Neuronal impulses in the brain are transmitted across synapses, which control brain function by facilitating the firing of neurons (excitatory synapses) or restricting it (inhibitory synapses). An imbalance in this process is thought to underlie several neurological diseases, including Alzheimer’s disease, mental retardation, autism, schizophrenia and epilepsy. Dr. Alaa El-Husseini was previously funded by MSFHR to support his research into the study of a post-synaptic density protein (PSD-95) that stimulates the formation and maturing of the synapses that release glutamate, a key neurotransmitter. He has also determined that this protein affects the balance of excitatory and inhibitory contacts induced by neuroligins, a family of cell adhesion molecules. Dr. El-Husseini’s current research focuses on how these proteins assemble at the synapse, uncovering the molecular mechanisms that govern the trafficking and function of these proteins to determine how their manipulation may affect synaptic balance.
Research Location: University of British Columbia - Point Grey
Reduction in microsporidian parasites
Microsporidia are a group of parasites that can only reproduce by invading and taking over an animal cell. They are highly dependent on their host cell for nutrients and energy, which has allowed them to discard genes for many metabolic proteins and evolve unique ways to carry out other essential activities. For example, microsporidian genomes are among the smallest of any complex cell. As the genomes shrink, critical information controlling gene expression has been squeezed from its conventional location. The mitochondria—known as the powerhouse of the cell—is also reduced nearly beyond recognition in form and function. In both these systems, the microsporidia do things differently from other cells, including the host animal cell in which they reside. Dr. Patrick Keeling is studying the effects of a shrunken genome and mitochondria in microsporidia, investigating how these reductions affect the way the parasite expresses its genes and targets proteins for function. Fully understanding these unique characteristics is important because, as with other parasites, such features could be exploited as targets for therapy.
Hormonal effects on neuroplasticity and behaviour
Contrary to popular belief, neurogenesis—the creation of new neurons—occurs in the adult brain in all species, including the human. Research demonstrates that hormones play a role in neurogenesis; however, research in this area is limited. Dr. Liisa Galea researches the means by which hormones regulate adult neurogenesis, influence mood, and contribute to learning and memory processes. Focusing specifically on estrogen and corticosterone, she is examining how hormonal changes during pregnancy affect the birth and survival of neurons, how stress alters these processes, and the links to behavioural changes such as depression. Determining the functional link between hormones and neurogenesis on learning, memory and depression may result in the development of hormonal therapeutic measures for promoting cognition, and new treatments to trigger neurogenesis in diseases characterized by lost brain tissue, such as Alzheimer’s and Parkinson’s.
Social class and health: Innovative theoretical exploration and empirical confirmation
Two broadly-defined approaches to conceptualizing social class can be applied to the empirical study of health inequalities. In the first, social class is equated with the socioeconomic status of individuals, i.e., with individual-level measures of wealth, educational credentials and/or occupational prestige. Explanations for empirical relationships between health and this particular conception of social class generally address material, behavioural or psychosocial phenomena, such as housing conditions, lifestyle choices or perceptions of relative standing. In the second, social classes are social groups, defined by the nature of their relationships to the economic mode of production and forms of control wielded in the workplace (the perspective of the neo-Marxist theorist Erik Olin Wright), or defined relationally in social space by their possession and utilization of various economic, educational, social and cultural capitals (the perspective of the French social theorist Pierre Bourdieu). In this tradition, explanations for class-health associations attempt to simultaneously address individual-level and group-level factors in a complex mix of agency and structure. Dr. Gerry Veenstra is investigating relationships between social class and health and well-being in Canada, integrating individual-level models founded upon material, lifestyle and psychosocial explanatory factors with social-structural theoretical frameworks inspired by theorists like Bourdieu and Wright. Building upon his previous work in BC, Dr. Veenstra will engage in an ethnographic exploration of different class positions and then administer a questionnaire survey to randomly-selected Canadian adults, assessing possession of various manifestations of control and capital. He will apply linear-causal statistical techniques such as regression analysis and relational techniques such as multiple correspondence analysis to this survey data in an attempt to identify and explain factors underlying social class and health inequalities in Canada.
The role of p53, p63 and p73 in the survival of oligodendrocytes following spinal cord injury
Spinal cord injury can be characterized into two broad pathological events known as the primary injury, typically a blunt force trauma, and the secondary injury, an ensuing degradation of both neurons and glial cells. The secondary injury is characterized by vascular alterations, poor blood flow, production of free radicals, oxidative stress, ionic imbalance, inflammation and excitotoxicity, which has a very large impact of the survival of oligodendrocytes, the cells responsible for myelination in central nervous system. These event occur days to weeks following the injury making them suitable for pharmacological intervention. Recent work has implicated p53 and p63 as pro-apoptotic (programed cell death) and p73 as antiapoptotic for neurons. Using animals which are absent of these factors specifically in oligodendrocytes, I wish to examine their affect on the survival and apoptosis of oligodendrocyte following a spinal cord injury. I also wish to correlate this difference in oligodendrocyte survival and apoptosis to the behavioural outcome of these animals. This will enable the validation of p53, p63, and p73 as targets to promote survival of oligodedrocytes following spinal cord injury. lf that is the case, it would suggest the need to develop novel treatments that target these proteins for potenetial future clinical application.
