The Djavad Mowafaghian Centre for Brain Health Kickstart Grants are intended to encourage research that demonstrates new collaborations, directions, and technological developments. They support new projects that generate preliminary data for future grant applications to external funding agencies.
Congratulations to the DMCBH researchers and their teams who have received this year’s Kickstart Grants!
Shernaz Bamji and Jacqueline Quandt: Validating ZDHHC9 as a therapeutic target for Multiple Sclerosis
Multiple sclerosis (MS) is characterized by both damage to the myelin sheath (demyelination) and a failure to repair the damaged myelin (remyelination). The objective of this study is to determine whether the palmitoylating enzyme, ZDHHC9, can promote oligodendrocyte differentiation and whether this process can be controlled to improve outcomes for patients with MS.
Oligodendrocyte differentiation is the process where oligodendrocyte precursor cells (OPCs) mature into oligodendrocytes and play an important role in the formation and maintenance of myelin. In MS patients, there is insufficient remyelination due to disruptions in the ability of OPCs to differentiate. The research team hypothesizes that ZDHHC9 can help OPCs mature into fully functioning oligodendrocytes and thereby help with the repair of damaged myelin.
By understanding the mechanisms involved in this process, the research team hopes to develop new strategies and therapies for treating MS.
Annie Ciernia, Sheila Teves and Seth Parker: The role of metabolic driven changes in histone lactylation in regulating microglial inflammation
Microglia are the resident immune cell of the central nervous system (CNS). During infection, microglia respond through complex metabolic, transcriptional and epigenomic changes that result in inflammation.
Preliminary findings suggest that inflammation triggers a metabolic change in microglia, leading to increased lactate levels and specific modifications of histones that influence the genes involved in microglial responses to inflammation. However, it is still unclear how this metabolic shift leads to different modifications in specific genomic locations. Understanding this mechanism could help develop new treatments for neuroinflammatory diseases. The research team plans to study how the metabolic changes in microglia are linked to different histone modifications and how these changes affect microglial functions in diseases like Alzheimer’s.
Thalia Field and Jill Zwicker: Assessing long-term trajectories of brain structure, neurodevelopment and function in adolescents with complex congenital heart disease
Medical advancements have greatly improved the survival rates of individuals with congenital heart disease (CHD). As a result, there are now more adults living with CHD than children with the disease, making it a rapidly growing field in cardiology. However, there is still a need to understand the long-term health effects of CHD, especially on brain health and cognitive function.
Studies have revealed that newborns with CHD show abnormalities in brain development and are associated with an increased risk of brain injuries after birth. These early brain injuries are linked to motor and neurodevelopmental problems during infancy and early childhood. Adults with CHD also have a higher risk of dementia, stroke and other neurological issues.
To better understand these issues, researchers will examine longitudinal changes in brain maturation, injury and associated functional performance in a group of individuals who were born with complex CHD and are now in late childhood and early adolescence.
Deborah Giaschi, Alexander Weber, Hee Yeon Im, Tamara Vanderwal and Miriam Spering: New magnetic resonance approaches to understanding developmental visual disorders
Amblyopia and dyslexia are two common developmental disorders that affect the brain. Despite their differences, both disorders involve difficulties with motion perception, face perception, reading and attention.
The goal of this project is to understand how the dorsal and ventral visual streams contribute to visual problems in children with amblyopia or dyslexia. The research team wants to identify the neural correlates of motion perception, face perception, and attention, as well as the functional connectivity between the dorsal and ventral regions of the brain and networks involved in reading and attention.
This project has two main aims. First, researchers want to establish functional magnetic resonance imaging (fMRI) protocols that involve watching movies instead of traditional tasks to better understand real-life relevance and generalizability of the findings. Second, they aim to develop new magnetic resonance-based methods for measuring cortical excitation and inhibition in children by using magnetic resonance spectroscopy (MRS) to measure changes in the levels of neurotransmitters.
Jason Snyder and Manu Madhav: Experience-specific tuning of postnatally-born hippocampal neurons
Neural circuits in the brain develop and change based on our experiences to help us adapt and behave in different situations. This is seen in sensory systems like our vision, where experience drives the formation of eye-specific circuits during critical periods in our early years. However, not much is known about how specific experiences shape the development of circuits in other brain regions, like the hippocampus.
Compared to sensory areas, the hippocampus develops slowly and continues to develop even into adulthood. One specific area called the hippocampal dentate gyrus (DG), is the last region to develop, and new neurons are continuously generated there throughout life. These newly generated neurons go through critical periods where their development is influenced by experiences. Surprisingly, very little is known about how these neurons develop and function, especially the ones born soon after birth, even though they make up about half of the population of DG neurons. The research team believes that these developmentally-born DG neurons become specialized to respond to environmental cues during adolescence, which then helps enhance learning and memory later in life.