Astrocyte senescence promotes glutamate toxicity in cortical neurons
| Autor: | Tal Ronnen Oron, Judith Campisi, Li Gan, Chandani Limbad, Albert R. Davalos, Fatouma Alimirah, Tara E. Tracy, Pierre-Yves Desprez |
|---|---|
| Přispěvatelé: | Iijima, Koichi M |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Macroglial Cells Aging Physiology Molecular biology Amino Acid Transport System X-AG Excitotoxicity Gene Expression Neurodegenerative medicine.disease_cause Alzheimer's Disease Biochemistry 0302 clinical medicine Sequencing techniques Glutamate homeostasis Stem Cell Research - Nonembryonic - Human Animal Cells Medicine and Health Sciences 2.1 Biological and endogenous factors Alzheimer's Disease including Alzheimer's Disease Related Dementias Cognitive decline Aetiology Cellular Senescence Neurons Neuronal Death Multidisciplinary Cell Death Neurodegeneration Glutamate receptor Brain Neurochemistry Neurodegenerative Diseases RNA sequencing Neurotransmitters 3. Good health Cell biology medicine.anatomical_structure Neurology Cell Processes Neurological Medicine Cellular Types Glutamate Astrocyte Research Article Senescence General Science & Technology 1.1 Normal biological development and functioning Science Primary Cell Culture Glutamic Acid Glial Cells Cell fate determination Biology 03 medical and health sciences Underpinning research Alzheimer Disease Mental Health and Psychiatry medicine Acquired Cognitive Impairment Genetics Humans X-Rays Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Biology and Life Sciences Cell Biology Cell Cycle Checkpoints medicine.disease Stem Cell Research Brain Disorders Research and analysis methods 030104 developmental biology Molecular biology techniques Gene Expression Regulation Astrocytes Cellular Neuroscience Nerve Degeneration Dementia Physiological Processes Organism Development 030217 neurology & neurosurgery Neuroscience Developmental Biology |
| Zdroj: | PLoS ONE, Vol 15, Iss 1, p e0227887 (2020) PLoS ONE PloS one, vol 15, iss 1 |
| ISSN: | 1932-6203 |
| Popis: | Neurodegeneration is a major age-related pathology. Cognitive decline is characteristic of patients with Alzheimer's and related dementias and cancer patients after chemo- or radio-therapies. A recently emerged driver of these and other age-related pathologies is cellular senescence, a cell fate that entails a permanent cell cycle arrest and pro-inflammatory senescence-associated secretory phenotype (SASP). Although there is a link between inflammation and neurodegenerative diseases, there are many open questions regarding how cellular senescence affects neurodegenerative pathologies. Among the various cell types in the brain, astrocytes are the most abundant. Astrocytes have proliferative capacity and are essential for neuron survival. Here, we investigated the phenotype of primary human astrocytes made senescent by X-irradiation, and identified genes encoding glutamate and potassium transporters as specifically downregulated upon senescence. This down regulation led to neuronal cell death in co-culture assays. Unbiased RNA sequencing of transcripts expressed by non-senescent and senescent astrocytes confirmed that glutamate homeostasis pathway declines upon senescence. Our results suggest a key role for cellular senescence, particularly in astrocytes, in excitotoxicity, which may lead to neurodegeneration including Alzheimer's disease and related dementias. |
| Databáze: | OpenAIRE |
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