Osthole Upregulates BDNF to Enhance Adult Hippocampal Neurogenesis in APP/PS1 Transgenic Mice

Abstract

Adult hippocampal neurogenesis occurs in the dentate gyrus (DG) of the mouse hippocampus, and plays roles in learning and memory progresses. In amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice, a rodent model of Alzheimer's disease (AD), severe impairment of neurogenesis in the dentate subgranular zone (SGZ) of the DG has been reported. Osthole, an active constituent of Cnidium monnieri (L.) CUSSON, has been reported to exert neuroprotective effects and may promote neural stem cell proliferation. However, whether osthole ameliorates spatial memory deficits and improves hippocampal neurogenesis in APP/PS1 mice remains unknown. In this study we found that osthole (30 mg/kg intraperitoneally (i.p.) once daily) treatment dramatically ameliorated the cognitive impairments by Morris Water Maze test and passive avoidance test, and augmented neurogenesis in the DG of hippocampus in APP/PS1 mice. Furthermore, osthole treatment upregulated expression of brain-derived neurotrophic factor (BDNF) and enhanced activation of the BDNF receptor tyrosine receptor kinase B (TrkB) following increased phosphorylation of cyclic AMP response element-binding protein (CREB), indicating that osthole improves neurogenesis via stimulating BDNF/TrkB/CREB signaling in APP/PS1 transgenic mice.

Osthole Stimulated Neural Stem Cells Differentiation into Neurons in an Alzheimer's Disease Cell Model via Upregulation of MicroRNA-9 and Rescued the Functional Impairment of Hippocampal Neurons in APP/PS1 Transgenic Mice

“…Herein, we demonstrated a preventive effect after 6 weeks of Ost treatment from the age of 6–7 months in APP/PS1 mice, improving cognition and reducing many AD-associated biomarkers. The results indicated that Ost can significantly ameliorate the learning and memory deficits of mice by reducing the escape latency and the distance to goal, increasing the number of platform crossings and prolonging the time spent in the target quadrant (Figure 6) in the MWM test, consistent with previous reports (Liu et al, 2015). We also examined some biomarkers of AD in the hippocampus of APP/PS1 Tg mice, which is a neurogenesis area in the mammalian brain (Braak et al, 1993).…”

Osthole Enhances the Therapeutic Efficiency of Stem Cell Transplantation in Neuroendoscopy Caused Traumatic Brain Injury

“…77) It has been known that osthole can activate the BDNF/ TrkB signaling and affect the phosphorylation of cyclic AMP response element binding protein (CREB), which might be the underlying mechanisms of the enhancement of neurogenesis. 78) As we observed in the drug treatment group, the expression level of NF-M had been elevated, which relied on the powerful anti-apoptosis function of osthole. So far whether increasing the number of neuronal cells or reducing the apoptosis of neuronal cells can increase the expression of neuronal intermediate filament proteins is still obscure.…”

Potential therapeutic action of natural products from traditional Chinese medicine on Alzheimer's disease animal models targeting neurotrophic factors

“…Cnidium monnieri APP/PS1 transgenic mice are rodent AD models with human APP and PS1 mutations and severe impairment of neurogenesis in the dentate subgranular zone of the dentate gyrus. Intraperitoneally administered osthole (30 mg/kg, PubChem SID: 253999366), an active constituent of the dried seeds of C. monnieri (Order: Apiales, Family: Umbelliferae, Genus: Cnidium), once daily for 28 days, can ameliorate the cognitive impairments in the dentate gyrus of hippocampus, and this function may be associated with stimulating BDNF/TrkB/CREB signal pathway [91]. [76], and AD and shows tremendous potential value in the treatment of nervous system disease.…”