Microglia are Activated in Neurodegenerative Diseases

Table of Contents

Abstract

Presentation

01. Introduction 02. Microglial Classification 03. Machine Learning Model 04. Activation Score 05. Alpha-Synuclein Mouse Model 06. Microglia Density 07. Microglia Activation 08. Activation vs. Density 09. Mouse Model Activation Score 10. Clustering 11. Summary

Microglia are activated in neurodegenerative
& neuroinflammatory diseases

Characteristics of microglia activation

Increased proliferation & density
Morphological changes
- Increase in soma size
- Alterations of processes
  - Fine & extended to short & dense
  - Spiky/hairy with thick processes

Multiple morphological features have been correlated with the degree of activation (Fernández-Arjona, 2019).

Resting microglia: extended with fine processes

https://opt003stagmediafiles.blob.core.windows.net/image/fa0dce1399c44a9bbbc647f39453088d

Activated microglia: spiky/hairy with thick processes

https://opt003stagmediafiles.blob.core.windows.net/image/51e77f8113984af3b76f34870f09016d

Proliferation

https://opt003stagmediafiles.blob.core.windows.net/image/bcd10e1277914bbd956b8a3d47cabb22

(images reproduced from Schwabenland et al., 2021; http://creativecommons.org/licenses/by/4.0)

References

Fernández-Arjona et al., Front. Cell. Neurosci., 13: 472, 2019; doi: 10.3389/fncel.2019.00472

Schwabenland et al., Acta. Neuropathol., 142: 923-936, 2021; doi: 10.1007/s00401-021-02370-8

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Microgliosis is implicated in most neurodegenerative and neuroinflammatory diseases. As part of the pathologic changes, microglia proliferate, migrate, and become activated. This process results in an overall increase in the Iba-1 protein density, which can be quantified using immunohistochemical (IHC) methods.

Microglial activation also results in characteristic morphological changes. The soma increases in size and the processes change from fine and extended, to short and dense, with an appearance that can sometimes be hairy or spiky. In addition, recent reports have correlated several morphological features with the degree of activation.

As such, in order to obtain the most sensitive measurement of microgliosis, we have developed a fully-automated microglial identification and characterization pipeline. In this presentation, we will show how this approach can provide sensitive metrics that are complementary to the Iba-1 staining density.