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With more than 600 identified neurological diseases and an aging population, research is under way to understand the underlying causes and possible cures for these often devastating disorders. Neurodegenerative disorders include Alzheimer’s Disease, ALS, Huntington’s Disease, Multiple Sclerosis, and Parkinson’s Disease.  Recent research also points to the role of neuroinflammation and neuroimmune response in prevalent neurological diseases, and studies have shown that changes in cytokines, lymphocytes, and some epigenetic mechanisms affect CNS processes and can be associated with reduced cognitive abilities and occurrence of several neurodegenerative diseases.

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See what you’re missing – RNA expression like you've never seen it before

Neurodegenerative diseases are complex.  Understanding the molecular mechanisms of Neurological disease development and progression is key to identifying potential therapeutic targets, through biomarker analysis as well as protein localization and gene expression.  RNAscope® in situ hybridization (ISH) technology enables cell- and tissue-specific localization of RNA transcripts quickly and precisely for functionally important targets in the nervous system.  

Furthermore, dual IHC and ISH techniques enable detailed evaluation of the expression and localization of both proteins and genes in intact tissue sections, where natural anatomical features are preserved.  Download the following application notes for more information and examples about how ACD Bio can help accelerate your discoveries so you can publish faster.

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Get access to the ACD Bio Application Notes

app notes

  • Detection of RNA in the central and peripheral nervous system using the RNAscope® in situ hybridization assay
  • Specific Detection of RNA Expression and Distribution in Brain Using RNAscope® Technology 
  • Insights on Dual ISH-IHC 
Fill in the below for to access the ACD Bio Application Notes

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Metabolic Dysfunction as an Indicator of Disease

Mitochondria play central roles in meeting the demands of neuronal synapses for energy (ATP). Mitochondrial dysfunction results in impaired neuroplasticity, neuronal degeneration and cell death, and is now recognized as a key element in neurodegenerative diseases, including Alzheimer’s and Huntington’s diseases, Dementia with Lewy bodies, and Parkinson’s disease. The development of model assay systems such as primary neurons, isolated brain mitochondria and pre-synaptic nerve terminals (synpaptosomes) from specific brain regions have enabled identification of mitochondrial defects associated with neurodegenerative diseases.

The Seahorse XF Analyzer has been shown to handle small sample sizes to monitor mitochondrial respiratory parameters of synaptosomes using 50-fold less protein than previously possible.

A recent announcement by La Trobe University described an exciting step forward in the possibilities of early diagnosis of Parkinson’s Disease. 

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Through the bioenergetic analysis of blood cells, this test will enable the detection of abnormal metabolism in the blood cells in people with Parkinson's, opening up the possibility of early treatment for the disease.   Key to this research was the Seahorse Extracellular Flux Analyser, used to analyse the bioenergetic phenotype of cells, and which may be used to identify similar mitochondrial disfunctions in other neurodegenerative conditions such as Huntington’s and Alzheimers disease. 

Other Resources:

Agilent Technologies application note here:
https://www.agilent.com/cs/library/applications/appnote-primary-neuronal-difficiencies.pdf
Learn more about Agilent Technologies (Seahorse Bioscience) here:
https://lifescience.invitro.com.au/brands/agilent-technologies-seahorse-bioscience/

Label Free time course analysis of neuronal cell behaviour

Neuronal apoptosis and necrosis occur in a large number of neurodegernative diseases.  Even though progress has been made in understanding the principles of cell death signaling in neurons, time course analyses of neuronal cell death had proved to be difficult to achieve.  The xCELLigence System of Real-Time Cell Analyzers developed by ACEA Biosciences enables a non-invasive and label-free way to continuously monitor cellular behavior, and has been utilized to determine the response of neurons to different cell death stimuli, to monitor neuroprotection, and to enable high-throughput screening of anti-Alzheimer’s disease drugs amongst other applications.

Other Resources:

Download the ACEA Neurotoxicity Application note here:
http://www.aceabio.com/wp-content/uploads/Neurotoxicity-Real-Time-Detection-of-Neuronal-Cell-Death-by-Impedance-Based-Analysis.pdf

Learn more about this technology in the following publication by Huo etal: A novel assay for high-throughput screening of anti-Alzheimer's disease drugs to determine their efficacy by real-time monitoring of changes in PC12 cell proliferation.
http://www.ncbi.nlm.nih.gov/pubmed/24378397

Learn more about ACEA Bioscience here:
https://lifescience.invitro.com.au/brands/acea-biosciences/

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Whole tissue imaging – explore structure and function relationships with X-Clarity

Results utilizing the CLARITY technique have uncovered the 3-D architecture of Alzheimer’s Disease lesions and enabled the study of the distribution of Alzheimer’s disease pathology in 3-D, even in post-mortem human tissue.  Logos Biosystems have further developed the CLARITY technology to make significant improvements for tissue clearing speed, efficiency, and reproducibility.  The X-CLARITY™ Tissue Clearing System from Logos Biosystems is an all-in-one, easy-to-use solution for electrophoretic tissue clearing. Its unique design accelerates the removal of lipids from tissues in a highly efficient manner, producing structurally sound and transparent whole tissues ready for multiple rounds of antibody labeling and imaging. Moreover, the X-CLARITY™ Tissue Clearing System successfully produces transparent tissues that are efficiently penetrated by and labeled with macromolecules such as antibodies or oligonucleotides. This allows for the 3D imaging of large tissues at single-cell resolution.  The method has opened up a world of possibilities, from tracing neural circuitry to exploring the relationship between structure and function. 

The X-CLARITY™ Tissue Clearing System can clear a whole mouse brain in just 6 hours, an astounding 8 times faster than the original technology.

x clarity demo

Other Resources:

View this publication describing how the Clarity technique has been used to visualise senile plaques, neurofibrillary tangles and axons in 3-D in an Alzheimers brain.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131133/

See how the X-Clarity has been used recently in this Nature biomedical engineering publication enabling a better 3D model of pathology specimens with a view to enabling better assessment of treatment options for cancer diagnosis. 
https://www.nature.com/articles/s41551-017-0084?error=cookies_not_supported&code=167260a1-0ade-4b80-b349-22bba91959e4

Learn more about the Logos X Clarity here  
https://lifescience.invitro.com.au/core-facilities/imaging/tissue-clearing/