Assessment and Validation of Globodera pallida as a Novel In Vivo Model for Studying Alzheimer’s Disease

Althobaiti, Norah A.; Menaa, Farid; Albalawi, Aishah E.; Dalzell, Johnathan J.; Warnock, Neil D.; McCammick, Erin; Alsolais, Abdulellah; Alkhaibari, Abeer M.; Green, Brian D.

doi:10.3390/cells10092481

Cited by 4 publications

(16 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Culture, maintenance, hatching, and testing of G. pallida have been previously described [ 11 ]. Briefly, freshly hatched second-stage juvenile (J2s) nematodes were used in each assay.…”

Section: Methodsmentioning

confidence: 99%

“…There are also potential downstream effects to be explored; for instance, the inhibition of AChE may protect against the damaging effects of Aβ aggregation and its neurotoxicity [ 10 ]. The most promising extracts ( n = 9) were then shortlisted for testing in G. pallida as a novel and suitable non-transgenic model of AD, which is proposed to be a less complicated alternative to transgenic C. elegans models, and to understand the biological mechanisms underlying Aβ pathology [ 11 , 12 ]. This plant parasitic nematode was shown to easily assimilate exogenous amyloid peptides and mimic AD through retrograde transport along the chemosensory amphidal neurons, resulting in impaired behavioural responses to a well-established chemoattractant [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…The most promising extracts ( n = 9) were then shortlisted for testing in G. pallida as a novel and suitable non-transgenic model of AD, which is proposed to be a less complicated alternative to transgenic C. elegans models, and to understand the biological mechanisms underlying Aβ pathology [ 11 , 12 ]. This plant parasitic nematode was shown to easily assimilate exogenous amyloid peptides and mimic AD through retrograde transport along the chemosensory amphidal neurons, resulting in impaired behavioural responses to a well-established chemoattractant [ 11 , 12 ]. The amyloid hypothesis postulates that the neuropathology associated with AD including cognitive decline, dysregulation of energy metabolism, mitochondrial dysfunction, and neuronal cell death correlate with the extracellular deposition of amyloid-β (Aβ) and its associated neurotoxicity [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Aβ (1-42) is the most toxic and shows the greatest propensity to aggregate [ 14 ]. Unsurprisingly, in G. pallida , Aβ (1-42) had the most detrimental effects on chemotaxis, cell viability, survival rate, ROS production, and glutathione levels compared with all other Aβ isoforms [ 11 ]. The present study assessed the ability of selected medicinal plant extracts to mitigate the Aβ (1-42)-induced damage in G. pallida in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…Aβ plaques are thought to cause oxidative stress in AD neurons and increase mitochondrial damage and ROS production, which subsequently leads to neuronal cell death [ 15 ]. The G. pallida model also responded in this way with significantly increased levels of mitochondrial reductase activity, ROS, and glutathione (as an antioxidant defence mechanism) [ 11 ]. Therefore, the present investigation determined whether medicinal plants shortlisted from in vitro studies had therapeutic effects in G. pallida by examining their ability to counteract Aβ-induced impairments in chemotaxis, survival, ROS production, and antioxidant responses.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Ethnomedicinal Plants with Protective Effects against Beta-Amyloid Peptide (Aβ)1-42 Indicate Therapeutic Potential in a New In Vivo Model of Alzheimer’s Disease

et al. 2022

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with unmet medical need. This investigation consisted of testing a range of ethanolic ethnomedicinal plant extracts (n = 18) traditionally used in the treatment of disorders such as anxiety, delirium, and memory loss. They were then screened for in vitro inhibitory activity against acetylcholinesterase (AChE), butylcholinesterase (BuChE), beta-secretase 1/beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), and antioxidant activities. Plants with potent activities were further characterised using a recently developed in vivo model of AD, Globodera pallida. The ability of phytoextracts to protect this organism against amyloid-beta Aβ (1-42) exposure was assessed by measuring chemosensing, survival rate, production of reactive oxygen species (ROS), and antioxidant responses. Extracts (n = 5) from Juglans regia (leaves), Ellettaria cardamomum (seeds), Cinnamomum zeylanicum (bark), Salvia officinalis (leaves/flowers), and Hypericum perforatum (flowers) exerted concentration-dependent inhibitory activities against AChE and BuChE. Three of these plant extracts (i.e., J. regia, E. cardamomum, and S. officinalis) possessed strong concentration-dependent inhibitory activity against BACE1. Furthermore, the five selected medicinal plant extracts not only enhanced significantly (p < 0.05) the nematode’s chemosensing, survival rate, and antioxidant responses (i.e., anti-ROS production, mitochondrial reductase activity, oxidized glutathione (GSSG) to reduced glutathione (GSH) ratio), but also greatly restored (p < 0.05) in a concentration-dependent manner the Aβ (1-42)-induced deleterious changes in these same parameters. In brief, this investigation highlights plant extracts with strong anti-AD activities which could be trialled as novel therapeutic supplements or undergo further biodiscovery research.

