Complement System Activation Peptide C5a Regulates Cell Polarity

A protein usually associated with the immune system could play a role in the development of neurological conditions such as epilepsy and schizophrenia, University of Queensland researchers say.

Dr. Liam Coulthard led the study into how brain development is affected by altering the activity of the complement system – which controls innate immunity – during pregnancy. The study showed the protein occurs in significant amounts in brain regions during development in utero, prior to the immune system being developed.

The complement system was also activated in a human model of brain development using induced pluripotent stem cells, in work done in collaboration with Professor Ernst Wolvetang from UQ’s Australian Institute for Bioengineering and Nanotechnology.

Essential Complement Factor

Dr Coulthard said:

“Our research in mouse models has shown neural defects can result when this system is functioning inappropriately in utero. We blocked a key complement component, called C5a, for three days during pregnancy, and this resulted in behavioral abnormalities in the offspring. Our research demonstrates this complement factor is essential for the proper development of the brain and has a broader role in addition to its function in the immune system.”

C5a has been linked to inflammation pathways in neurodegenerative conditions such as motor neuron disease, and the lab is working towards the development of new drugs to block disease progression.

“Our findings confirm that drugs inhibiting this system could pose a risk in pregnancy and could prompt recommendations they not be given to women of child-bearing age,” Dr Coulthard said. “Any development of drugs for this target to treat pregnancy-related inflammatory diseases such as pre-eclampsia should be approached with caution.”

Support for the work came from the ARC Centre of Excellence and the National Health and Medical Research Council.

Liam G. Coulthard, Owen A. Hawksworth, Rui Li, Anushree Balachandran, John D. Lee, Farshid Sepehrband, Nyoman Kurniawan, Angela Jeanes, David G. Simmons, Ernst Wolvetang, Trent M. Woodruff
Complement C5aR1 Signaling Promotes Polarization and Proliferation of Embryonic Neural Progenitor Cells through PKCζ
Journal of Neuroscience 28 April 2017, 0525-17; DOI: 10.1523/JNEUROSCI.0525-17.2017

Image: University of Queensland

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