Hippocampal Deficits in Amyloid-β-Related Rodent Models of Alzheimer’s Disease

Vyas, Yukti; Montgomery, Johanna M.; Cheyne, Juliette E.

doi:10.3389/fnins.2020.00266

Cited by 56 publications

(49 citation statements)

References 217 publications

(239 reference statements)

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“…Using hippocampal brain slices, we examined the expression of long-term potentiation (LTP) by recordings of field excitatory postsynaptic potentials (fEPSPs). Consistent with previous reports, recordings from APP/PS1 mice showed a significant reduction in LTP expression when compared with the wild-type mice ( Gelman et al., 2018 ; Gengler et al., 2010 ; Da Silva et al., 2016 ; Trinchese et al., 2004 ; Vargas et al., 2014 ; Vyas et al., 2020 ) ( Figures 6 A and 6B). However, APP/PS1 mice expressing viral GFP-GluA1-4KQ had substantially improved LTP, whereas expression of GFP-GluA1-WT showed some rescue but to a lesser extent ( Figures 6 A and 6B).…”

Section: Resultssupporting

confidence: 92%

Acetylation of AMPA Receptors Regulates Receptor Trafficking and Rescues Memory Deficits in Alzheimer's Disease

et al. 2020

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Summary In Alzheimer's disease (AD), decreases in the amount and synaptic localization of AMPA receptors (AMPARs) result in weakened synaptic activity and dysfunction in synaptic plasticity, leading to impairments in cognitive functions. We have previously found that AMPARs are subject to lysine acetylation, resulting in higher AMPAR stability and protein accumulation. Here we report that AMPAR acetylation was significantly reduced in AD and neurons with Aβ incubation. We identified p300 as the acetyltransferase responsible for AMPAR acetylation and found that enhancing GluA1 acetylation ameliorated Aβ-induced reductions in total and cell-surface AMPARs. Importantly, expression of acetylation mimetic GluA1 (GluA1-4KQ) in APP/PS1 mice rescued impairments in synaptic plasticity and memory. These findings indicate that Aβ-induced reduction in AMPAR acetylation and stability contributes to synaptopathy and memory deficiency in AD, suggesting that AMPAR acetylation may be an effective molecular target for AD therapeutics.

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Section: Resultssupporting

confidence: 92%

Acetylation of AMPA Receptors Regulates Receptor Trafficking and Rescues Memory Deficits in Alzheimer's Disease

et al. 2020

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“…They perform significant function in the in-born immunological response and swiftly react to injury, generating mediators of inflammation (Akiyama et al, 2000;Leszek et al, 2016). Various animal models have been utilized in determining not just the biological mechanisms of inflammation in Alzheimer's disease (Akiyama et al, 2000;Hickman et al, 2008), but also its behavioral impacts (Lee et al, 2008;Thirumangalakudi et al, 2008;Vyas et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

6‐Gingerol, an active constituent of ginger, attenuates lipopolysaccharide‐induced oxidation, inflammation, cognitive deficits, neuroplasticity, and amyloidogenesis in rat

