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Neurosciences & Mental Health

Announcements

Zhengping Jia received $826,200 from CIHR for his project "Targeting specific domains of AMPA glutamate receptors in synaptic and cognitive impairments in Alzheimer's disease"

Project description: Alzheimer's disease (AD) is the leading cause of dementia and imposes enormous social and financial burden on affected individuals and our society, but no effective treatment or cure is currently available. A hallmark pathology of AD is the accumulation of amyloid plaques in the brain mainly composed of amyloid peptides, but how these peptides lead to neuronal loss and cognitive impairments remains unclear. Recent studies indicate that AD begins with changes at the synapse, the key site of neuronal communication and plasticity, and that synaptic deficits are the best correlates of cognitive impairments. Therefore, elucidating how amyloid peptides cause synaptic and cognitive dysfunction is essential for the understanding and treatment of the disease. The overall objective of this project is to unravel the molecular mechanisms by which amyloid peptides cause synaptic and memory deficits. We will focus on AMPA receptors (AMPARs) because they are the principal mediator of excitatory synaptic transmission and are critical for synaptic plasticity widely accepted as the cellular basis for memory formation. We have developed several superior mouse models with changes in specific subunits and regions of AMPARs and shown that these mice are differentially altered in different forms of synaptic plasticity as well as in synaptic impairments induced by amyloid peptides. These results lead to a hypothesis that different subunits/regions of AMPARs differentially contribute to synaptic and cognitive impairments in AD. We will use a multidisciplinary approach and a combination of cutting-edge techniques to address this hypothesis. This project will reveal novel molecular mechanisms by which amyloid peptides cause neuronal and cognitive deficits in AD and provide highly specific therapeutic targets to treat this devastating disease.

Steven Miller received 910,352 from CIHR for his project "Healthy brain growth in preterm children for optimal function: do males and females differ?"

Project description: In Canada and around the world, babies born too early (preterm) are at high risk of brain injuries that lead to developmental disabilities. Newborn brain injury was once considered a single event with fixed consequences. Our work is changing how we think about brain injury in preterm babies. We discovered that brain injury influences how the brain grows, and that the consequences of newborn brain injury change over time and vary from child to child. We showed that routine "everyday" events experienced by hospitalized sick newborns, like pain from life-saving procedures and medications, may affect patterns of brain growth as well as motor, thinking and language skills across childhood. We have identified everyday clinical practices for sick preterm newborns and social factors that foster their early motor, thinking and language development as toddlers. Yet, we do not know if those changes in brain and development differ in girls and boys, or how the changes affect their school-age functions and behavior. Given these gaps in our understanding, we propose to answer the key question posed by parents of preterm children every day: How do I give my child every chance for her/his best future outcome? We have studied a unique group of babies born very preterm using detailed measures of infant brain growth, clinical factors during neonatal intensive care, and early motor, thinking and language development. We now propose to assess how brain growth and children's functions and behavior at 4.5 and 8 years of age differ in girls and boys. By studying children from birth to age 8, we will: 1. Determine how the relationship between newborn brain injury and brain growth to age 8 years is modified by the child's sex. 2. Determine how the child's sex modifies the link between brain growth and thinking skills and behavior at age 8 years. 3. Develop better ways to predict school-age function (e.g. thinking, language) using knowledge of the child's sex and her/his brain development.

Karen Gordon received $559,980 from CIHR for her project "Novel treatment to establish spatial hearing in children who are deaf"

Project description: Over 1 in 1000 children have permanent hearing loss and need early treatment and therapy to help them develop speech and language. We showed that many children hear better with two rather than one hearing device but that they still have a very hard time listening. Normally, the auditory system combines information from our two ears together seamlessly to help us hear each sound around us and to know where each sound is coming from. This "spatial" hearing is very important because this is how we sense the world in all directions around us and how we pick out and focus on one sound at a time to listen to. The problem is that children with hearing loss are not developing spatial hearing properly. We want to fix this by making sure that two hearing aids or two cochlear implants work well together like two normal hearing ears do. We use responses from the auditory brainstem to tell us when sound from both ears is best matched and then reset the devices to send sound in this new way for >100 children with hearing loss (>50 using two hearing aids and >50 using two cochlear implants). We ask each child to use the new device settings for 12 months. After the first 6 months, we measure changes in responses from the auditory system and the children's ability to hear from both ears. Sound localization therapy in half of the group begins at this time. After 12 months, we test whether children can better hear where sound is located and better understand spoken words in a noisy room. We also do the same tests in >100 similar children with hearing loss and >50 children with normal hearing so that we know how well the treatments have worked and how close these children with hearing loss have come to listening normally. We are known around the world for showing that it is important to give children hearing in both ears. We now have to correct the gaps in present treatment so that they can make the best use of their hearing devices to develop the spatial hearing they need.

Steve Prescott received $2.87 million for his research on neuron hyperexcitability and chronic pain

Following a nerve injury, many neurons generate too many spikes in response to sensory input, which distorts how sensory input is perceived and often results in chronic pain. His study aims to explore changes in gene regulation to decipher how and why injured neurons respond to treatments with compensatory changes that undermine the beneficial effects of pain medications. The study will also explore how changes in the excitability of different types of neurons affect the pattern of neurons activated by stimuli, and how changes in neuron activation patterns ultimately impact a patient’s perception of pain. The goal is to use the research to identify the underlying pattern of hyperexcitability to help determine the best therapeutic options for patients.