Accelerating Research: IHN's Dr. Wilson's Recent Grant Award

Dr. Tony W. Wilson was recently awarded a new R01 grant from the National Institute on Drug Abuse (NIDA), an arm of the National Institutes of Health. The project, “Coupling of Inflammasome Cascades and Aberrant Neural Oscillatory Dynamics in NeuroHIV,” investigates the role of proteins called inflammasomes and their impact on brain activity in persons living with HIV.

When Your Body Betrays Itself

Your body’s immune system naturally produces inflammasomes as a defense against infection. This defense kicks in when a pathogen (bacteria, virus, etc.) is detected. Once detected, the body releases chemical cues that initiate programmed cell death as a way to eliminate the infection resulting in systemic inflammation. This strategy is intended to stop pathogens from replicating in the body. When this process is in check, other chemical cues are then released, deactivating inflammasomes and the programmed cell death, returning things to normal.

However, pathogens like HIV can significantly alter the overall function of the immune system and may block this deactivation signal, leading to a state of chronic systemic inflammation. Meaning the inflammation already affecting the entire body is heading toward developing into an autoimmune disease or inflammatory disease. Such persistently high inflammatory levels are thought to contribute to an increased chance of comorbidities (a.k.a., the presence of multiple medical conditions) in people living with HIV, including a greater risk of a condition affecting the brain. One such condition can include a noticeable decline in brain function such as memory, attention, reasoning and decision making among others.

Your Brain and Body Working Together

One way that scientists at IHN are learning more about how continued inflammation might lead to complications in brain function is by looking at neural oscillations. Neural oscillations occur when neurons – the cells in the brain that send information or signals to other neurons – band together in larger groups called networks. When this happens, they send the same signal together in a rhythm. This synchronized rhythmic firing is referred to as a neural oscillation. This process occurs throughout the brain and is a foundational feature of brain function.

Chronic systemic inflammation has been shown to impact how well these networks of neurons are able to synchronize with each other, resulting in a higher risk of developing cognitive impairment. Such impairments include:

-          Decreased accuracy in working memory

-          Slower attention

-          Decreased reasoning

-          Slower decision making

Scientists at IHN are still in the process of discovering how, when and where neural oscillations are impacted by inflammation. Additionally, relief from such inflammation in people with HIV remains limited. Increasing evidence suggests that the anti-inflammatory properties of cannabis may have some therapeutic potential in this area. However, the benefit remains poorly understood and the impact that regular cannabis use has on these neural networks and brain function more generally remains unknown.

This project seeks to answer the following questions:

1)      What are the common and specific inflammasome activation and deactivation triggers that are altered in the context of HIV infection and cannabis?

2)      How much of an impact do inflammasomes have on persistent inflammation and brain function?

3)      Does long-term cannabis use affect inflammasome function and overall inflammatory levels in people with HIV and, if so, what is the impact on brain function in this population?

4)      Does long-term cannabis use have a neutralizing or negative impact on brain activity and function in people living with HIV.

Through this project, Dr. Wilson and colleagues aim to expand the field’s understanding of how inflammasomes contribute to the persistently high inflammatory levels observed in people with HIV and determine whether long-term cannabis use modulates such inflammation and thereby has a positive or negative impact on brain and cognitive function. The long-term goal of this research is to advance the development of therapeutic options for neurological comorbidities in people living with HIV and other conditions where persistently high inflammatory levels are thought to play a major role. Currently, the therapeutics options for such condition are very limited.