Osthole improves chronic cerebral hypoperfusion induced cognitive deficits and neuronal damage in hippocampus

Ji, Hai-Jie; Hu, Jin‐Feng; Wang, Yonghui; Chen, Xiaoyu; Zhou, Ran; Chen, Nai‐Hong

doi:10.1016/j.ejphar.2010.03.038

Cited by 87 publications

(55 citation statements)

References 37 publications

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“…13,14) Memory impairments were seen as early as 7 months of age, 43) thus, in the present study, we used APP/PS1 mice at age of 8-9 months. Osthole, an active constituent of Angelica Pubescentis Radix (R. angelicae pubescentis) and Cnidium monnieri (L.) CUS-SON, has been reported to exert neuroprotective effects [21][22][23][24][25][26] and possess the capable of improvement of neural stem cell proliferation. 27) Recently, osthole also has been reported to reverse Aβ neurotoxicity by stimulating BDNF production and enhancing CREB phosphorylation in cultured cortical neurons.…”

Section: Discussionmentioning

confidence: 99%

“…21) It has been previously reported that osthole exerts neuroprotective effects in some experimental models of cerebral ischemia/reperfusion and brain injury via anti-oxidative and anti-inflammatory activities, [22][23][24][25][26] and it attenuates clinical severity and demyelination of experimental autoimmune encephalomyelitis (EAE) in mice. 27) Recently osthole has been reported to be capable of improving the proliferation of neural stem cells (NSCs) in vitro and enhancing the expression of BDNF in the CNS, 28) displaying a promising capacity to augment adult hippocampal neurogenesis in AD.…”

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confidence: 99%

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

Liu

Xue

Shi

et al. 2015

Biological & Pharmaceutical Bulletin

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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.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Liu

Xue

Shi

et al. 2015

Biological & Pharmaceutical Bulletin

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“…Besides, other mechanisms including oxidative stress and inflammatory responses may also contribute to the pathophysiology of chronic cerebral hypoperfusion. Antioxidants, such as green tea polyphenols, and immunosuppressive drugs, such as cyclosporin A and FK-506, have protective effects and attenuated cognitive impairment in 2VO rats, suggesting the role of oxidative stress and inflammation in chronic cerebral hypoperfusion [52][53][54] . In conclusion, the ceftriaxone treatment improved spatial learning and memory performance in the Morris water maze, and increased hippocampal CA1 and CA3 neuronal number in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Ceftriaxone improves spatial learning and memory in chronic cerebral hypoperfused rats

Koomhin¹,

Tilokskulchai²,

Tapechum

2012

ScienceAsia

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Cerebral hypoperfusion is associated with cognitive decline in ageing, mild cognitive impairment, vascular type dementia, and Alzheimer's disease. The mechanisms leading to such neurological impairments are still uncertain. Although several mechanisms have been proposed as contributing factors leading to neuronal injury, glutamate excitotoxicity seems to be the relevant one. Recently, it was found that β-lactam antibiotics such as ceftriaxone show a neuroprotective effect by upregulation of glutamate transporter and reduction of glutamate excitotoxicity. To study the contribution of glutamate excitotoxicity and the effects of ceftriaxone on spatial learning and memory in chronic cerebral hypoperfusion, we conducted experiments in rats subjected to permanent bilateral common carotid artery occlusion. Ceftriaxone (200 mg/kg) was injected daily in rats for 5 days after the onset of the arterial ligation. A Morris water maze was used to assess learning and memory two months after arterial ligation. Hippocampal histology and glutamate transporter 1 (GLT-1) expression were also studied. Results showed that ceftriaxone improved learning and memory performance. Consistently, the histological study showed an increase hippocampal CA1 and CA3 neuronal numbers in the ceftriaxone-treated group compared with the vehicle-treated group. Although not statistically significant, the GLT-1 protein level in the hippocampus was 86% higher than the sham group. We conclude that ceftriaxone treatment can attenuate neuronal injury and improve spatial learning and memory after chronic cerebral hypoperfusion and that glutamate excitotoxicity may play an important role in the pathophysiology of chronic cerebral hypoperfusion.

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“…35,60) A volume of interesting studies have revealed the neuroprotective effects of Ost on some experimental models of cerebral ischemia/reperfusion and brain injury via anti-oxidative and anti-inflammatory activities. 33,35,60) Also Ost attenuated clinical severity and CNS inflammation and demyelination of EAE mice by blocking reduction of NGF and suppressed IFN-γ increase. 36) In spite of the large volume of known activities of Ost, its effect on adult hippocampal neurogenesis is still remained unknown.…”

Section: Discussionmentioning

confidence: 99%

The Coumarin Derivative Osthole Stimulates Adult Neural Stem Cells, Promotes Neurogenesis in the Hippocampus, and Ameliorates Cognitive Impairment in APP/PS1 Transgenic Mice

Kong

Yao

et al. 2015

Biological & Pharmaceutical Bulletin

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It is believed that neuronal death caused by abnormal deposition of amyloid-beta peptide is the major cause of the cognitive decline in Alzheimer's disease. Adult neurogenesis plays a key role in the rescue of impaired neurons and amelioration of cognitive impairment. In the present study, we demonstrated that osthole, a natural coumarin derivative, was capable of promoting neuronal stem cell (NSC) survival and inducing NSC proliferation in vitro. In osthole-treated APP/PS1 transgenic mice, a significant improvement in learning and memory function was seen, which was associated with a significant increase in the number of new neurons (Ki67 /NF-M ) and a decrease in apoptotic cells in the hippocampal region of the brain. These observations suggested that osthole promoted NSC proliferation, supported neurogenesis, and thus efficiently rescued impaired neurons in the hippocampus and ameliorated cognitive impairment. We also found that osthole treatment activated the Notch pathway and upregulated the expression of self-renewal genes Notch 1 and Hes 1 mRNA in NSCs. However, when Notch activity was blocked by the γ-secretase inhibitor DAPT, the augmentation of Notch 1 and Hes 1 protein was ameliorated, and the proliferation-inducing effect of osthole was abolished, suggesting that the effects of osthole are at least in part mediated by activation of the Notch pathway.

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Osthole improves chronic cerebral hypoperfusion induced cognitive deficits and neuronal damage in hippocampus

Cited by 87 publications

References 37 publications

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

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

Ceftriaxone improves spatial learning and memory in chronic cerebral hypoperfused rats

The Coumarin Derivative Osthole Stimulates Adult Neural Stem Cells, Promotes Neurogenesis in the Hippocampus, and Ameliorates Cognitive Impairment in APP/PS1 Transgenic Mice

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