Reduced ccl11/eotaxin mediates the beneficial effects of environmental stimulation on the aged hippocampus
| Autor: | Scabia, G., Testa, G., Scali, M., Del Turco, S., Desiato, G., Berardi, N., Sale, A., Matteoli, M., Maffei, L., Maffei, M., Mainardi, M., Palumbo, Sara |
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| Přispěvatelé: | Scabia, G., Testa, G., Scali, M., Del Turco, S., Desiato, G., Berardi, N., Sale, A., Matteoli, M., Maffei, L., Maffei, M., Mainardi, M. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Chemokine CCL11
Aging Neurogenesis Immunology Eotaxin Hippocampus Stimulation Hippocampal formation Environment Settore BIO/09 - Fisiologia Learning and memory Inflammation Neural plasticity Animals Mice Spatial Memory Behavioral Neuroscience Neuroplasticity Medicine Cognitive decline CCL11 Environmental enrichment Endocrine and Autonomic Systems business.industry Animal respiratory system Neurogenesi business Neuroscience |
| Popis: | A deterioration in cognitive performance accompanies brain aging, even in the absence of neurodegenerative pathologies. However, the rate of cognitive decline can be slowed down by enhanced cognitive and sensorimotor stimulation protocols, such as environmental enrichment (EE). Understanding how EE exerts its beneficial effects on the aged brain pathophysiology can help in identifying new therapeutic targets. In this regard, the inflammatory chemokine ccl11/eotaxin-1 is a marker of aging with a strong relevance for neurodegenerative processes. Here, we demonstrate that EE in both elderly humans and aged mice decreases circulating levels of ccl11. Interfering, in mice, with the ccl11 decrease induced by EE ablated the beneficial effects on long-term memory retention, hippocampal neurogenesis, activation of local microglia and of ribosomal protein S6. On the other hand, treatment of standard-reared aged mice with an anti-ccl11 antibody resulted in EE-like improvements in spatial memory, hippocampal neurogenesis, and microglial activation. Taken together, our findings point to a decrease in circulating ccl11 concentration as a key mediator of the enhanced hippocampal function resulting from exposure to EE. A deterioration in cognitive performance accompanies brain aging, even in the absence of neurodegenerative pathologies. However, the rate of cognitive decline can be slowed down by enhanced cognitive and sensorimotor stimulation protocols, such as environmental enrichment (EE). Understanding how EE exerts its beneficial effects on the aged brain pathophysiology can help in identifying new therapeutic targets. In this regard, the inflammatory chemokine ccl11/eotaxin-1 is a marker of aging with a strong relevance for neurodegenerative processes. Here, we demonstrate that EE in both elderly humans and aged mice decreases circulating levels of ccl11. Interfering, in mice, with the ccl11 decrease induced by EE ablated the beneficial effects on long-term memory retention, hippocampal neurogenesis, activation of local microglia and of ribosomal protein S6. On the other hand, treatment of standard-reared aged mice with an anti-ccl11 antibody resulted in EE-like improvements in spatial memory, hippocampal neurogenesis, and microglial activation. Taken together, our findings point to a decrease in circulating ccl11 concentration as a key mediator of the enhanced hippocampal function resulting from exposure to EE. |
| Databáze: | OpenAIRE |
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