Astrocyte dystrophy in ageing brain parallels impaired synaptic plasticity
| Autor: | Alexey R. Brazhe, Andrey Popov, Oksana Sutyagina, Alexey Semyanov, Alexei Verkhratsky, Natalia Lazareva, Pavel Denisov, Li Li |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Aging Long-Term Potentiation Longevity Glutamic Acid Hippocampal formation Biology Hippocampus 03 medical and health sciences 0302 clinical medicine astrocyte medicine glutamate uptake Animals astrocytic complexity Patch clamp Cognitive decline Cell Size astrocytic cradle Original Paper Neuronal Plasticity Cell Membrane Glutamate receptor Long-term potentiation Cell Biology Original Articles K+ buffering medicine.disease Astrogliosis Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure perisynaptic astrocytic processes ageing Astrocytes Synaptic plasticity Potassium Calcium Neuroscience 030217 neurology & neurosurgery Astrocyte |
| Zdroj: | Addi. Archivo Digital para la Docencia y la Investigación instname Aging Cell Addi: Archivo Digital para la Docencia y la Investigación Universidad del País Vasco |
| Popis: | Little is known about age‐dependent changes in structure and function of astrocytes and of the impact of these on the cognitive decline in the senescent brain. The prevalent view on the age‐dependent increase in reactive astrogliosis and astrocytic hypertrophy requires scrutiny and detailed analysis. Using two‐photon microscopy in conjunction with 3D reconstruction, Sholl and volume fraction analysis, we demonstrate a significant reduction in the number and the length of astrocytic processes, in astrocytic territorial domains and in astrocyte‐to‐astrocyte coupling in the aged brain. Probing physiology of astrocytes with patch clamp, and Ca2+ imaging revealed deficits in K+ and glutamate clearance and spatiotemporal reorganisation of Ca2+ events in old astrocytes. These changes paralleled impaired synaptic long‐term potentiation (LTP) in hippocampal CA1 in old mice. Our findings may explain the astroglial mechanisms of age‐dependent decline in learning and memory. Ageing reduces the number and the length of astrocytic processes, astrocytic territorial domains and astrocyte‐to‐astrocyte coupling in the hippocampus. Such dystrophy causes deficits in K+ and glutamate clearance by astrocytes. Enhanced glutamate spillover impairs synaptic long‐term potentiation (LTP) in hippocampal CA1, which may represent the astroglial mechanisms of age‐dependent decline in learning and memory. |
| Databáze: | OpenAIRE |
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