The oDGal Mouse: A Novel, Physiologically Relevant Rodent Model of Sporadic Alzheimer’s Disease

Chadwick, Wayne; Maudsley, Stuart; Hull, William M.; Havolli, Enes; Boshoff, Eugene; Hill, M. J.; Goetghebeur, Pascal Jd; Harrison, David C.; Nizami, Sohaib; Bedford, David C.; Coope, Gareth; Real, Katia; Thiemermann, Christoph; Maycox, Peter R.; Carlton, Mark; Cole, Sarah L.

doi:10.3390/ijms24086953

Cited by 5 publications

(3 citation statements)

References 102 publications

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“…The concentration of donepezil in the emulsion and in the aqueous solution was 450 μg/mL. Donepezil is used as a positive control (acetylcholinesterase inhibitor) at a dosage of 1–5 mg/kg of body weight in models of memory impairment in rodents. , In our study, we used a medium value of the dosage (3 mg per kg of body weight).…”

Section: Methodsmentioning

confidence: 99%

Anti-Alzheimer Drug Delivery via Pickering Emulsions Stabilized by Plate-like Cellulose Nanocrystals

Mikhaylov,

Torlopov,

Vaseneva

et al. 2023

Langmuir

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In this work, we studied for the first time the formation of olive oil emulsions in water stabilized by plate-like nanocrystals with the supramolecular structure of cellulose II (pCNC). Effects of storage, pCNC concentration, and NaCl on the stability and properties of Pickering emulsions, including the creaming index, droplet size, zeta potential, acid−base surface properties, and rheology, were studied. A significant influence of the shape of nanoparticles (compared to the classical rod-like shape) on the stability parameters and rheological characteristics of emulsions is shown. Plate-like cellulose nanocrystals at a concentration of 16 g/L are able to form delamination-resistant emulsions without added electrolytes. The viscosity of pCNC-stabilized emulsions tends to decrease with increasing electrolyte concentration in the system, which is not characteristic of rod-like CNC-stabilized emulsions. This effect in pCNC-stabilized emulsions assumedly can be associated both with weak mechanical engagement between drops due to the shape of stabilizer particles and with an insignificant participation of background electrolyte cations in the formation of interdroplet interactions. Therefore, the resulting aggregates are unstable and easily destroyed, even under weak mechanical stress. As a consequence, the acid−base properties of the pCNC surface are practically independent of the emulsion preparation method (with or without electrolyte) as well as the concentration of the background electrolyte. The reduced viscosity of pCNC-stabilized emulsions in the presence of an electrolyte, coupled with the absence of acute toxicity, allows us to recommend them as a convenient oral delivery system for fatsoluble, biologically active substances. Our emulsions carrying donepezil (an anti-Alzheimer drug) showed better performance than a solution of donepezil hydrochloride in preventing memory impairment tested on laboratory mice.

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Section: Methodsmentioning

confidence: 99%

Anti-Alzheimer Drug Delivery via Pickering Emulsions Stabilized by Plate-like Cellulose Nanocrystals

Mikhaylov,

Torlopov,

Vaseneva

et al. 2023

Langmuir

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“…This decline in glucose metabolism occurs progressively, worsening over time. Decrease in CMRglu can lead to neuronal death and cognitive decline [ 76 , 77 ]. While the exact reason for this hypometabolism is not well understood, it may be related to the accumulation of amyloid plaques and neurofibrillary tangles [ 78 ].…”

