P3-054: The amyloid-binding agent bta-eg4 reduces pathological tau species in a novel organotypic 3xTg-AD brain slice culture model that recapitulates key in vivo degenerative phenotypes

2015 ◽  
Vol 11 (7S_Part_14) ◽  
pp. P639-P639
Author(s):  
Cara L. Croft ◽  
Diane P. Hanger ◽  
Wendy Noble
Keyword(s):  
Brain Slice ◽  
Slice Culture ◽  
Binding Agent ◽  
Culture Model ◽  
Brain Slice Culture

scholarly journals Preparation of organotypic brain slice cultures for the study of Alzheimer’s disease

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 592
Author(s):  
Cara L. Croft ◽  
Wendy Noble
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Slice ◽  
Synaptic Dysfunction ◽  
Slice Culture ◽  
Therapeutic Effects ◽  
Culture Model ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures

Alzheimer's disease, the most common cause of dementia, is a progressive neurodegenerative disorder characterised by amyloid-beta deposits in extracellular plaques, intracellular neurofibrillary tangles of aggregated tau, synaptic dysfunction and neuronal death. There are no cures for AD and current medications only alleviate some disease symptoms. Transgenic rodent models to study Alzheimer’s mimic features of human disease such as age-dependent accumulation of abnormal beta-amyloid and tau, synaptic dysfunction, cognitive deficits and neurodegeneration. These models have proven vital for improving our understanding of the molecular mechanisms underlying AD and for identifying promising therapeutic approaches. However, modelling neurodegenerative disease in animals commonly involves aging animals until they develop harmful phenotypes, often coupled with invasive procedures. In vivo studies are also resource, labour, time and cost intensive. We have developed a novel organotypic brain slice culture model to study Alzheimer’ disease which brings the potential of substantially reducing the number of rodents used in dementia research from an estimated 20,000 per year. We obtain 36 brain slices from each mouse pup, considerably reducing the numbers of animals required to investigate multiple stages of disease. This tractable model also allows the opportunity to modulate multiple pathways in tissues from a single animal. We believe that this model will most benefit dementia researchers in the academic and drug discovery sectors. We validated the slice culture model against aged mice, showing that the molecular phenotype closely mimics that displayed in vivo, albeit in an accelerated timescale. We showed beneficial outcomes following treatment of slices with agents previously shown to have therapeutic effects in vivo, and we also identified new mechanisms of action of other compounds. Thus, organotypic brain slice cultures from transgenic mouse models expressing Alzheimer’s disease-related genes may provide a valid and sensitive replacement for in vivo studies that do not involve behavioural analysis.

scholarly journals An Ex Vivo Brain Slice Culture Model of Chronic Wasting Disease: Implications for Disease Pathogenesis and Therapeutic Development

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Naveen Kondru ◽  
Sireesha Manne ◽  
Robyn Kokemuller ◽  
Justin Greenlee ◽  
M. Heather West Greenlee ◽  
...  
Keyword(s):  
Brain Slice ◽  
Chronic Wasting Disease ◽  
Ex Vivo ◽  
Slice Culture ◽  
Wasting Disease ◽  
Disease Pathogenesis ◽  
Culture Model ◽  
Therapeutic Development ◽  
Brain Slice Culture

A brain slice culture model for studies of endogenous and exogenous precursor cell migration in the rostral migratory stream

2009 ◽  
Vol 1295 ◽  
pp. 1-12 ◽  
Author(s):  
Mette Tanvig ◽  
Morten Blaabjerg ◽  
Rikke K. Andersen ◽  
Ana Villa ◽  
Ann Mari Rosager ◽  
...  
Keyword(s):  
Cell Migration ◽  
Brain Slice ◽  
Rostral Migratory Stream ◽  
Precursor Cell ◽  
Slice Culture ◽  
Culture Model ◽  
Brain Slice Culture ◽  
Migratory Stream

scholarly journals Preparation of organotypic brain slice cultures for the study of Alzheimer’s disease

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 592 ◽  
Author(s):  
Cara L. Croft ◽  
Wendy Noble
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Slice ◽  
Synaptic Dysfunction ◽  
Slice Culture ◽  
Therapeutic Effects ◽  
Culture Model ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures

