Neurons Expressing Pathological Tau Protein Trigger Dramatic Changes in Microglial Morphology and Dynamics

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Microglial cells are key players in neuroinflammation and neurodegenerative diseases.
• Tauopathies are characterized by intraneuronal Tau aggregates, but microglial responses remain unclear.

Purpose of the Study:

• To investigate microglial cell behavior and function in vivo within a genetic zebrafish model of tauopathy.
• To elucidate the dynamic interactions between microglia and diseased neurons in real-time.

Main Methods:

• Utilized a genetic zebrafish model of tauopathy.
• Employed live imaging techniques to observe microglia behavior in vivo.
• Performed genetic ablation of microglia to assess their role in disease progression.

Main Results:

• In tauopathy, microglia exhibited increased motility and morphological changes (mobile cell bodies, shorter processes) compared to controls.
• Observed and quantified in vivo phagocytosis of apoptotic tauopathic neurons by microglia, with increased material uptake.
• Genetic ablation of microglia led to significantly increased Tau hyperphosphorylation.

Conclusions:

• Microglia dynamics and phagocytic activity are altered in the context of tauopathy.
• Microglia appear to provide a neuroprotective function in tauopathy by clearing diseased neurons.
• This study offers novel insights into real-time microglia-neuron interactions in neurodegenerative diseases.