White blood cells involved in brain development after birth

The young brain is incredibly malleable, and it undergoes changes every day from birth until adulthood. These numerous changes are crucial for shaping the brain so that it functions properly. However, errors in this development process have been linked to juvenile mental health disorders, including depression, bipolar disorder, and schizophrenia. Knowing more about what is happening at the cellular level during these changes could help us understand and treat these conditions, as well as other neurodevelopmental disorders.  

In a new preclinical study published in iScience, PhD candidate Micaël Carrier (pictured; Tremblay Lab) and his co-authors used models to discover the previously unexpected role of white blood cells in the brain development of newborns. They found that these cells, which typically circulate in blood vessels, were able to enter the brain during the two first weeks of life and remove unwanted connections between neurons, called synapses.

The removal of certain synapses is a healthy developmental process. (In this study, the white blood cells eliminated synapses releasing glutamate, the main excitatory messenger in the brain.) During early development, neurons make a lot more connections than needed later in life, so removing these connections once they’ve served their purpose increases the efficiency of our brain. Retaining too many synapses is also something seen in some conditions like autism spectrum disorder and schizophrenia.

To understand the role of white blood cells, Micaël and his co-authors in the Tremblay Lab investigated the cells’ dynamic in the brain and blood using three complementary microscopy and molecular techniques. The research showed that both the number and the structure of the white blood cells in the brain changed throughout time. In the second week of life, the white blood cells had an appearance resembling microglia, the brain’s resident immune cells. As microglia play a major role in brain maturation and synaptic pruning, this suggests that white blood cells might act as their helpers in this essential but enormous endeavour. 

Molecular tests confirmed that the white blood cells in the brain also expressed many proteins that they do not typically express while in the blood. This told Micaël and his team that these cells are highly dynamic, and they can adapt their protein expressions depending on their environment and the role they need to accomplish.

Overall, Micaël and his co-authors in the Tremblay lab highlighted the possible implication of white blood cells in mental health by discovering their contribution to brain development. As white blood cells are easy to investigate and manipulate thanks to their presence in the blood, this could open new possibilities for mental health therapeutics that work by leveraging these cells.

This study counted on the participation of many Tremblay Lab members, including first-author Micaël, a PhD candidate from Laval University and a visiting researcher at UVic; Fernando González Ibáñez, a PhD candidate from Laval University and a visiting researcher at UVic; Dr. Haley A. Vecchiarelli, a postdoctoral fellow in the Tremblay Lab; Elisa Gonçalves de Andrade, who recently obtained her Master’s degree from UVic under the supervision of Dr. Marie-Ève Tremblay; and Drs. Marie-Kim St-Pierre and Katherine Picard, who recently obtained their PhDs from Laval University under the supervision of Dr. Marie-Ève Tremblay.