Effects of a new synthetic butyrylcholinesterase inhibitor, HBU-39, on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia animal model

Yoo, Dae Young; Woo, Yeun Ji; Kim, Woosuk; Nam, Sung Min; Lee, Bo Hyun; Yeun, Go Heum; Yoon, Yeo Sung; Won, Moo‐Ho; Park, Jeong Ho; Hwang, In Koo

doi:10.1016/j.neuint.2011.06.021

Cited by 12 publications

(5 citation statements)

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“…Furthermore, AChE inhibitors, such as donepezil hydrochloride, have been shown to enhance neurogenesis via downregulation of AChE activity in mice with vascular dementia [61, 62]. Finally, we have previously demonstrated that inhibition of AChE or butyrylcholinesterase activity significantly increases the cell proliferation and neuroblast differentiation in the dentate gyrus [63]. …”

Section: Discussionmentioning

confidence: 99%

Essential oils from two Allium species exert effects on cell proliferation and neuroblast differentiation in the mouse dentate gyrus by modulating brain-derived neurotrophic factor and acetylcholinesterase

Jung

Lee

Yoo

et al. 2016

BMC Complement Altern Med

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BackgroundIn the present study, we investigated the effects of oil products from two Allium species: Allium sativum (garlic) and Allium hookeri (Chinese chives) on cell proliferation and neuroblast differentiation in the mouse dentate gyrus.MethodsUsing corn oil as a vehicle, the essential oil from garlic (10 ml/kg), or Chinese chives (10 ml/kg) was administered orally to 9-week-old mice once a day for 3 weeks. One hour following the last treatment, a novel object recognition test was conducted and the animals were killed 2 h after the test.ResultsIn comparison to the vehicle-treated group, garlic essential oil (GO) treatment resulted in significantly increased exploration time and discrimination index during the novel object recognition test, while Chinese chives essential oil (CO) reduced the exploration time and discrimination index in the same test. In addition, the number of Ki67-immunoreactive proliferating cells and doublecortin-immunoreactive neuroblasts significantly increased in the dentate gyrus of GO-treated animals. However, administration of CO significantly decreased cell proliferation and neuroblast differentiation. Administration of GO significantly increased brain-derived neurotrophic factor (BDNF) levels and decreased acetylcholinesterase (AChE) activity in the hippocampal homogenates. In contrast, administration of CO decreased BDNF protein levels and had no significant effect on AChE activity, compared to that in the vehicle-treated group.ConclusionsThese results suggest that GO significantly improves novel object recognition as well as increases cell proliferation and neuroblast differentiation, by modulating hippocampal BDNF protein levels and AChE activity, while CO impairs novel object recognition and decreases cell proliferation and neuroblast differentiation, by reducing BDNF protein levels in the hippocampus.

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Section: Discussionmentioning

confidence: 99%

Essential oils from two Allium species exert effects on cell proliferation and neuroblast differentiation in the mouse dentate gyrus by modulating brain-derived neurotrophic factor and acetylcholinesterase

Jung

Lee

Yoo

et al. 2016

BMC Complement Altern Med

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“…After this period, animals were anesthesized using chlorpent (2 ml/kg) and a 0.5 cm incision was made on the abdominal skin. Alzet osmotic pumps (Durect Co., Cupertino, CA) containing 2 ml saline, or 440 mg/ml of SCO solution were subcutaneously embedded in abdominal wall as previously described [32], [33]. SCO release (0.25 µl/h) was maintained for 28 days and administration of LBPs was continued as before throughout SCO treatment.…”

Section: Methodsmentioning

confidence: 99%

Lycium barbarum Polysaccharides Prevent Memory and Neurogenesis Impairments in Scopolamine-Treated Rats

