Ameliorative effect of alendronate against intracerebroventricular streptozotocin induced alteration in neurobehavioral, neuroinflammation and biochemical parameters with emphasis on Aβ and BACE-1

Zameer, Saima; Kaundal, Madhu; Vohora, Divya; Ali, Javed; Najmi, Abul Kalam; Akhtar, Mohd

doi:10.1016/j.neuro.2018.11.012

Cited by 30 publications

(22 citation statements)

References 58 publications

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“…Thirty days after TAM administration (Fig. 1A ) 30 , mice in sham groups received two intracerebroventricular (ICV) infusions of citrate buffer; mice in STZ groups received bilateral ICV infusions of STZ at a dose of 3 mg/kg at interval of 48 h 33 ; mice in STZ + LPS groups received STZ infusions followed by intraperitoneal injection of LPS (1 mg/kg, Sigma, USA); mice in STZ + MCC950 groups received STZ infusions followed by intraperitoneal administration of MCC950 (50 mg/kg, Sigma, USA) 34 , 35 . The experiment was designed in compliance with the ARRIVE guidelines and no exclusion of data was done.…”

Section: Methodsmentioning

confidence: 99%

NLRP3-dependent microglial training impaired the clearance of amyloid-beta and aggravated the cognitive decline in Alzheimer’s disease

et al. 2020

Cell Death Dis

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Alzheimer’s disease (AD), the most common form of dementia, is marked by progressive cognitive decline, deposition of misfolded amyloid-β (Aβ) peptide and formation of neurofibrillary tangles. Recently, microglial training has emerged as an important contributor to neurological diseases, which augments the subsequent inflammation. However, how it affects the pathology of AD remains unknown. Here, using a mouse model of sporadic Alzheimer’s disease (SAD) induced by streptozotocin injection, we demonstrated that microglial training exacerbated Aβ accumulation, neuronal loss, and cognitive impairment. In addition, we injected MCC950 to inhibit NLRP3 activation and used an inducible Cre recombinase to delete the NLRP3 gene in microglia. Inhibition or depletion of microglial NLRP3 could protect against the pathologies of SAD and abolish the effects of microglial training. Our results identified microglial training as an important modifier of neuropathology in SAD and demonstrated that activation of NLRP3 inflammasome contributed to the pathologies and microglial training in SAD. Therefore, NLRP3 could be a potential therapeutic target for SAD treatment.

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Section: Methodsmentioning

confidence: 99%

NLRP3-dependent microglial training impaired the clearance of amyloid-beta and aggravated the cognitive decline in Alzheimer’s disease

et al. 2020

Cell Death Dis

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“…Multiple drugs were found to increase the expression of Let-7 in various cell lines (Lozier et al, 2015;Francess et al, 2018), an example of which is Letrozole (Shibahara et al, 2012;Cho et al, 2016), which is a potent aromatase inhibitor that can cross the BBB (Dave et al, 2013). Controversial data exist regarding the effects of aromatase inhibitors (AIs), including Letrozole, on memory in rodents (Alejandre- Gomez et al, 2007;Aydin et al, 2008;Nayebi et al, 2014 andZameer andVohora, 2017).…”

Section: Discussionmentioning

confidence: 99%

Effect of Letrozole on hippocampal let-7 microRNAs and their correlation with working memory and phosphorylated Tau protein level in an Alzheimer's disease rat model

