Cannabinoid 1 receptor signaling on GABAergic neurons influences astrocytes in the ageing brain
Astrocytes, key regulators of brain homeostasis, interact with neighboring glial cells, neurons and the vasculature through complex processes involving different signaling pathways. It is not entirely clear how these interactions change in the ageing brain and which factors influence astrocyte agein...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
August 16, 2018
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| In: |
PLOS ONE
Year: 2018, Volume: 13, Issue: 8 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0202566 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1371/journal.pone.0202566 Verlag, Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202566 
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| Author Notes: | Andras Bilkei-Gorzo, Onder Albayram, Frank Ativie, Safak Chasan, Till Zimmer, Karsten Bach, Andreas Zimmer |
| Summary: | Astrocytes, key regulators of brain homeostasis, interact with neighboring glial cells, neurons and the vasculature through complex processes involving different signaling pathways. It is not entirely clear how these interactions change in the ageing brain and which factors influence astrocyte ageing. Here, we investigate the role of endocannabinoid signaling, because it is an important modulator of neuron and astrocyte functions, as well as brain ageing. We demonstrate that mice with a specific deletion of CB1 receptors on GABAergic neurons (GABA-Cnr1-/- mice), which show a phenotype of accelerated brain ageing, affects age-related changes in the morphology of astrocytes in the hippocampus. Thus, GABA-Cnr1-/- mice showed a much more pronounced age-related and layer-specific increase in GFAP-positive areas in the hippocampus compared to wild-type animals. The number of astrocytes, in contrast, was similar between the two genotypes. Astrocytes in the hippocampus of old GABA-Cnr1-/- mice also showed a different morphology with enhanced GFAP-positive process branching and a less polarized intrahippocampal distribution. Furthermore, astrocytic TNFα levels were higher in GABA-Cnr1-/- mice, indicating that these morphological changes were accompanied by a more pro-inflammatory function. These findings demonstrate that the disruption of endocannabinoid signaling on GABAergic neurons is accompanied by functional changes in astrocyte activity, which are relevant to brain ageing. |
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| Item Description: | Gesehen am 26.08.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0202566 |