Prenatal Alcohol Exposure: Fetal programming, stress responsiveness, and vulnerability to depression and addiction
Women who consume large quantities of alcohol during their pregnancy can deliver babies with Fetal Alcohol Syndrome (FAS) or Alcohol Related Neurodevelopmental Disorder (ARND). Adults with FAS/ARND can exhibit a range of motor, behavioural and neurodevelopmental deficits. They also have higher rates of addiction and depression compared to the normal population. However, the relationship between prenatal exposure to alcohol and these psychiatric conditions is not known. One consequence of prenatal alcohol exposure (PAE) is re-programming of the neural system involved in stress, known as the hypothalamic-pituitary-adrenal (HPA) axis. Activation of the HPA axis during stressful situations is, in the short term, an adaptive response. But prolonged activation or an inability to “shut off” this system can have drastic consequences on brain function and behaviour. HPA dysfunction is implicated in the cause of depression, and activation of this system through stress can influence the initiation and maintenance of, as well as relapse to, drug addiction. Kim Hellemans is exploring how changes in the neural wiring of the HPA through PAE influences behaviours and neuroendocrine function associated with addiction and depression. Early targeting and prevention of psychiatric conditions is a critical goal of health research; the aim of Kim’s research is to determine whether normalizing HPA dysfunction in children with FAS/ARND can prevent their vulnerability to depression and addiction in adulthood.
The role of perfectionism, stress, and interpersonal discord in chronic headache disorders: A daily process study
Headache disorders are a prevalent health issue affecting between 10 to 35 per cent of the Canadian population. Headache disorders—which range from migraines to tension headaches—are associated with significant emotional, social and economic costs, including lost work days, decreased productivity and increased health care costs. There is increasing interest in understanding the role of psychosocial influences, such as personality traits, interpersonal interactions, coping and stress, in the onset, frequency and severity of headaches among sufferers. Perfectionism is a personality trait that has been identified as a potential risk factor for headache disorders. Perfectionists tend to experience greater stress due to their high expectations, self-critical tendencies and interpersonal conflict. Dayna Lee-Baggley is examining how perfectionism may generate and magnify risk factors (e.g., stress) for headache episodes. Her study is the first to monitor perfectionists’ experience of headaches on a daily basis. By identifying the risk factors associated with headache disorders, Dayna’s research will allow researchers to identify targets for intervention that could prevent or minimize the occurrence and impact of headaches for a substantial group of people.
Nuclear liver X receptors in the pathogenesis of, and the innate immunity against Samonella enterica
Salmonella enterica infections represent a serious public health problem. This bacterium causes diseases ranging from typhoid fever to food poisoning, affecting millions of people each year. Currently, there is little understanding of how Salmonella causes disease and the role of the immune system during the infection. The innate immune system is the first line of defense against pathogens, and is considered to be very important in defining the outcome of Salmonella infection. Recent evidences suggest that important components of the innate immune responses are modulated by some of the same elements involved in the control of various metabolic pathways. Previously, Alfredo Menendez was funded by MSFHR for his PhD research into the generation of a prophylactic vaccine against HIV-1. Now, Alfredo is studying the innate immune response against Salmonella, and the interplay between the control of inflammation and metabolism in the setting of Salmonella typhimurium infection, in vitro and in vivo. Research in this field may lead to the development of improved or novel treatments or vaccines for Salmonella through the enhancement of the innate immune response
Sensory function and dysfunction in neurotrauma: models, molecules and mechanisms
Spinal cord injury (SCI) interrupts the flow of information between the brain and spinal cord. As a result, people with SCI experience muscle paralysis. They also experience changes in sensation, ranging from a complete loss of sensation to chronic pain. Dr. Matt Ramer’s research focuses on the sensory nervous system and how its changes due to trauma related to sensory dysfunction. In particular, he is interested in the balance between factors that promote or inhibit the growth of nerve fibres (axons). Dr. Ramer is investigating the effects of growth-promoting and growth-inhibiting molecules on the anatomy of spinal sensory axons, on their connectivity within and outside the spinal cord, and on behavioural outcomes resulting from spinal cord injury. This work will increase our understanding of sensory dysfunction and may identify new therapies for SCI.
The effect of resistance training on cognitive performance, cortical plasticity, and fall risk in women aged 65 to 75 years old: A 12-month randomized controlled trial
Falling and fall-related injuries among the elderly is a significant health issue for seniors in Canada. Older adults with cognitive impairment are at particular risk; 60 per cent fall annually, a rate that is twice that of their peers with normal cognition. Previous research has demonstrated that current falls prevention programs, such as multifactorial interventions, are ineffective in people with cognitive impairment. This suggests the need for an innovative approach to falls prevention in this group, such as targeting cognitive function itself to reduce falls. As a two-time MSFHR Trainee, Dr. Teresa Liu-Ambrose researched the effectiveness of exercise and rehabilitation programs for preventing falls in women at risk, and the specific dimensions of cognition associated with falls risk in older women. Building on this research, Dr. Liu-Ambrose is now investigating whether resistance training — a mode of exercise proven to reduce the physiological risk of falls in older adults — also benefits cognition. In her study of cognitively-intact women aged 65 to 75, Dr. Liu-Ambrose is determining whether a 12-month resistance training program improves high-level cognitive function. Using standard neuropsychological tests and brain imaging techniques, she will measure changes in cognitive performance and cortical function. She will also evaluate changes in physiological falls risk. Results from this novel study will provide valuable insight into the development of falls prevention programs that specifically focus on cognitive function in older adults.