Ex vivo therapy of malignant melanomas transplanted into organotypic brain slice cultures using inhibitors of histone deacetylases

2006 ◽  
Vol 112 (2) ◽  
pp. 205-215 ◽  
Author(s):  
Annett Hölsken ◽  
Ilker Y. Eyüpoglu ◽  
Mike Lueders ◽  
Christian Tränkle ◽  
Detlef Dieckmann ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Brain Slice ◽  
Ex Vivo ◽  
Malignant Melanomas ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures

scholarly journals Organotypic brain slice cultures to model neurodegenerative proteinopathies

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
C. L. Croft ◽  
H. S. Futch ◽  
B. D. Moore ◽  
T. E. Golde
Keyword(s):  
Neurodegenerative Disorders ◽  
Brain Slice ◽  
Ex Vivo ◽  
Three Dimensional Model ◽  
Ex Vivo Model ◽  
Initial Development ◽  
Neuroscience Research ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures

AbstractOrganotypic slice cultures of brain or spinal cord have been a longstanding tool in neuroscience research but their utility for understanding Alzheimer’s disease (AD) and other neurodegenerative proteinopathies has only recently begun to be evaluated. Organotypic brain slice cultures (BSCs) represent a physiologically relevant three-dimensional model of the brain. BSCs support all the central nervous system (CNS) cell types and can be produced from brain areas involved in neurodegenerative disease. BSCs can be used to better understand the induction and significance of proteinopathies underlying the development and progression of AD and other neurodegenerative disorders, and in the future may serve as bridging technologies between cell culture and in vivo experiments for the development and evaluation of novel therapeutic targets and strategies. We review the initial development and general use of BSCs in neuroscience research and highlight the advantages of these cultures as an ex vivo model. Subsequently we focus on i) BSC-based modeling of AD and other neurodegenerative proteinopathies ii) use of BSCs to understand mechanisms underlying these diseases and iii) how BSCs can serve as tools to screen for suitable therapeutics prior to in vivo investigations. Finally, we will examine i) open questions regarding the use of such cultures and ii) how emerging technologies such as recombinant adeno-associated viruses (rAAV) may be combined with these models to advance translational research relevant to neurodegenerative disorders.

Organotypic Brain Slices of ADULT Transgenic Mice: A Tool to Study Alzheimer’s Disease

2019 ◽  
Vol 16 (2) ◽  
pp. 172-181
Author(s):  
Christian Humpel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Brain Slice ◽  
Ex Vivo ◽  
Brain Slices ◽  
Adult Mice ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures ◽  
Organotypic Brain Slices

Transgenic mice have been extensively used to study the Alzheimer pathology. In order to reduce, refine and replace (3Rs) the number of animals, ex vivo cultures are used and optimized. Organotypic brain slices are the most potent ex vivo slice culture models, keeping the 3-dimensional structure of the brain and being closest to the in vivo situation. Organotypic brain slice cultures have been used for many decades but were mainly prepared from postnatal (day 8-10) old rats or mice. More recent work (including our lab) now aims to culture organotypic brain slices from adult mice including transgenic mice. Especially in Alzheimer´s disease research, brain slices from adult transgenic mice will be useful to study beta-amyloid plaques, tau pathology and glial activation. This review will summarize the studies using organotypic brain slice cultures from adult mice to mimic Alzheimer's disease and will highlight advantages and also pitfalls using this technique.

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.

Alpha-Synuclein is Involved in Manganese-Induced ER Stress via PERK Signal Pathway in Organotypic Brain Slice Cultures

2013 ◽  
Vol 49 (1) ◽  
pp. 399-412 ◽  
Author(s):  
Bin Xu ◽  
Fei Wang ◽  
Sheng-Wen Wu ◽  
Yu Deng ◽  
Wei Liu ◽  
...  
Keyword(s):  
Er Stress ◽  
Brain Slice ◽  
Alpha Synuclein ◽  
Signal Pathway ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures

scholarly journals A Bridge Between in vitro and in vivo Studies in Neuroscience: Organotypic Brain Slice Cultures

2020 ◽  
Author(s):  
Merve Alaylioglu ◽  
Erdinc Dursun ◽  
Selma Yilmazer ◽  
Duygu Gezen-Ak
Keyword(s):  
Brain Slice ◽  
In Vivo Studies ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures

Organotypic Brain Slice Cultures

2018 ◽  
Vol 123 (1) ◽  
pp. e59 ◽  
Author(s):  
Christian Humpel
Keyword(s):  
Brain Slice ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures
Sign in / Sign up

Export Citation Format

Share Document