scholarly journals MicroRNA‐134‐5p inhibition rescues long‐term plasticity and synaptic tagging/capture in an Aβ(1–42)‐induced model of Alzheimer’s disease

Aging Cell ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Nimmi Baby ◽  
Nithyakalyani Alagappan ◽  
Shaikali Thameem Dheen ◽  
Sreedharan Sajikumar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Model Of Alzheimer’S Disease

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

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.

Regulation of aberrant proteasome activity re‐establishes plasticity and long‐term memory in an animal model of Alzheimer's disease

2020 ◽  
Vol 34 (7) ◽  
pp. 9466-9479
Author(s):  
Kumar Krishna‐K ◽  
Nimmi Baby ◽  
Radha Raghuraman ◽  
Sheeja Navakkode ◽  
Thomas Behnisch ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Proteasome Activity ◽  
Long Term Memory ◽  
Term Memory ◽  
Model Of Alzheimer’S Disease

scholarly journals TDP-43 interacts with amyloid-β, inhibits fibrillization, and worsens pathology in a model of Alzheimer’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yao-Hsiang Shih ◽  
Ling-Hsien Tu ◽  
Ting-Yu Chang ◽  
Kiruthika Ganesan ◽  
Wei-Wei Chang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Model Of Alzheimer’S Disease ◽  
Term Potentiation ◽  
Spatial Memory Deficit ◽  
Aβ Aggregation ◽  
Intrahippocampal Injection

AbstractTDP-43 inclusions are found in many Alzheimer’s disease (AD) patients presenting faster disease progression and greater brain atrophy. Previously, we showed full-length TDP-43 forms spherical oligomers and perturbs amyloid-β (Aβ) fibrillization. To elucidate the role of TDP-43 in AD, here, we examined the effect of TDP-43 in Aβ aggregation and the attributed toxicity in mouse models. We found TDP-43 inhibited Aβ fibrillization at initial and oligomeric stages. Aβ fibrillization was delayed specifically in the presence of N-terminal domain containing TDP-43 variants, while C-terminal TDP-43 was not essential for Aβ interaction. TDP-43 significantly enhanced Aβ’s ability to impair long-term potentiation and, upon intrahippocampal injection, caused spatial memory deficit. Following injection to AD transgenic mice, TDP-43 induced inflammation, interacted with Aβ, and exacerbated AD-like pathology. TDP-43 oligomers mostly colocalized with intracellular Aβ in the brain of AD patients. We conclude that TDP-43 inhibits Aβ fibrillization through its interaction with Aβ and exacerbates AD pathology.

scholarly journals Metaplasticity mechanisms restore plasticity and associativity in an animal model of Alzheimer’s disease

2017 ◽  
Vol 114 (21) ◽  
pp. 5527-5532 ◽  
Author(s):  
Qin Li ◽  
Sheeja Navakkode ◽  
Martin Rothkegel ◽  
Tuck Wah Soong ◽  
Sreedharan Sajikumar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ryanodine Receptors ◽  
Long Term Potentiation ◽  
Neuronal Population ◽  
Memory Storage ◽  
Dynamic Regulation ◽  
Model Of Alzheimer’S Disease ◽  
Synaptic Tagging And Capture

Dynamic regulation of plasticity thresholds in a neuronal population is critical for the formation of long-term plasticity and memory and is achieved by mechanisms such as metaplasticity. Metaplasticity tunes the synapses to undergo changes that are necessary prerequisites for memory storage under physiological and pathological conditions. Here we discovered that, in amyloid precursor protein (APP)/presenilin-1 (PS1) mice (age 3–4 mo), a prominent mouse model of Alzheimer’s disease (AD), late long-term potentiation (LTP; L-LTP) and its associative plasticity mechanisms such as synaptic tagging and capture (STC) were impaired already in presymptomatic mice. Interestingly, late long-term depression (LTD; L-LTD) was not compromised, but the positive associative interaction of LTP and LTD, cross-capture, was altered in these mice. Metaplastic activation of ryanodine receptors (RyRs) in these neurons reestablished L-LTP and STC. We propose that RyR-mediated metaplastic mechanisms can be considered as a possible therapeutic target for counteracting synaptic impairments in the neuronal networks during the early progression of AD.

PGE 2 -EP3 signaling pathway impairs hippocampal presynaptic long-term plasticity in a mouse model of Alzheimer's disease

2017 ◽  
Vol 50 ◽  
pp. 13-24 ◽  
Author(s):  
Vincent Maingret ◽  
Gaël Barthet ◽  
Séverine Deforges ◽  
Nan Jiang ◽  
Christophe Mulle ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Signaling Pathway ◽  
Model Of Alzheimer’S Disease

scholarly journals Distinct Effects of The Hippocampal Transplantation of Neural And Mesenchymal Stem Cell In a Transgenic Model of Alzheimer’s Disease

2021 ◽  
Author(s):  
Henrique Correia Campos ◽  
Deidiane Elisa Ribeiro ◽  
Debora Hashiguchi ◽  
Deborah Hukuda ◽  
Christiane Gimenes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Amyloid Β ◽  
Microglia Activation ◽  
Long Term Memory ◽  
Object Recognition Test ◽  
Term Memory ◽  
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.

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

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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