show abstract

“…Culture, maintenance, hatching, and testing of G. pallida have been previously described [ 11 ]. Briefly, freshly hatched second-stage juvenile (J2s) nematodes were used in each assay.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ethnomedicinal Plants with Protective Effects against Beta-Amyloid Peptide (Aβ)1-42 Indicate Therapeutic Potential in a New In Vivo Model of Alzheimer’s Disease

et al. 2022

View full text Add to dashboard Cite

show abstract

Neuroprotective effect of nose-to-brain delivery of Asiatic acid in solid lipid nanoparticles and its mechanisms against memory dysfunction induced by Amyloid Beta1-42 in mice

Islamie,

Myint,

Rojanaratha

et al. 2023

BMC Complement Med Ther

View full text Add to dashboard Cite

Background Amyloid-β1-42 (Aβ1-42) plays an essential role in the development of the early stage of Alzheimer’s disease (AD). Asiatic acid (AA), an active compound in Centella asiatica L, exhibit neuroprotective properties in previous studies. Due to its low bioavailability, the nose-to-brain delivery technique was used to enhance AA penetration in the brain. In this study, AA was also loaded in solid lipid nanoparticles (SLNs) as a strategy to increase its absorption in the nasal cavity. Methods Memory impairment was induced via direct intracerebroventricular injection of Aβ1-42 oligomer into mouse brain. The neuroprotective effect and potential underlying mechanisms were investigated using several memory behavioral examinations and molecular techniques. Results The intranasal administration of AA in SLNs attenuated learning and memory impairment induced by Aβ1-42 in Morris water maze and novel object recognition tests. AA significantly inhibited tau hyperphosphorylation of pTau-S396 and pTau-T231 and prevented astrocyte reactivity and microglial activation in the hippocampus of Aβ1-42-treated mice. It is also decreased the high levels of IL-1β, TNF-α, and malondialdehyde (MDA) in mouse brain. Conclusions These results suggested that nose-to-brain delivery of AA in SLNs could be a promising strategy to treat the early stage of AD.

show abstract

Preparation of Memantine-Loaded Chitosan Nanocrystals: In Vitro and Ex Vivo Toxicity Analysis

Saleh

Mohamed²,

Ruby³

et al. 2022

Crystals

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with unmet medical need, and is the leading cause of age-related dementia affecting millions of people worldwide. This work aims at developing small, high-drug loading capacity (DL) and -entrapment efficiency (EE) memantine hydrochloride (MEM)/chitosan nanocrystals (CS-NCs) to treat moderate to severe dementia associated with AD. MEM-loaded chitosan nanocrystals (MEM/CS-NCs, further abbreviated as MEM-NCs) were prepared by the ionic gelation method. Different formulations were prepared by varying the concentrations of CS and sodium tripolyphosphate (STPP). The prepared MEM-NCs formulations (n = 8) were evaluated for their particle size (PS), polydispersibility index (PDI), zeta potential (ZP), DL, EE and characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, in vitro (i.e., release behavior, cytotoxicity) and ex vivo studies (i.e., histopathology) studies were carried out. The results show that the DL was over 92% and the EE was higher than 73%, while the particles were relatively small with nanometric PS (152.63 ± 12.95 to 310.23 ± 10.49 nm), uniform with acceptable PDI (0.336 ± 0.05 to 0.534 ± 0.02), and stable with positive ZP (23.8 ± 0.4 mV to 54.0 ± 0.5 mV). The optimal formulation (MEM-NC3) was selected mainly based on the PS (152.63 ± 12.95 nm), DL (98.44 ± 3.31%), and EE (78.7 ± 3.11%). Interestingly, it does not elicit any cytotoxic and tissue damage when examining at goat nasal mucosa. The selected formulation was subjected to surface morphological studies such as transmission electron microscopy (TEM), which revealed that the NCs were spherical in shape and small (100 nm). Interestingly, the selected formulation was able to sustain the drug release for up to 24 h with an initial burst release (86.51 %). We conclude that the prepared MEM-NCs represent a promising drug formulation for further in vivo studies (in animal models and in a clinical setting) to prevent and treat AD.

show abstract

Assessment and Validation of Globodera pallida as a Novel In Vivo Model for Studying Alzheimer’s Disease

Cited by 4 publications

References 78 publications

Ethnomedicinal Plants with Protective Effects against Beta-Amyloid Peptide (Aβ)1-42 Indicate Therapeutic Potential in a New In Vivo Model of Alzheimer’s Disease

Ethnomedicinal Plants with Protective Effects against Beta-Amyloid Peptide (Aβ)1-42 Indicate Therapeutic Potential in a New In Vivo Model of Alzheimer’s Disease

Neuroprotective effect of nose-to-brain delivery of Asiatic acid in solid lipid nanoparticles and its mechanisms against memory dysfunction induced by Amyloid Beta1-42 in mice

Preparation of Memantine-Loaded Chitosan Nanocrystals: In Vitro and Ex Vivo Toxicity Analysis

Contact Info

Product

Resources

About