The dentate gyrus of the hippocampus is one of two brain areas generating throughout life new neurons, which contribute to the formation of episodic/associative memories. During aging the production of new neurons from stem cells decreases and a cognitive decline occurs. Our studies are aimed at defining the gene network and neurogenic stimuli regulating stem cell activation, especially during aging. Dietary factors influence neuronal function and synaptic plasticity; among them the phenolic compound Hydroxytyrosol (HTyr), present in olive oil, displays neuroprotective effects. Since age impacts primarily on the hippocampus-dependent cognitive processes, we asked whether HTyr could stimulate hippocampal neurogenesis in vivo in adult and aged wild-type mice as well as in the Btg1 knockout mouse model of accelerated neural aging. We found that treatment with HTyr activates neurogenesis in the dentate gyrus of adult, aged and Btg1-null mice, by increasing survival of new neurons and decreasing apoptosis. Notably, however, in the aged and Btg1-null dentate gyrus, HTyr treatment also stimulates the proliferation of stem and progenitor cells, whereas in the adult dentate gyrus HTyr lacks any proliferative effect. Moreover, the new neurons generated in aged mice after HTyr treatment are recruited to existing circuits, as shown by the increase of BrdU+/c-fos+ neurons. Finally, HTyr treatment also reduces the markers of aging lipofuscin and Iba1. Overall, our findings indicate that HTyr treatment counteracts neurogenesis decline during aging. HTyr is thus a neurogenic stimulus able to activate stem cells even during aging, indcating that the threshold of stem cell activation is dependente on the stimulus and the condition of the neurogenic niche.
Hydroxytyrosol stimulates neurogenesis in aged dentate gyrus by enhancing stem and progenitor cell proliferation and neuron survival
Tirone F.;D’Andrea Giorgio;Micheli L.
2020
Abstract
The dentate gyrus of the hippocampus is one of two brain areas generating throughout life new neurons, which contribute to the formation of episodic/associative memories. During aging the production of new neurons from stem cells decreases and a cognitive decline occurs. Our studies are aimed at defining the gene network and neurogenic stimuli regulating stem cell activation, especially during aging. Dietary factors influence neuronal function and synaptic plasticity; among them the phenolic compound Hydroxytyrosol (HTyr), present in olive oil, displays neuroprotective effects. Since age impacts primarily on the hippocampus-dependent cognitive processes, we asked whether HTyr could stimulate hippocampal neurogenesis in vivo in adult and aged wild-type mice as well as in the Btg1 knockout mouse model of accelerated neural aging. We found that treatment with HTyr activates neurogenesis in the dentate gyrus of adult, aged and Btg1-null mice, by increasing survival of new neurons and decreasing apoptosis. Notably, however, in the aged and Btg1-null dentate gyrus, HTyr treatment also stimulates the proliferation of stem and progenitor cells, whereas in the adult dentate gyrus HTyr lacks any proliferative effect. Moreover, the new neurons generated in aged mice after HTyr treatment are recruited to existing circuits, as shown by the increase of BrdU+/c-fos+ neurons. Finally, HTyr treatment also reduces the markers of aging lipofuscin and Iba1. Overall, our findings indicate that HTyr treatment counteracts neurogenesis decline during aging. HTyr is thus a neurogenic stimulus able to activate stem cells even during aging, indcating that the threshold of stem cell activation is dependente on the stimulus and the condition of the neurogenic niche.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