et al. 2014

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Lycium barbarum is used both as a food additive and as a medicinal herb in many countries, and L. barbarum polysaccharides (LBPs), a major cell component, are reported to have a wide range of beneficial effects including neuroprotection, anti-aging and anticancer properties, and immune modulation. The effects of LBPs on neuronal function, neurogenesis, and drug-induced learning and memory deficits have not been assessed. We report the therapeutic effects of LBPs on learning and memory and neurogenesis in scopolamine (SCO)-treated rats. LBPs were administered via gastric perfusion for 2 weeks before the onset of subcutaneous SCO treatment for a further 4 weeks. As expected, SCO impaired performance in novel object and object location recognition tasks, and Morris water maze. However, dual SCO- and LBP-treated rats spent significantly more time exploring the novel object or location in the recognition tasks and had significant shorter escape latency in the water maze. SCO administration led to a decrease in Ki67- or DCX-immunoreactive cells in the dentate gyrus and damage of dendritic development of the new neurons; LBP prevented these SCO-induced reductions in cell proliferation and neuroblast differentiation. LBP also protected SCO-induced loss of neuronal processes in DCX-immunoreactive neurons. Biochemical investigation indicated that LBP decreased the SCO-induced oxidative stress in hippocampus and reversed the ratio Bax/Bcl-2 that exhibited increase after SCO treatment. However, decrease of BDNF and increase of AChE induced by SCO showed no response to LBP administration. These results suggest that LBPs can prevent SCO-induced cognitive and memory deficits and reductions in cell proliferation and neuroblast differentiation. Suppression of oxidative stress and apoptosis may be involved in the above effects of LBPs that may be a promising candidate to restore memory functions and neurogenesis.

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“…In fact, the memory impairment produced in rats following intraperitoneal injections of scopolamine resembles the clinical symptoms of AD patients [ 38 ]. Scopolamine influences the expression of several genes associated with muscarinic receptor signaling pathways, apoptosis, and cell differentiation in the rat brain [ 39 ]. The 2VO/H technique aimed to model global cerebral ischemia, which occurs in VD patients and essentially comprises both permanent bilateral CCA occlusion and hypovolemic conditioning.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, the memory impairment produced in rats following intraperitoneal injections of scopolamine resembles the clinical symptoms of AD patients [38]. Scopolamine influences the expression of several genes associated with muscarinic receptor signaling pathways, apoptosis, and cell differentiation in the rat brain [39] nique aimed to model global cerebral ischemia, which occurs in VD patients and essentially comprises both permanent bilateral CCA occlusion and hypovolemic conditioning. This model produces pathophysiologic changes including ischemic neuronal damage, neuroinflammatory changes in the hippocampus, and the impairment of hippocampus-related behaviors such as cognition, spatial learning, and memory [40].…”

Section: Discussionmentioning

confidence: 99%

Aster ageratoidesTurcz. extract attenuates Alzheimer’s disease-associated cognitive deficits and vascular dementia-associated neuronal death

Jeong

Lee

et al. 2020

Anat Cell Biol

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Dementia is the common neurodegenerative disorder affecting the elderly, with a progressive cognitive decline and memory loss. Since Alzheimer’s disease (AD) and vascular dementia (VD) share key pathologies including oxidative damage, oral supplement of phytochemical medicines, which are well-known for their antioxidant properties, can be a viable therapy for both types of dementia. In this study, the therapeutic potential of the Aster ageratoides extract (AAE), an oriental drug with multiple medicinal properties, was tested on experimental rat models of AD and VD. After confirming the in vitro attenuation of neuronal excitotoxicity by AAE, rats were orally administered with AAE for 7 days and subsequently tested under 2 different experimental paradigms: efficacy screening against #1 AD and #2 VD. For paradigm #1, the rats received intraperitoneal scopolamine and subsequently underwent 3 different behavior tests i.e., the Y-maze, novel object recognition, and passive avoidance tests. For paradigm #2, the rats were operated with the 2-vessel occlusion and hypovolemia (2VO/H) technique, and at postoperative day 7, their hippocampal neuronal viability and the neuroinflammatory changes were quantified. The results showed that the scopolamine-induced impairment of memory performance was significantly improved by AAE intake. Furthermore, while the 2VO/H operation induced marked hippocampal neuronal death and microglial activation, both these effects were significantly attenuated by AAE supplements. Some of the aforementioned effects of AAE intake were dose-dependent. These results provided evidence that AAE supplements can exert anti-AD and -VD efficacies and suggested that AAE might be used as an edible phytotherapeutic for the 2 major types of dementia.

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Effects of a new synthetic butyrylcholinesterase inhibitor, HBU-39, on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia animal model

Cited by 12 publications

References 46 publications

Essential oils from two Allium species exert effects on cell proliferation and neuroblast differentiation in the mouse dentate gyrus by modulating brain-derived neurotrophic factor and acetylcholinesterase

Essential oils from two Allium species exert effects on cell proliferation and neuroblast differentiation in the mouse dentate gyrus by modulating brain-derived neurotrophic factor and acetylcholinesterase

Lycium barbarum Polysaccharides Prevent Memory and Neurogenesis Impairments in Scopolamine-Treated Rats

Aster ageratoidesTurcz. extract attenuates Alzheimer’s disease-associated cognitive deficits and vascular dementia-associated neuronal death

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