Naringin Enhances CaMKII Activity and Improves Long-Term Memory in a Mouse Model of Alzheimer’s Disease

Abstract Alzheimer’s disease (AD) is a highly disabling condition, with no cure currently available that accounts for 60-70% of all dementia cases worldwide. Therefore, the study of possible therapeutic strategies for AD is required. For that, animal models which resemble the main aspects of AD has been largely employed. Similar to AD patients, the double transgenic APPswe/PS1dE9 (APP/PS1) mice presents amyloid-β (Αβ) plaques in the cortex and hippocampus, hyperlocomotion, cognitive deficits, and exacerbated inflammatory response. Recent studies showed that these neuropathological features were reversed by the transplantation of stem cells. However, the comparison of the effects induced by neural (NSC) or mesenchymal (MSC) stem cells was never investigated in an AD animal model before. In view of that, the present study aimed to evaluate whether NSC or MSC transplantation into the hippocampus of APP/PS1 mice reverse AD-related alterations, namely locomotor activity (open field test), short- and long-term memory (object recognition test), Αβ plaques formation (6-E10 immune staining) and microglia activation (Iba-1 immune staining) in the hippocampus. NSC and MSC engraftment reduced the number of hippocampal Αβ plaques in the hippocampus of APP/PS1 mice, and NSC reverted the peripheral hyperlocomotion activity displayed by APP/PS1 mice. Surprisingly, NSC increased microglia activation in the hippocampus of APP/PS1 mice and no impairment in short or long-term memory was observed in APP/PS1 mice. Altogether, this study reinforces the possible beneficial effects of NSC or MSC transplantation in the AD treatment.

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Behavioral Improvements and its Molecular Mechanism of Ilex kudingcha C.J. Tseng on Animal Model of Alzheimer’s Disease

Majalah Obat Tradisional ◽

10.22146/mot.53686 ◽

2020 ◽

Vol 25 (3) ◽

Author(s):

Lap Thi Nguyen ◽

Nguyen Huu Son ◽

Tran Nguyen Hong ◽

Nguyen Minh Khoi ◽

Kinzo Matsumoto ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Muscarinic Receptor ◽

Short Term Memory ◽

Long Term Memory ◽

Short Term ◽

Reference Drug ◽

Term Memory ◽

Model Of Alzheimer’S Disease

Alzheimer's disease (AD) is a common chronic neurodegenerative disease with well-defined pathophysiological mechanisms. Ilex kudingcha (IK) C.J. Tseng is commonly known as bitter tea or “Khom” tea in Vietnam. The present study was conducted to investigate the anti-dementia effect of IK using olfactory bulbectomized (OBX) mice. OBX mice were daily treated with IK extract (540 mg/kg) or reference drug, tacrine (2.5 mg/kg) 1 week before and continuously for 3 days after the OBX surgery. The object recognition test, modified Y maze test and fear conditioning test were employed to analyze non-spatial short-term, spatial short-term and long-term memories of the mice respectively. Administration of IK extract and tacrine attenuated these OBX-induced cognitive deficits in mice. The effects of IK and tacrine on spatial short-term memory impairment were reversed by scopolamine, a muscarinic receptor antagonist. The amyloid-beta (Aβ) production in adult transgenic Drosophila brain flies was also investigated by using Western blotting with APP-HA antibody. These results indicated that IK extract improves short-term and long-term memory disturbances in OBX mice and that muscarinic receptor may play a role on these actions. In addition, our result also showed that IK extract reduces the expression of amyloid precursor protein (APP) in brain of AD model using Drosophila melanogaster.

