Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease
Abstract Background Neurogenesis is significantly impaired in the brains of both human patients and experimental animal models of Alzheimer’s disease (AD). Although deep brain stimulation promotes neurogenesis, it is an invasive technique that may damage neural circuitry along the path of the electr...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13195-020-00656-9 |
| _version_ | 1818517084277047296 |
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| author | Qian Liu Yihang Jiao Weijian Yang Beiyao Gao Daniel K. Hsu Jan Nolta Michael Russell Bruce Lyeth Theodore P. Zanto Min Zhao |
| author_facet | Qian Liu Yihang Jiao Weijian Yang Beiyao Gao Daniel K. Hsu Jan Nolta Michael Russell Bruce Lyeth Theodore P. Zanto Min Zhao |
| author_sort | Qian Liu |
| collection | DOAJ |
| description | Abstract Background Neurogenesis is significantly impaired in the brains of both human patients and experimental animal models of Alzheimer’s disease (AD). Although deep brain stimulation promotes neurogenesis, it is an invasive technique that may damage neural circuitry along the path of the electrode. To circumvent this problem, we assessed whether intracranial electrical stimulation to the brain affects neurogenesis in a mouse model of Alzheimer’s disease (5xFAD). Methods and results We used Ki67, Nestin, and doublecortin (DCX) as markers and determined that neurogenesis in both the subventricular zone (SVZ) and hippocampus were significantly reduced in the brains of 4-month-old 5xFAD mice. Guided by a finite element method (FEM) computer simulation to approximately estimate current and electric field in the mouse brain, electrodes were positioned on the skull that were likely to deliver stimulation to the SVZ and hippocampus. After a 4-week program of 40-Hz intracranial alternating current stimulation (iACS), neurogenesis indicated by expression of Ki67, Nestin, and DCX in both the SVZ and hippocampus were significantly increased compared to 5xFAD mice who received sham stimulation. The magnitude of neurogenesis was close to the wild-type (WT) age-matched unmanipulated controls. Conclusion Our results suggest that iACS is a promising, less invasive technique capable of effectively stimulating the SVZ and hippocampus regions in the mouse brain. Importantly, iACS can significantly boost neurogenesis in the brain and offers a potential treatment for AD. |
| first_indexed | 2024-12-11T00:51:27Z |
| format | Article |
| id | doaj.art-902ceb77a35344bc9e9d6b977d2dbd9d |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-11T00:51:27Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-902ceb77a35344bc9e9d6b977d2dbd9d2022-12-22T01:26:37ZengBMCAlzheimer’s Research & Therapy1758-91932020-07-0112111210.1186/s13195-020-00656-9Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s diseaseQian Liu0Yihang Jiao1Weijian Yang2Beiyao Gao3Daniel K. Hsu4Jan Nolta5Michael Russell6Bruce Lyeth7Theodore P. Zanto8Min Zhao9Department of Dermatology, Institute for Regenerative Cures, University of California at Davis, School of MedicineDepartment of Electrical and Computer Engineering, University of California at DavisDepartment of Electrical and Computer Engineering, University of California at DavisDepartment of Dermatology, Institute for Regenerative Cures, University of California at Davis, School of MedicineDepartment of Dermatology, Institute for Regenerative Cures, University of California at Davis, School of MedicineStem Cell Program and Gene Therapy Center, Institute for Regenerative Cures, Department of Internal Medicine, University of California at DavisDepartment of Dermatology, Institute for Regenerative Cures, University of California at Davis, School of MedicineCenter for Neuroscience, Department of Neurological Surgery, School of Medicine, University of California at DavisNeuroscape, Department of Neurology, University of California San Francisco – Mission Bay, Sandler Neuroscience Center MC 0444Department of Dermatology, Institute for Regenerative Cures, University of California at Davis, School of MedicineAbstract Background Neurogenesis is significantly impaired in the brains of both human patients and experimental animal models of Alzheimer’s disease (AD). Although deep brain stimulation promotes neurogenesis, it is an invasive technique that may damage neural circuitry along the path of the electrode. To circumvent this problem, we assessed whether intracranial electrical stimulation to the brain affects neurogenesis in a mouse model of Alzheimer’s disease (5xFAD). Methods and results We used Ki67, Nestin, and doublecortin (DCX) as markers and determined that neurogenesis in both the subventricular zone (SVZ) and hippocampus were significantly reduced in the brains of 4-month-old 5xFAD mice. Guided by a finite element method (FEM) computer simulation to approximately estimate current and electric field in the mouse brain, electrodes were positioned on the skull that were likely to deliver stimulation to the SVZ and hippocampus. After a 4-week program of 40-Hz intracranial alternating current stimulation (iACS), neurogenesis indicated by expression of Ki67, Nestin, and DCX in both the SVZ and hippocampus were significantly increased compared to 5xFAD mice who received sham stimulation. The magnitude of neurogenesis was close to the wild-type (WT) age-matched unmanipulated controls. Conclusion Our results suggest that iACS is a promising, less invasive technique capable of effectively stimulating the SVZ and hippocampus regions in the mouse brain. Importantly, iACS can significantly boost neurogenesis in the brain and offers a potential treatment for AD.http://link.springer.com/article/10.1186/s13195-020-00656-95xFADSubventricular zone (SVZ)HippocampusKi67NestinDoublecortin (DCX) |
| spellingShingle | Qian Liu Yihang Jiao Weijian Yang Beiyao Gao Daniel K. Hsu Jan Nolta Michael Russell Bruce Lyeth Theodore P. Zanto Min Zhao Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease Alzheimer’s Research & Therapy 5xFAD Subventricular zone (SVZ) Hippocampus Ki67 Nestin Doublecortin (DCX) |
| title | Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease |
| title_full | Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease |
| title_fullStr | Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease |
| title_full_unstemmed | Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease |
| title_short | Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease |
| title_sort | intracranial alternating current stimulation facilitates neurogenesis in a mouse model of alzheimer s disease |
| topic | 5xFAD Subventricular zone (SVZ) Hippocampus Ki67 Nestin Doublecortin (DCX) |
| url | http://link.springer.com/article/10.1186/s13195-020-00656-9 |
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