Heroes and Villains

What do a set of cells in the brain have in common with plumbers, gardeners, electricians, and morticians? These specialized dynamic cells are called glial cells. Michael Dailey at the University of Iowa focuses on working to understand the function of these cells in the brain. He makes the important point that more than ½ the cells in the brain are not neurons, they are glial cells. There are two types of glial cells, astrocytes and microglia cells. More specially, Dailey directs his attention to the microglia cells which are responsible for mediating immune responses, development, aging, and are highly motile. These cells can alter neuronal function, promote restoration of function, promote tissue repair, induce cell death, and recrute other immune cells. The distribution of these cells are uniform throughout the cortex. We know that these cells change dramatically in injured conditions. Through a process called phagocytosis, the branches of these cells will wrap themselves around a dead cell and ingest them. As mentioned previously, these cells have an important role in development. They act as plumbers when they are responsible for blood vessel formations, as gardeners when they induce apoptosis, electricians when they rewire neuronal circuits, and morticians when they remove dead cells. When there is neuronal injury, microglia is triggered and activated. This results in a change in microglia static. Activated cells serve as a hallmark of brain injury and disease. The form change these cells obtain can be helpful or harmful. If we can better understand the mechanisms through which these cells function, we may be able to control the harmful responses and enhance the helpful microglial responses. During development, these cells differ in developmental stages based on the timing, mode, and severity of the injury. For example, a harmful response the microglial cells exhibit include their responses to stoke. Neurons die during the absence of oxygen to the brain. The MG cells remain in an activated state. If we can figure out how to restrain MG cells to reduce proinflammatory factors we may be able to find better therapeutic approaches. In Dailey's approach to research, he studies the central nervous system tissue to study functional behaviors in microglia. The PS-P7 mouse is used which has not yet developed fully as a culture brain tissue is studied to see the changes that occur in tissue splicing. His findings include that within a few hours morphology of the cells after injury change from ramified to ameboid form. He works to understand how microglial responds to neural injury in developing brain tissues. Two relevant concerns discussed by Michael Dailey were effects of Alcohol exposure in utero. In studies mimicking fetal alcohol syndrome, researchers were able to inject alcohol and kill neurons located in the cortex. The Microglial cells respond strongly. The more alcohol exposure, the stronger microglial response is, resulting in more cell death in neurons. The microglial cells are shown to revert back with remarkable plasticity after the completion of their duties. In a Spectrum article titled “Brain’s immune cells may underlie autism risk from maternal infection” Zeliadt writes about researcher’s theory of microglial cells link between maternal infection and autism. In a study where they injected pregnant mice with a viral infection, the offspring showed behaviors reminiscent of children with autism such as a lacking of social interaction with other mice and repetitive behaviors. After 60 days, the brain slices of these offspring were analyzed and the microglial cells had increased amounts of interaction with dendritic spines, an excessive synaptic formation. In an attempt to use the information the researchers had gathered, they attempted microglial therapy in hopes of altering previous defects they had detected. The pups were given a drug, PLX5622 that is responsible for blocking a receptor necessary for microglial survival. These mice were given this drug at 21-42 days old. Most of the pup’s microglia is wiped out but by 60 days, they generate a new set of cells. These newly generated microglia differ from the original cells. Interesting findings included that the mice treated showed a significant decrease in social difficulties and the behavior of excessive grooming. The treatment was also able to normalize the density of dendritic spines. Although it is not entirely clear, the findings suggest that the loss of the abnormal original microglia is sufficient enough to to improve behavior of these mice. Their future research will focus on the effects of inhibition of growth factors produced by microglia and whether or not it would improve these characteristic autistic behaviors. References: https://www.spectrumnews.org/news/brains-immune-cells-may-underlie-autism-risk-maternal-infection/ https://loyolauniversitychicago-my.sharepoint.com/personal/rmorrison_luc_edu/_layouts/15/onedrive.aspx?slrid=1154899e%2Dd04b%2D6000%2D32be%2Df23ef814c311&FolderCTID=0x01200052F973E683B96F4F97B49148A837C07C&id=%2Fpersonal%2Frmorrison%5Fluc%5Fedu%2FDocuments%2FNEUR%20300%20%2D%20Fall%2018%2F%2810%2E30%2E18%29%20%2D%20Michael%20Dailey%2FEyo%5FDailey%5FJNIP%5F2013%2Epdf&parent=%2Fpersonal%2Frmorrison%5Fluc%5Fedu%2FDocuments%2FNEUR%20300%20%2D%20Fall%2018%2F%2810%2E30%2E18%29%20%2D%20Michael%20Dailey