Adetuyi

Farombi

2021

J. Food Biochem.

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This study examined the protective effect of 6-Gingerol (6G) against lipopolysaccharide (LPS)-induced cognitive impairments, oxidative stress, neuroplasticity, amyloidogenesis, and inflammation. Male rats were allocated into six groups in this manner; Group I placed on normal saline only. Group II was treated for 7 days with LPS alone intraperitoneally at 250 µg/kg body weight (bw). Group III received 6G alone at 50 mg/kg bw orally for 14 days. Groups IV and V received 6G at 20 and 50 mg/kg bw for 7 days, respectively, and LPS for another 7 days to induce neurotoxicity. Group VI received 5 mg/kg bw of donepezil for 7 days and LPS for 7 days. Pretreatment with 20 and 50 mg/kg bw of 6G protected against LPS-mediated learning and memory function, and also locomotor and motor deficits. Besides, 20 and 50 mg/kg bw 6G mitigated LPS-induced alteration in markers of oxidative stress. Furthermore, induction of amyloidogenesis associated with disruption of histoarchitecture and high expression of interleukin 1β, inducible nitric oxide synthase, amyloid precursor protein (APP), β-secretase 1, and brain-derived neurotrophic factor by LPS was mitigated by the two doses of 6G in the rat hippocampus and cerebral cortex region of the brain. 6G pretreatment at the two doses mitigated LPS-mediated histopathological changes in the hippocampus and cerebral cortex of rats. Overall, our results demonstrate that the protective effect of 6G is mediated through the reversal of neurobehavioral deficit, oxidative stress, inflammation, and amyloidogenesis, thus making 6G a possible chemoprophylactic agent against brain injury as a result of LPS exposure. Practical applicationsIn the search for a holistic prevention of inflammation-associated neurodegeneration, nutraceuticals are becoming prominent. Hence, this study presents 6G, an active constituent of ginger, as a chemoprotective, antioxidant, and anti-inflammatory agent, which is able to ameliorate cognitive impairments, oxidative stress, neuroplasticity, amyloidogenesis, and inflammation in LPS-induced rat model of neuroinflammation.

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“…In addition, the pathway by which Pg or bacterial products cross the BBB and enter the CNS remains unclear. A ligature-induced PD mouse model is useful for investigating sustained periodontal inflammation in CNS because it exhibits sustained inflammatory cytokine expression in gingival tissue, and the accumulation of bacteria from ligature could not influence systemic conditions [ 32 ]. Furthermore, the hippocampus is primarily involved in memory formation.…”

Section: Introductionmentioning

confidence: 99%

IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier

et al. 2020

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Background: Periodontal disease (PD) is a risk factor for systemic diseases, including neurodegenerative diseases. The role of the local and systemic inflammation induced by PD in neuroinflammation currently remains unclear. The present study investigated the involvement of periodontal inflammation in neuroinflammation and blood–brain barrier (BBB) disruption. Methods: To induce PD in mice (c57/BL6), a ligature was placed around the second maxillary molar. Periodontal, systemic, and neuroinflammation were assessed based on the inflammatory cytokine mRNA or protein levels using qPCR and ELISA. The BBB permeability was evaluated by the mRNA levels and protein levels of tight junction-related proteins in the hippocampus using qPCR and immunofluorescence. Dextran tracing in the hippocampus was also conducted to examine the role of periodontal inflammation in BBB disruption. Results: The TNF-α, IL-1β, and IL-6 levels markedly increased in gingival tissue 1 week after ligation. The IL-6 serum levels were also increased by ligature-induced PD. In the hippocampus, the IL-1β mRNA expression levels were significantly increased by ligature-induced PD through serum IL-6. The ligature-induced PD decreased the claudin 5 expression levels in the hippocampus, and the neutralization of IL-6 restored its levels. The extravascular 3-kDa dextran levels were increased by ligature-induced PD. Conclusions: These results suggest that the periodontal inflammation-induced expression of IL-6 is related to neuroinflammation and BBB disruption in the hippocampus, ultimately leading to cognitive impairment. Periodontal therapy may protect against neurodegenerative diseases.

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Hippocampal Deficits in Amyloid-β-Related Rodent Models of Alzheimer’s Disease

Cited by 56 publications

References 217 publications

Acetylation of AMPA Receptors Regulates Receptor Trafficking and Rescues Memory Deficits in Alzheimer's Disease

Acetylation of AMPA Receptors Regulates Receptor Trafficking and Rescues Memory Deficits in Alzheimer's Disease

6‐Gingerol, an active constituent of ginger, attenuates lipopolysaccharide‐induced oxidation, inflammation, cognitive deficits, neuroplasticity, and amyloidogenesis in rat

IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier

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