期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 34, 期 4, 页码 873-885出版社
IOS PRESS
DOI: 10.3233/JAD-121714
关键词
Alzheimer's disease; hippocampus; long-term memory; neural progenitor cells; neurogenesis; tetrahydrohyperforin
资金
- FONDEF [D07I1052]
- FONDECYT [1120156, 11110012]
- Basal Center of Excellence in Aging and Regeneration [CONICYT-PFB12/2007]
- Insertion of Post-doctoral Researchers in the Academy (CONICYT) [79090027]
- MECESUP
Tetrahydrohyperforin (IDN5706), a semi-synthetic derivative of hyperforin, has shown neuroprotective properties preventing the impairment of synaptic plasticity and cognitive decline in an in vivo model of Alzheimer's disease (AD). Considering the reported role of adult neurogenesis in the plasticity of the hippocampal network, we investigated whether IDN5706 affects adult neurogenesis and hippocampal function. In hippocampal progenitors cultured from adult rats, IDN5706 increased proliferation. Moreover, treatment with IDN5706 for 4 weeks increased cell proliferation in the subgranular zone (SGZ) of the hippocampus in 2 month-old wild-type mice in vivo. As determined by double labeling with BrdU and neuronal markers, IDN5706 treatment increased the number of immature neurons and newborn mature neurons in the adult dentate gyrus. In addition, IDN5706 treatment improved long-term memory in a hippocampal-dependent spatial memory task. Finally, IDN5706 treatment increased cell proliferation and neural commitment in the SGZ of the double transgenic APPswe/PS1 Delta E9 mouse model of AD. These results indicate that IDN5706 increases adult hippocampal neurogenesis and may have therapeutic value in neurological disorders in which adult neurogenesis is impaired.
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