Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease
Abstract MicroRNAs (miRNAs) are found in nerve terminals, synaptic vesicles, and synaptosomes, but it is unclear whether synaptic and cytosolic miRNA populations differ in Alzheimer’s disease (AD) or if synaptosomal miRNAs affect AD synapse activity. To address these questions, we generated synaptos...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-08-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-022-00319-8 |
| _version_ | 1818499019418107904 |
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| author | Subodh Kumar Erika Orlov Prashanth Gowda Chhanda Bose Russell H. Swerdlow Debomoy K. Lahiri P. Hemachandra Reddy |
| author_facet | Subodh Kumar Erika Orlov Prashanth Gowda Chhanda Bose Russell H. Swerdlow Debomoy K. Lahiri P. Hemachandra Reddy |
| author_sort | Subodh Kumar |
| collection | DOAJ |
| description | Abstract MicroRNAs (miRNAs) are found in nerve terminals, synaptic vesicles, and synaptosomes, but it is unclear whether synaptic and cytosolic miRNA populations differ in Alzheimer’s disease (AD) or if synaptosomal miRNAs affect AD synapse activity. To address these questions, we generated synaptosomes and cytosolic fractions from postmortem brains of AD and unaffected control (UC) samples and analyzed them using a global Affymetrix miRNAs microarray platform. A group of miRNAs significantly differed (P < 0.0001) with high fold changes variance (+/− >200-fold) in their expressions in different comparisons: (1) UC synaptosome vs UC cytosol, (2) AD synaptosomes vs AD cytosol, (3) AD cytosol vs UC cytosol, and (4) AD synaptosomes vs UC synaptosomes. MiRNAs data analysis revealed that some potential miRNAs were consistently different across sample groups. These differentially expressed miRNAs were further validated using AD postmortem brains, brains of APP transgenic (Tg2576), Tau transgenic (P301L), and wild-type mice. The miR-501-3p, miR-502-3p, and miR-877-5p were identified as potential synaptosomal miRNAs upregulated with disease progression based on AD Braak stages. Gene Ontology Enrichment and Ingenuity Pathway Analysis of synaptosomal miRNAs showed the involvement of miRNAs in nervous system development, cell junction organization, synapse assembly formation, and function of GABAergic synapse. This is the first description of synaptic versus cytosolic miRNAs in AD and their significance in synapse function. |
| first_indexed | 2024-12-10T20:23:25Z |
| format | Article |
| id | doaj.art-0c9fb0aa125c47749b7ae833c00a229c |
| institution | Directory Open Access Journal |
| issn | 2056-7944 |
| language | English |
| last_indexed | 2024-12-10T20:23:25Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj.art-0c9fb0aa125c47749b7ae833c00a229c2022-12-22T01:34:56ZengNature Portfolionpj Genomic Medicine2056-79442022-08-017111510.1038/s41525-022-00319-8Synaptosome microRNAs regulate synapse functions in Alzheimer’s diseaseSubodh Kumar0Erika Orlov1Prashanth Gowda2Chhanda Bose3Russell H. Swerdlow4Debomoy K. Lahiri5P. Hemachandra Reddy6Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences CenterInternal Medicine Department, Texas Tech University Health Sciences CenterInternal Medicine Department, Texas Tech University Health Sciences CenterInternal Medicine Department, Texas Tech University Health Sciences CenterDepartment of Neurology, the University of Kansas Medical Center, University of Kansas Alzheimer’s Disease Research CenterLaboratory of Molecular Neurogenetics’ Departments of Psychiatry and Medical & Molecular Genetics, Indiana University School of Medicine’ Indiana Alzheimer’s Disease Research Center, Stark Neuroscience Research InstituteInternal Medicine Department, Texas Tech University Health Sciences CenterAbstract MicroRNAs (miRNAs) are found in nerve terminals, synaptic vesicles, and synaptosomes, but it is unclear whether synaptic and cytosolic miRNA populations differ in Alzheimer’s disease (AD) or if synaptosomal miRNAs affect AD synapse activity. To address these questions, we generated synaptosomes and cytosolic fractions from postmortem brains of AD and unaffected control (UC) samples and analyzed them using a global Affymetrix miRNAs microarray platform. A group of miRNAs significantly differed (P < 0.0001) with high fold changes variance (+/− >200-fold) in their expressions in different comparisons: (1) UC synaptosome vs UC cytosol, (2) AD synaptosomes vs AD cytosol, (3) AD cytosol vs UC cytosol, and (4) AD synaptosomes vs UC synaptosomes. MiRNAs data analysis revealed that some potential miRNAs were consistently different across sample groups. These differentially expressed miRNAs were further validated using AD postmortem brains, brains of APP transgenic (Tg2576), Tau transgenic (P301L), and wild-type mice. The miR-501-3p, miR-502-3p, and miR-877-5p were identified as potential synaptosomal miRNAs upregulated with disease progression based on AD Braak stages. Gene Ontology Enrichment and Ingenuity Pathway Analysis of synaptosomal miRNAs showed the involvement of miRNAs in nervous system development, cell junction organization, synapse assembly formation, and function of GABAergic synapse. This is the first description of synaptic versus cytosolic miRNAs in AD and their significance in synapse function.https://doi.org/10.1038/s41525-022-00319-8 |
| spellingShingle | Subodh Kumar Erika Orlov Prashanth Gowda Chhanda Bose Russell H. Swerdlow Debomoy K. Lahiri P. Hemachandra Reddy Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease npj Genomic Medicine |
| title | Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease |
| title_full | Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease |
| title_fullStr | Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease |
| title_full_unstemmed | Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease |
| title_short | Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease |
| title_sort | synaptosome micrornas regulate synapse functions in alzheimer s disease |
| url | https://doi.org/10.1038/s41525-022-00319-8 |
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