Transcriptomic Analysis in the Hippocampus and Retina of Tg2576 AD Mice Reveals Defective Mitochondrial Oxidative Phosphorylation and Recovery by Tau 12A12mAb Treatment
Increasing evidence implicates decreased energy metabolism and mitochondrial dysfunctions among the earliest pathogenic events of Alzheimer’s disease (AD). However, the molecular mechanisms underlying bioenergetic dysfunctions in AD remain, to date, largely unknown. In this work, we analyzed transcr...
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MDPI AG
2023-09-01
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| author | Giovanna Morello Maria Guarnaccia Valentina La Cognata Valentina Latina Pietro Calissano Giuseppina Amadoro Sebastiano Cavallaro |
| author_facet | Giovanna Morello Maria Guarnaccia Valentina La Cognata Valentina Latina Pietro Calissano Giuseppina Amadoro Sebastiano Cavallaro |
| author_sort | Giovanna Morello |
| collection | DOAJ |
| description | Increasing evidence implicates decreased energy metabolism and mitochondrial dysfunctions among the earliest pathogenic events of Alzheimer’s disease (AD). However, the molecular mechanisms underlying bioenergetic dysfunctions in AD remain, to date, largely unknown. In this work, we analyzed transcriptomic changes occurring in the hippocampus and retina of a Tg2576 AD mouse model and wild-type controls, evaluating their functional implications by gene set enrichment analysis. The results revealed that oxidative phosphorylation and mitochondrial-related pathways are significantly down-regulated in both tissues of Tg2576 mice, supporting the role of these processes in the pathogenesis of AD. In addition, we also analyzed transcriptomic changes occurring in Tg2576 mice treated with the 12A12 monoclonal antibody that neutralizes an AD-relevant tau-derived neurotoxic peptide <i>in vivo</i>. Our analysis showed that the mitochondrial alterations observed in AD mice were significantly reverted by treatment with 12A12mAb, supporting bioenergetic pathways as key mediators of its <i>in vivo</i> neuroprotective and anti-amyloidogenic effects. This study provides, for the first time, a comprehensive characterization of molecular events underlying the disrupted mitochondrial bioenergetics in AD pathology, laying the foundation for the future development of diagnostic and therapeutic tools. |
| first_indexed | 2024-03-10T22:56:05Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T22:56:05Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-358f217c82594c0390666379dbfcf1f32023-11-19T09:59:28ZengMDPI AGCells2073-44092023-09-011218225410.3390/cells12182254Transcriptomic Analysis in the Hippocampus and Retina of Tg2576 AD Mice Reveals Defective Mitochondrial Oxidative Phosphorylation and Recovery by Tau 12A12mAb TreatmentGiovanna Morello0Maria Guarnaccia1Valentina La Cognata2Valentina Latina3Pietro Calissano4Giuseppina Amadoro5Sebastiano Cavallaro6Institute for Biomedical Research and Innovation, National Research Council (CNR-IRIB), Via Paolo Gaifami, 18, 95126 Catania, ItalyInstitute for Biomedical Research and Innovation, National Research Council (CNR-IRIB), Via Paolo Gaifami, 18, 95126 Catania, ItalyInstitute for Biomedical Research and Innovation, National Research Council (CNR-IRIB), Via Paolo Gaifami, 18, 95126 Catania, ItalyEuropean Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, ItalyEuropean Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, ItalyEuropean Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, ItalyInstitute for Biomedical Research and Innovation, National Research Council (CNR-IRIB), Via Paolo Gaifami, 18, 95126 Catania, ItalyIncreasing evidence implicates decreased energy metabolism and mitochondrial dysfunctions among the earliest pathogenic events of Alzheimer’s disease (AD). However, the molecular mechanisms underlying bioenergetic dysfunctions in AD remain, to date, largely unknown. In this work, we analyzed transcriptomic changes occurring in the hippocampus and retina of a Tg2576 AD mouse model and wild-type controls, evaluating their functional implications by gene set enrichment analysis. The results revealed that oxidative phosphorylation and mitochondrial-related pathways are significantly down-regulated in both tissues of Tg2576 mice, supporting the role of these processes in the pathogenesis of AD. In addition, we also analyzed transcriptomic changes occurring in Tg2576 mice treated with the 12A12 monoclonal antibody that neutralizes an AD-relevant tau-derived neurotoxic peptide <i>in vivo</i>. Our analysis showed that the mitochondrial alterations observed in AD mice were significantly reverted by treatment with 12A12mAb, supporting bioenergetic pathways as key mediators of its <i>in vivo</i> neuroprotective and anti-amyloidogenic effects. This study provides, for the first time, a comprehensive characterization of molecular events underlying the disrupted mitochondrial bioenergetics in AD pathology, laying the foundation for the future development of diagnostic and therapeutic tools.https://www.mdpi.com/2073-4409/12/18/2254transcriptomicRNA-seqGSEAsystems biologytau immunotherapyTg2576 |
| spellingShingle | Giovanna Morello Maria Guarnaccia Valentina La Cognata Valentina Latina Pietro Calissano Giuseppina Amadoro Sebastiano Cavallaro Transcriptomic Analysis in the Hippocampus and Retina of Tg2576 AD Mice Reveals Defective Mitochondrial Oxidative Phosphorylation and Recovery by Tau 12A12mAb Treatment Cells transcriptomic RNA-seq GSEA systems biology tau immunotherapy Tg2576 |
| title | Transcriptomic Analysis in the Hippocampus and Retina of Tg2576 AD Mice Reveals Defective Mitochondrial Oxidative Phosphorylation and Recovery by Tau 12A12mAb Treatment |
| title_full | Transcriptomic Analysis in the Hippocampus and Retina of Tg2576 AD Mice Reveals Defective Mitochondrial Oxidative Phosphorylation and Recovery by Tau 12A12mAb Treatment |
| title_fullStr | Transcriptomic Analysis in the Hippocampus and Retina of Tg2576 AD Mice Reveals Defective Mitochondrial Oxidative Phosphorylation and Recovery by Tau 12A12mAb Treatment |
| title_full_unstemmed | Transcriptomic Analysis in the Hippocampus and Retina of Tg2576 AD Mice Reveals Defective Mitochondrial Oxidative Phosphorylation and Recovery by Tau 12A12mAb Treatment |
| title_short | Transcriptomic Analysis in the Hippocampus and Retina of Tg2576 AD Mice Reveals Defective Mitochondrial Oxidative Phosphorylation and Recovery by Tau 12A12mAb Treatment |
| title_sort | transcriptomic analysis in the hippocampus and retina of tg2576 ad mice reveals defective mitochondrial oxidative phosphorylation and recovery by tau 12a12mab treatment |
| topic | transcriptomic RNA-seq GSEA systems biology tau immunotherapy Tg2576 |
| url | https://www.mdpi.com/2073-4409/12/18/2254 |
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