Section: Hypometabolism In Admentioning

confidence: 99%

Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An Overview

Raut

Bhalerao

Powers

et al. 2023

Cells

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The brain is a highly dynamic organ that requires a constant energy source to function normally. This energy is mostly supplied by glucose, a simple sugar that serves as the brain’s principal fuel source. Glucose transport across the blood–brain barrier (BBB) is primarily controlled via sodium-independent facilitated glucose transport, such as by glucose transporter 1 (GLUT1) and 3 (GLUT3). However, other glucose transporters, including GLUT4 and the sodium-dependent transporters SGLT1 and SGLT6, have been reported in vitro and in vivo. When the BBB endothelial layer is crossed, neurons and astrocytes can absorb the glucose using their GLUT1 and GLUT3 transporters. Glucose then enters the glycolytic pathway and is metabolized into adenosine triphosphate (ATP), which supplies the energy to support cellular functions. The transport and metabolism of glucose in the brain are impacted by several medical conditions, which can cause neurological and neuropsychiatric symptoms. Alzheimer’s disease (AD), Parkinson’s disease (PD), epilepsy, traumatic brain injury (TBI), schizophrenia, etc., are a few of the most prevalent disorders, characterized by a decline in brain metabolism or hypometabolism early in the course of the disease. Indeed, AD is considered a metabolic disorder related to decreased brain glucose metabolism, involving brain insulin resistance and age-dependent mitochondrial dysfunction. Although the conventional view is that reduced cerebral metabolism is an effect of neuronal loss and consequent brain atrophy, a growing body of evidence points to the opposite, where hypometabolism is prodromal or at least precedes the onset of brain atrophy and the manifestation of clinical symptoms. The underlying processes responsible for these glucose transport and metabolic abnormalities are complicated and remain poorly understood. This review article provides a comprehensive overview of the current understanding of hypometabolism in AD and potential therapeutic targets.

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“…This approach is useful because it enables the analysis of both prodromal and symptomatic sAD by changing the doses, which establishes the required pathology and enables to study its impact on several cognitive areas. As the model is easy and affordable it can be used to study sporadic AD pathologies and develop its therapeutics [ 126 ].…”

Section: Main Textmentioning

confidence: 99%

Insight into the emerging and common experimental in-vivo models of Alzheimer’s disease

Dhapola,

Kumari,

Sharma

et al. 2023

Lab Anim Res

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Alzheimer’s disease (AD) is a multifactorial, rapidly progressing neurodegenerative disorder. As the exact cause of the disease is still unclear, the drug development is very challenging. This review encompasses the commonly used AD models involving various chemicals, heavy metals and endogenous substances induced models and the transgenic models. It also provides insight into the reliable emerging models of AD that may overcome the shortcomings associated with available models. Chemicals like streptozotocin, scopolamine, colchicine and okadaic acid render the animal susceptible to neuroinflammation and oxidative stress induced neurodegeneration along with amyloid-β deposition and tau hyperphosphorylation. Similarly, endogenous substances like acrolein and amyloid-β 1–42 are efficient in inducing the major pathologies of AD. Heavy metals like aluminum and fluoride and mixture of these have been reported to induce neurotoxicity therefore are used as animal models for AD. Transgenic models developed as a result of knock-in or knock-out of certain genes associated with AD including PDAPP, APP23, Tg2576, APP/PS1, 3 × Tg and 5 × FAD have also been incorporated in this study. Further, emerging and advanced pathomimetic models of AD are provided particular interest here which will add on to the current knowledge of animal models and may aid in the drug development process and deepen our understanding related to AD pathogenesis. These newly discovered models include oAβ25-35 model, transgenic model expressing 82-kDa ChAT, oDGal mouse and APP knock-in rat. This study may aid in the selection of suitable model for development of novel potent therapeutics and for exploring detailed pathogenic mechanism of AD. Graphical abstract

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The oDGal Mouse: A Novel, Physiologically Relevant Rodent Model of Sporadic Alzheimer’s Disease

Cited by 5 publications

References 102 publications

Anti-Alzheimer Drug Delivery via Pickering Emulsions Stabilized by Plate-like Cellulose Nanocrystals

Anti-Alzheimer Drug Delivery via Pickering Emulsions Stabilized by Plate-like Cellulose Nanocrystals

Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An Overview

Insight into the emerging and common experimental in-vivo models of Alzheimer’s disease

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