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Intensification of long-term memory deficit by chronic stress and prevention by nicotine in a rat model of Alzheimer's disease

Molecular and Cellular Neuroscience ◽

10.1016/j.mcn.2010.06.018 ◽

2010 ◽

Vol 45 (3) ◽

pp. 289-296 ◽

Cited By ~ 22

Author(s):

Karim A. Alkadhi ◽

Marisa Srivareerat ◽

Trinh T. Tran

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Chronic Stress ◽

Rat Model ◽

Memory Deficit ◽

Long Term Memory ◽

Term Memory ◽

Model Of Alzheimer’S Disease

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Disruption of the astrocyte–neuron interaction is responsible for the impairments in learning and memory in 5XFAD mice: an Alzheimer’s disease animal model

Molecular Brain ◽

10.1186/s13041-021-00823-5 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Moonseok Choi ◽

Sang-Min Lee ◽

Dongsoo Kim ◽

Heh-In Im ◽

Hye-Sun Kim ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Model ◽

Memory Formation ◽

Long Term Memory ◽

Term Memory ◽

Stat3 Phosphorylation ◽

Neuron Interactions ◽

5Xfad Mice

AbstractThe morphological dynamics of astrocytes are altered in the hippocampus during memory induction. Astrocyte–neuron interactions on synapses are called tripartite synapses. These control the synaptic function in the central nervous system. Astrocytes are activated in a reactive state by STAT3 phosphorylation in 5XFAD mice, an Alzheimer’s disease (AD) animal model. However, changes in astrocyte–neuron interactions in reactive or resting-state astrocytes during memory induction remain to be defined. Here, we investigated the time-dependent changes in astrocyte morphology and the number of astrocyte–neuron interactions in the hippocampus over the course of long-term memory formation in 5XFAD mice. Hippocampal-dependent long-term memory was induced using a contextual fear conditioning test in 5XFAD mice. The number of astrocytic processes increased in both wild-type and 5XFAD mice during memory formation. To assess astrocyte–neuron interactions in the hippocampal dentate gyrus, we counted the colocalization of glial fibrillary acidic protein and postsynaptic density protein 95 via immunofluorescence. Both groups revealed an increase in astrocyte–neuron interactions after memory induction. At 24 h after memory formation, the number of tripartite synapses returned to baseline levels in both groups. However, the total number of astrocyte–neuron interactions was significantly decreased in 5XFAD mice. Administration of Stattic, a STAT3 phosphorylation inhibitor, rescued the number of astrocyte–neuron interactions in 5XFAD mice. In conclusion, we suggest that a decreased number of astrocyte–neuron interactions may underlie memory impairment in the early stages of AD.

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Prolonged Volatile Anesthetic Exposure Exacerbates Cognitive Impairment and Neuropathology in the 5xFAD Mouse Model of Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-210374 ◽

2021 ◽

pp. 1-12

Author(s):

Fanglei Han ◽

Jia Zhao ◽

Guoqing Zhao

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Volatile Anesthetics ◽

Model Of Alzheimer’S Disease ◽

Short Term Exposure ◽

5Xfad Mouse ◽

Anesthetic Exposure ◽

5Xfad Mice

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease which shows a set of symptoms involving cognitive changes and psychological changes. Given that AD is the most common form of dementia in aging population and the increasing demand for anesthesia/surgery with aging, there has been significant interest in the exact impact of volatile anesthetics on cognitive function and pathological alterations in AD population. Objective: This study aimed to investigate behavioral changes and neuropathology in the 5xFAD mouse model of Alzheimer’s disease with short-term exposure or long-term exposure to desflurane, sevoflurane, or isoflurane. Methods: In this study, we exposed 5xFAD mouse model of AD to isoflurane, sevoflurane, or desflurane in two different time periods (30 min and 6 h), and the memory related behaviors as well as the pathological changes in 5xFAD mice were evaluated 7 days after the anesthetic exposure. Results: We found that short-term exposure to volatile anesthetics did not affect hippocampus dependent memory and the amyloid-β (Aβ) deposition in the brain. However, long-term exposure to sevoflurane or isoflurane significantly increased the Aβ deposition in CA1 and CA3 regions of hippocampus, as well as the glial cell activation in amygdala. Besides, the PSD-95 expression was decreased in 5xFAD mice with exposure to sevoflurane or isoflurane and the caspase-3 activation was enhanced in isoflurane, sevoflurane, and desflurane groups. Conclusion: Our results demonstrate the time-dependent effects of common volatile anesthetics and implicate that desflurane has the potential benefits to prolonged anesthetic exposure in AD patients.

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