Alzheimer's disease, the most common cause of dementia, is a progressive neurodegenerative disorder characterised by amyloid-beta deposits in extracellular plaques, intracellular neurofibrillary tangles of aggregated tau, synaptic dysfunction and neuronal death. Transgenic rodent models to study Alzheimer’s mimic features of human disease such as age-dependent accumulation of abnormal beta-amyloid and tau, synaptic dysfunction, cognitive deficits and neurodegeneration. These models have proven vital for improving our understanding of the molecular mechanisms underlying AD and for identifying promising therapeutic approaches. However, modelling neurodegenerative disease in animals commonly involves aging animals until they develop harmful phenotypes, often coupled with invasive procedures. We have developed a novel organotypic brain slice culture model to study Alzheimer’s disease using 3xTg-AD mice which brings the potential of substantially reducing the number of rodents used in dementia research from an estimated 20,000 per year. Using a McIllwain tissue chopper, we obtain 36 x 350 micron slices from each P8-P9 mouse pup for culture between 2 weeks and 6 months on semi-permeable 0.4 micron pore membranes, considerably reducing the numbers of animals required to investigate multiple stages of disease. This tractable model also allows the opportunity to modulate multiple pathways in tissues from a single animal. We believe that this model will most benefit dementia researchers in the academic and drug discovery sectors. We validated the slice culture model against aged mice, showing that the molecular phenotype closely mimics that displayed in vivo, albeit in an accelerated timescale. We showed beneficial outcomes following treatment of slices with agents previously shown to have therapeutic effects in vivo, and we also identified new mechanisms of action of other compounds. Thus, organotypic brain slice cultures from transgenic mouse models expressing Alzheimer’s disease-related genes may provide a valid and sensitive replacement for in vivo studies that do not involve behavioural analysis.

Brain tumor invasion model system using organotypic brain-slice culture as an alternative to in vivo model

2002 ◽  
Vol 128 (9) ◽  
pp. 469-476 ◽  
Author(s):  
Shin Jung ◽  
Hyun-Woo Kim ◽  
Je-Hyuk Lee ◽  
Sam-Suk Kang ◽  
Hyang-Hwa Rhu ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Invasion ◽  
Brain Slice ◽  
Model System ◽  
In Vivo Model ◽  
Slice Culture ◽  
Invasion Model ◽  
Organotypic Brain Slice ◽  
Brain Slice Culture

scholarly journals Modeling α-Synucleinopathy in Organotypic Brain Slice Culture with Preformed α-Synuclein Amyloid Fibrils

2020 ◽  
Vol 10 (4) ◽  
pp. 1397-1410
Author(s):  
Amandine Roux ◽  
Xinhe Wang ◽  
Katelyn Becker ◽  
Jiyan Ma
Keyword(s):  
Brain Slice ◽  
Amyloid Fibrils ◽  
Three Dimensional ◽  
Brain Slices ◽  
Alpha Synuclein ◽  
Slice Culture ◽  
Suitable Model ◽  
Organotypic Brain Slice ◽  
Brain Slice Culture

Background: Synucleinopathy is a group of neurodegenerative disorders characterized by neurodegeneration and accumulation of alpha-synuclein (α-syn) aggregates in various brain regions. The detailed mechanism of α-syn-caused neurotoxicity remains obscure, which is partly due to the lack of a suitable model that retains the in vivo three-dimensional cellular network and allows a convenient dissection of the neurotoxic pathways. Recent studies revealed that the pre-formed recombinant α-syn amyloid fibrils (PFFs) induce a robust accumulation of pathogenic α-syn species in cultured cells and animals. Objective: Our goal is to determine whether PFFs are able to induce the pathogenic α-syn accumulation and neurotoxicity in organotypic brain slice culture, an ex vivo system that retains the in vivo three-dimensional cell-cell connections. Methods/Results: Adding PFFs to cultured wild-type rat or mouse brain slices induced a time-dependent accumulation of pathogenic α-syn species, which was indicated by α-syn phosphorylated at serine 129 (pα-syn). The PFF-induced pα-syn was abolished in brain slices prepared from α-syn null mice, suggesting that the pα-syn is from the phosphorylation of endogenous α-syn. Human PFFs also induced pα-syn in brain slices prepared from mice expressing human α-syn on a mouse α-syn-null background. Furthermore, the synaptophysin immunoreactivity was inversely associated with pα-syn accumulation and an increase of neuronal loss was detected. Conclusion: PFF-treatment of brain slices is able to induce key pathological features of synucleinopathy: pα-syn accumulation and neurotoxicity. This model will be useful for investigating the neurotoxic mechanism and evaluating efficacy of therapeutic approaches.

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