neuroprotectants do not properly represent the population affected by stroke, as most of the pre-clinical studies are performed in healthy young male mice. Therefore, we aimed to determine if the response to cerebral ischemia differed depending on age, sex and the presence of comorbidities. Thus, we explored proteomic and transcriptomic changes triggered during the hyperacute phase of cerebral ischemia (by transient intraluminal middle cerebral artery occlusion) in the brain of: (1) young male mice, (2) young female mice, (3) aged male mice and (4) diabetic young male mice. Moreover, we compared each group's proteomic and transcriptomic changes using an integrative enrichment pathways analysis to disclose key common and exclusive altered proteins, genes and pathways in the first stages of the disease. We found 61 differentially expressed genes (DEG) in male mice, 77 in females, 699 in diabetics and 24 in aged mice. Of these, only 14 were commonly dysregulated in all groups. The enrichment pathways analysis revealed that the inflammatory response was the biological process with more DEG in all groups, followed by hemopoiesis. Our findings indicate that the response to cerebral ischemia regarding proteomic and transcriptomic changes differs depending on sex, age and comorbidities, highlighting the importance of incorporating animals with different phenotypes in future stroke research studies.https://doi.org/10.1186/s12868-023-00775-7Ischemic strokeProteomeTranscriptomeSexDiabetesAge |
| spellingShingle | Laura Ramiro Júlia Faura Alba Simats Paula García-Rodríguez Feifei Ma Luna Martín Francesc Canals Anna Rosell Joan Montaner Influence of sex, age and diabetes on brain transcriptome and proteome modifications following cerebral ischemia BMC Neuroscience Ischemic stroke Proteome Transcriptome Sex Diabetes Age |
| title | Influence of sex, age and diabetes on brain transcriptome and proteome modifications following cerebral ischemia |
| title_full | Influence of sex, age and diabetes on brain transcriptome and proteome modifications following cerebral ischemia |
| title_fullStr | Influence of sex, age and diabetes on brain transcriptome and proteome modifications following cerebral ischemia |
| title_full_unstemmed | Influence of sex, age and diabetes on brain transcriptome and proteome modifications following cerebral ischemia |
| title_short | Influence of sex, age and diabetes on brain transcriptome and proteome modifications following cerebral ischemia |
| title_sort | influence of sex age and diabetes on brain transcriptome and proteome modifications following cerebral ischemia |
| topic | Ischemic stroke Proteome Transcriptome Sex Diabetes Age |
| url | https://doi.org/10.1186/s12868-023-00775-7 |
| work_keys_str_mv | AT lauraramiro influenceofsexageanddiabetesonbraintranscriptomeandproteomemodificationsfollowingcerebralischemia AT juliafaura influenceofsexageanddiabetesonbraintranscriptomeandproteomemodificationsfollowingcerebralischemia AT albasimats influenceofsexageanddiabetesonbraintranscriptomeandproteomemodificationsfollowingcerebralischemia AT paulagarciarodriguez influenceofsexageanddiabetesonbraintranscriptomeandproteomemodificationsfollowingcerebralischemia AT feifeima influenceofsexageanddiabetesonbraintranscriptomeandproteomemodificationsfollowingcerebralischemia AT lunamartin influenceofsexageanddiabetesonbraintranscriptomeandproteomemodificationsfollowingcerebralischemia AT francesccanals influenceofsexageanddiabetesonbraintranscriptomeandproteomemodificationsfollowingcerebralischemia AT annarosell influenceofsexageanddiabetesonbraintranscriptomeandproteomemodificationsfollowingcerebralischemia AT joanmontaner influenceofsexageanddiabetesonbraintranscriptomeandproteomemodificationsfollowingcerebralischemia |