Neuronal Selection Based on Relative Fitness Comparison Detects and Eliminates Amyloid-β-Induced Hyperactive Neurons in Drosophila
Summary: During adult life, damaged but viable neurons can accumulate in the organism, creating increasingly heterogeneous and dysfunctional neural circuits. One intriguing example is the aberrant increased activity of cerebral networks detected in vulnerable brain regions during preclinical stages...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-09-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422030660X |
| _version_ | 1818380780441698304 |
|---|---|
| author | Dina S. Coelho Eduardo Moreno |
| author_facet | Dina S. Coelho Eduardo Moreno |
| author_sort | Dina S. Coelho |
| collection | DOAJ |
| description | Summary: During adult life, damaged but viable neurons can accumulate in the organism, creating increasingly heterogeneous and dysfunctional neural circuits. One intriguing example is the aberrant increased activity of cerebral networks detected in vulnerable brain regions during preclinical stages of Alzheimer's disease. The pathophysiological contribution of these early functional alterations to the progression of Alzheimer's disease is uncertain. We found that a unique cell selection mechanism based on relative fitness comparison between neurons is able to target and remove aberrantly active neurons generated by heterologous human amyloid-β in Drosophila. Sustained neuronal activity is sufficient to compromise neuronal fitness and upregulate the expression of the low fitness indicators FlowerLoseB and Azot in the fly. Conversely, forced silencing of neurons restores brain fitness and reduces amyloid-β-induced cell death. The manipulation of this cell selection process, which was already proved to be conserved in humans, might be a promising new avenue to treat Alzheimer's. |
| first_indexed | 2024-12-14T02:24:07Z |
| format | Article |
| id | doaj.art-e6449cde8efc4ee89915e4b2df8e8172 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-14T02:24:07Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-e6449cde8efc4ee89915e4b2df8e81722022-12-21T23:20:25ZengElsevieriScience2589-00422020-09-01239101468Neuronal Selection Based on Relative Fitness Comparison Detects and Eliminates Amyloid-β-Induced Hyperactive Neurons in DrosophilaDina S. Coelho0Eduardo Moreno1Cell Fitness Lab, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisboa, PortugalCell Fitness Lab, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisboa, Portugal; Corresponding authorSummary: During adult life, damaged but viable neurons can accumulate in the organism, creating increasingly heterogeneous and dysfunctional neural circuits. One intriguing example is the aberrant increased activity of cerebral networks detected in vulnerable brain regions during preclinical stages of Alzheimer's disease. The pathophysiological contribution of these early functional alterations to the progression of Alzheimer's disease is uncertain. We found that a unique cell selection mechanism based on relative fitness comparison between neurons is able to target and remove aberrantly active neurons generated by heterologous human amyloid-β in Drosophila. Sustained neuronal activity is sufficient to compromise neuronal fitness and upregulate the expression of the low fitness indicators FlowerLoseB and Azot in the fly. Conversely, forced silencing of neurons restores brain fitness and reduces amyloid-β-induced cell death. The manipulation of this cell selection process, which was already proved to be conserved in humans, might be a promising new avenue to treat Alzheimer's.http://www.sciencedirect.com/science/article/pii/S258900422030660XMolecular BiologyNeuroscienceCell Biology |
| spellingShingle | Dina S. Coelho Eduardo Moreno Neuronal Selection Based on Relative Fitness Comparison Detects and Eliminates Amyloid-β-Induced Hyperactive Neurons in Drosophila iScience Molecular Biology Neuroscience Cell Biology |
| title | Neuronal Selection Based on Relative Fitness Comparison Detects and Eliminates Amyloid-β-Induced Hyperactive Neurons in Drosophila |
| title_full | Neuronal Selection Based on Relative Fitness Comparison Detects and Eliminates Amyloid-β-Induced Hyperactive Neurons in Drosophila |
| title_fullStr | Neuronal Selection Based on Relative Fitness Comparison Detects and Eliminates Amyloid-β-Induced Hyperactive Neurons in Drosophila |
| title_full_unstemmed | Neuronal Selection Based on Relative Fitness Comparison Detects and Eliminates Amyloid-β-Induced Hyperactive Neurons in Drosophila |
| title_short | Neuronal Selection Based on Relative Fitness Comparison Detects and Eliminates Amyloid-β-Induced Hyperactive Neurons in Drosophila |
| title_sort | neuronal selection based on relative fitness comparison detects and eliminates amyloid β induced hyperactive neurons in drosophila |
| topic | Molecular Biology Neuroscience Cell Biology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422030660X |
| work_keys_str_mv | AT dinascoelho neuronalselectionbasedonrelativefitnesscomparisondetectsandeliminatesamyloidbinducedhyperactiveneuronsindrosophila AT eduardomoreno neuronalselectionbasedonrelativefitnesscomparisondetectsandeliminatesamyloidbinducedhyperactiveneuronsindrosophila |