Discussion

Spine morphology and synapse biology are key factors that determine neuronal function. Indeed many neurological disorders are caused by abnormalities of these important structures. Systematic and comprehensive quantification of spine and synapse morphology in relevant animal models and in efficacy studies will enable a better understanding of disease progression and support target validation.
To make such analyses possible we combine high-throughput microscopy with high-end automated image analysis using brain slices to enable an unbiased and comprehensive analysis. The robotics integrated in our workflow ensure that we can analyze large numbers of animals coming from different treatment groups or different cohorts from behavioural experiments.
We will present data on different transgenic models for neurological disorders, such as AD and HD. Disease-relevant read outs are used in both primary neuronal cultures as well as brain slices to establish in vitro-in vivo correlations during target validation or efficacy testing.
In combination with methodologies that allow target modulation in vivo, immunohistochemical endpoints followed by High Content Imaging become a powerful platform for target validation that allows following disease-relevant cellular events on ex vivo tissue samples.
Imaging biomarkers that determine sub-cellular events comprise a class of biomarkers that are in many cases translatable form animals to humans. The established platform may therefore find application also in pre-clinical studies.