The Use of Brain Slice Cultures for the Study of Epilepsy

Author(s):  
SCOTT M. THOMPSON ◽  
XIANG CAI ◽  
CÉLINE DINOCOURT ◽  
MICHAEL W. NESTOR

Author(s):  
Bianca Hutter-Schmid ◽  
Kathrin M. Kniewallner ◽  
Christian Humpel


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 592
Author(s):  
Cara L. Croft ◽  
Wendy Noble

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.



2006 ◽  
Vol 9 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Yoonsu Choi ◽  
Maxine A. McClain ◽  
Michelle C. LaPlaca ◽  
A. Bruno Frazier ◽  
Mark G. Allen






2007 ◽  
Vol 104 (2) ◽  
pp. 191-194 ◽  
Author(s):  
Ryuta Koyama ◽  
Rieko Muramatsu ◽  
Takuya Sasaki ◽  
Rie Kimura ◽  
Chihiro Ueyama ◽  
...  




2001 ◽  
Vol 80 (6) ◽  
pp. 349-355 ◽  
Author(s):  
Weiping Su ◽  
Aito Ueno-Yamanouchi ◽  
Koji Uetsuka ◽  
Hiroyuki Nakayama ◽  
Kunio Doi


Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 2067-2079 ◽  
Author(s):  
Fen Sun ◽  
Trinh Nguyen ◽  
Xin Jin ◽  
Renqi Huang ◽  
Zhenglan Chen ◽  
...  

Abstract Progesterone (P4) exerts robust cytoprotection in brain slice cultures (containing both neurons and glia), yet such protection is not as evident in neuron-enriched cultures, suggesting that glia may play an indispensable role in P4's neuroprotection. We previously reported that a membrane-associated P4 receptor, P4 receptor membrane component 1, mediates P4-induced brain-derived neurotrophic factor (BDNF) release from glia. Here, we sought to determine whether glia are required for P4's neuroprotection and whether glia's roles are mediated, at least partially, via releasing soluble factors to act on neighboring neurons. Our data demonstrate that P4 increased the level of mature BDNF (neuroprotective) while decreasing pro-BDNF (potentially neurotoxic) in the conditioned media (CMs) of cultured C6 astrocytes. We examined the effects of CMs derived from P4-treated astrocytes (P4-CMs) on 2 neuronal models: 1) all-trans retinoid acid-differentiated SH-SY5Y cells and 2) mouse primary hippocampal neurons. P4-CM increased synaptic marker expression and promoted neuronal survival against H2O2. These effects were attenuated by Y1036 (an inhibitor of neurotrophin receptor [tropomysin-related kinase] signaling), as well as tropomysin-related kinase B-IgG (a more specific inhibitor to block BDNF signaling), which pointed to BDNF as the key protective component within P4-CM. These findings suggest that P4 may exert its maximal protection by triggering a glia-neuron cross talk, in which P4 promotes mature BDNF release from glia to enhance synaptogenesis as well as survival of neurons. This recognition of the importance of glia in mediating P4's neuroprotection may also inform the design of effective therapeutic methods for treating diseases wherein neuronal death and/or synaptic deficits are noted.



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