Moustafa¹,

El-Sayed²,

Abd-Allah³

et al. 2021

Preprint

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Let-7 microRNAs may contribute to neurodegeneration, including Alzheimer's disease (AD), but, they were not investigated in Streptozotocin (STZ)-induced AD. Letrozole increases the expression of Let-7 in cell lines, with conflicting evidence regarding its effects on memory. This study examined Let-7 microRNAs in STZ-induced AD, their correlation with memory and hyperphosphorylated Tau (p-Tau) and the effects of Letrozole on them. Seven groups of adult Sprague Dawley rats were used: Intact, Letrozole, Letrozole Vehicle, STZ (with AD induced by intracerebroventricular injection of STZ in artificial CSF), CSF Control, STZ + Letrozole (STZ-L), and CSF + Letrozole Vehicle. Alternation percentage in T-maze was used as a measure of working memory. Let-7a, b and e and p-Tau levels in the hippocampus were estimated using qRT-PCR and ELISA, respectively. There were significant decreases in alternation percentage and increase in p-Tau in the STZ, Letrozole and STZ-L groups. Expression levels of all studied microRNAs were significantly elevated in the Letrozole and the STZ + L groups, with no difference between the two, suggesting that this elevation was due to Letrozole. Negative correlations were found between alternation percentage and the levels of all studied microRNAs, while positive ones were found between p-Tau concentration and the levels of studied microRNAs. These findings support the theory that Letrozole aggravates pre-existing lesions and add to the evidence of Let-7 neurotoxicity.

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“… 18 β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) represents a key enzyme associated with the formation of Aβ in the hippocampus of rats. 19 A previous study provided evidence demonstrating exposure to Aβ induces tau phosphorylation in hippocampal neurons. 20 Existing literature has revealed that acetylcholinesterase (AchE) is co-localized with hyperphosphorylated tau (P-tau) within neurofibrillary tangles in AD, and that high tau phosphorylation could result in increased AchE content during the initial phases of AD.…”

Section: Introductionmentioning

confidence: 99%

Epigallocatechin-3-Gallate Provides Protection Against Alzheimer’s Disease-Induced Learning and Memory Impairments in Rats

Nan¹,

Wang²,

Zhang³

et al. 2021

DDDT

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Purpose: Recent evidence has highlighted the anti-inflammatory properties of the constituent of Green Tea Polyphenols (GTP), epigallocatechin-3-gallate (EGCG) which has been suggested to exert a neuroprotective effect on Alzheimer's disease (AD). The current study aimed to elucidate the effect of EGCG on memory function in rats with AD. Methods: AD rat models were initially established through an injection with Aβ 25-35 solution, followed by gavage with EGCG at varying doses to determine the effect of EGCG on learning and cognitive deficits in AD. Morris water maze test was conducted to evaluate the spatial memory function of the rats. Immunohistochemistry and Western blot analysis were performed to identify Tau phosphorylation. The expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA and protein in rat hippocampus was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Acetylcholinesterase (AchE) activity, Aβ1-42 expression and Ach content were all detected using enzyme-linked immunosorbent assay (ELISA). Results: EGCG intervention brought about a decrease in the escape latency period while increasing the time at the target quadrant among the AD rats. EGCG decreased the hyperphosphorylation of Tau in hippocampus. BACE1 expression and activity as well as the expression of Aβ1-42 were suppressed by EGCG. Moreover, EGCG promoted Ach content by diminishing the activity of AchE. Conclusion:The current study demonstrates that EGCG may diminish the hyperphosphorylation of the Tau protein, downregulate BACE1 and Aβ1-42 expression to improve the antioxidant system and learning and memory function of rats with AD.

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Ameliorative effect of alendronate against intracerebroventricular streptozotocin induced alteration in neurobehavioral, neuroinflammation and biochemical parameters with emphasis on Aβ and BACE-1

Cited by 30 publications

References 58 publications

NLRP3-dependent microglial training impaired the clearance of amyloid-beta and aggravated the cognitive decline in Alzheimer’s disease

NLRP3-dependent microglial training impaired the clearance of amyloid-beta and aggravated the cognitive decline in Alzheimer’s disease

Effect of Letrozole on hippocampal let-7 microRNAs and their correlation with working memory and phosphorylated Tau protein level in an Alzheimer's disease rat model

Epigallocatechin-3-Gallate Provides Protection Against Alzheimer’s Disease-Induced Learning and Memory Impairments in Rats

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