Characterizing the development of neuroimmune proteins in the human primary visual cortex

Abstract

Neuroimmune proteins are involved in a wide array of biological functions throughout brain development. Importantly, these molecular mechanisms regulate the activity-dependent sculpting of neural circuits during the critical period. Abnormal expression of these molecular mechanisms, especially in early development, is linked to the emergence of neurodevelopmental disorders. Despite having central roles in both normal and pathological conditions, very little is known about the lifespan expression of neuroimmune proteins in the human cortex. As studies exploring the relationship between inflammation and disease tend to rely on animal models, unpacking immune lifespan trajectories in the human brain will be essential for translational research. Furthermore, it will aid the development of timely and effective therapeutic interventions for neurodevelopmental disorders. In my thesis, I characterize the development of 72 neuroimmune proteins in 30 postmortem tissue samples of the human primary visual cortex. These samples cover the lifespan from 20 days to 79 years. I compare the developmental profiles of these immune markers to those of well-studied classic neural proteins including glutamatergic, GABAergic and other synaptic plasticity-related markers. Using a data-driven approach, I found that the 72 neuroimmune proteins share approximately eight developmental patterns, most of which undulate across the lifespan. Furthermore, I used unsupervised hierarchical clustering to show that the development of neuroimmune proteins in the human visual cortex varies from that of classic neural proteins. These findings facilitate a deeper understanding of human cortical development through two classes of proteins involved in brain development and plasticity.