Hydroxytyrosol (HTyr), a phenolic compound present in olive oil, exerts a protective effect in several chronic age-associated diseases due to its antioxidant, anti-inflammatory and neuroprotective properties (PMID: 37049607). We previously observed that oral administration of HTyr, in aged mice reactivates stem cells present in the neurogenic niche of the dentate gyrus of the hippocampus and promotes the generation and survival of new neurons (PMID: 32027412). It is known that the dorsal part of the hippocampus is involved in learning and memory, and the ventral part in the response to stress. Moreover, it is now widely recognised that there is a bidirectional microbiota-gut-brain axis, which exerts a significant influence on behaviour and learning. We therefore wondered about the effect of HTyr treatment on the cognitive behaviour of aged mice and the potential contribution of the microbiota. We observed that oral administration of HTyr, synthesised in our laboratory using a procedure we optimised: i) promotes the production of new neurons in both the dorsal and ventral part of the dentate gyrus of the hippocampus, with a prevalent effect in the ventral region; ii) decreases the inflammatory status of microglia; iii) reduces anxiety symptoms in a model of post-traumatic stress disorder, although it is not able to recover the contextual memory decline observed with ageing. In parallel, treatment with HTyr preserves the gut microbiota biodiversity, which tends to decrease after a traumatic event. Specifically, HTyr prevents the decrease in the Ruminococcaceae family, which is known to participate in gut-brain interaction by enhancing serotonin and glutamate biosynthesis, promoting neurogenesis and neuron survival. This suggests that HTyr promotes resilience to stress by increasing neurogenesis directly in the brain and/or through modulation of the microbiota-gut-brain axis. These studies are supported also by Project Lazio Innova 2020 36407.
Hydroxytyrosol mitigates anxiety-like behaviors after a traumatic experience in old mice by promoting neurogenesis in the ventral and dorsal dentate gyrus and by maintaining biodiversity of gut microbiota
Giorgio D’Andrea;Maurizia Caruso;Felice Tirone;Laura Micheli
2024
Abstract
Hydroxytyrosol (HTyr), a phenolic compound present in olive oil, exerts a protective effect in several chronic age-associated diseases due to its antioxidant, anti-inflammatory and neuroprotective properties (PMID: 37049607). We previously observed that oral administration of HTyr, in aged mice reactivates stem cells present in the neurogenic niche of the dentate gyrus of the hippocampus and promotes the generation and survival of new neurons (PMID: 32027412). It is known that the dorsal part of the hippocampus is involved in learning and memory, and the ventral part in the response to stress. Moreover, it is now widely recognised that there is a bidirectional microbiota-gut-brain axis, which exerts a significant influence on behaviour and learning. We therefore wondered about the effect of HTyr treatment on the cognitive behaviour of aged mice and the potential contribution of the microbiota. We observed that oral administration of HTyr, synthesised in our laboratory using a procedure we optimised: i) promotes the production of new neurons in both the dorsal and ventral part of the dentate gyrus of the hippocampus, with a prevalent effect in the ventral region; ii) decreases the inflammatory status of microglia; iii) reduces anxiety symptoms in a model of post-traumatic stress disorder, although it is not able to recover the contextual memory decline observed with ageing. In parallel, treatment with HTyr preserves the gut microbiota biodiversity, which tends to decrease after a traumatic event. Specifically, HTyr prevents the decrease in the Ruminococcaceae family, which is known to participate in gut-brain interaction by enhancing serotonin and glutamate biosynthesis, promoting neurogenesis and neuron survival. This suggests that HTyr promotes resilience to stress by increasing neurogenesis directly in the brain and/or through modulation of the microbiota-gut-brain axis. These studies are supported also by Project Lazio Innova 2020 36407.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
