The Role of Dopamine in Depression

Parkinsonā€™s disease (PD) is a progressive neurological disorder that typically begins with minor motor impairments and eventually progresses to severe immobility, as well as mood and cognitive dysfunction. About 40 per cent of patients experience major depression, marked by hopelessness, inability to experience pleasure, suicidal thoughts and delusions/hallucinations. While depression is an understandable reaction to living with a chronic and potentially debilitating illness, the rate of depression in PD patients is nearly double the rate of depression seen in comparably disabled patients with other chronic illnesses, indicating the likelihood of a neurochemical element. Common to this motor disorder and mood disorder is the neurochemical dopamine, a neurotransmitter that is involved in many brain activities, including movement and emotion. Elliott Bogusz is investigating the role of dopamine as it relates to depression in Parkinsonā€™s disease patients. He is identifying differences between depressed and non-depressed PD patients using Positron Emission Tomography (PET), a neuroimaging technology, to visualize dopamine activity in the brain. This research could provide insight into the development of Parkinsonā€™s disease and the neurochemical activity associated with depression. It also may contribute to the development of dopamine-related therapy in the treatment of depression and to screening depressed patients for Parkinsons.

Role of Notch-1 in Neurodegeneration and Neuroprotection

Alzheimer’s disease is a neurodegenerative disorder that causes deficits in memory, language and other cognitive functions. A family history increases the risk for Alzheimer’s by about four-fold. Early onset, familial Alzheimer’s disease (FAD) runs in families, and strikes under the age of 60. Brain cells shrink or disappear, and are replaced by irregularly shaped spots, called amyloid beta plaques (A-beta). A-beta is normally found in brain cells, but harmfully accumulates in FAD ā€“ a process that is facilitated by ā€œpresenilinā€ proteins. FAD has been linked to multiple genetic mutations, including defects in these proteins. These proteins also decrease the production of Notch-1, a brain receptor involved in learning and memory. Notch-1 is essential for normal development, but its role in the mature brain is unknown. Kelley Bromley is investigating the ability of Notch-1 to protect brain cells from the toxic effects of A-beta plaques, and how levels of Notch-1 change during the aging process. Her research could help explain how Alzheimerā€™s disease develops and potentially lead to new treatments for the condition.

Bereaved family caregivers’ adjustment to loss: developing evidence to support healthy adjustment

Providing care for someone with a life threatening illness is a difficult job that taxes family members’ emotional and physical resources. Changes in the health care system have increased the amount of care family caregivers provide at home, with the result that many are caring for a loved one seven days a week for weeks and months. About half of these family caregivers report chronic illnesses of their own, and up to a third have symptoms of depression. Painful emotions experienced by family caregivers can worsen when the ill person dies. Bereaved family caregivers suffer from exhaustion and emotional distress, and are at risk for developing health problems, including illness, insomnia, anxiety and depression. Even the most resilient people experience significant distress in the early months of bereavement. Health care providers do their best to respond to bereaved family caregivers’ needs, but little is known about what helps to foster adjustment in bereavement or when particular interventions would be most useful. Moira Cairns is asking bereaved family caregivers what they find helpful and unhelpful, with the goal of determining what types of care and support health professionals can offer to reduce physical, mental and social health risks and promote healthy adjustment among bereaved family caregivers.

Structure-function relationship in smooth muscle contraction

Hollow organs such as the intestines, bladder, uterus, blood vessels, and the airways that make up lungs are lined with smooth muscle cells. Normal functioning of these organs depends on the ability of these cells to contract and relax ā€“ processes that control the volume and shape of the organs and enable them to perform their various functions. When an individual has asthma, excessive contraction of the airway smooth muscle results in airway narrowing, compromising the individualā€™s ability to breathe. In asthmatics, airway smooth muscle has a tendency to generate more force and shorten more extensively than in individuals without asthma. This condition is further exacerbated by the fact that the muscle cells adapt to this shorter length, making it difficult for asthmatic airways to open after an attack has occurred. Leslie Chin is studying the role airway smooth muscle plays in the development of asthma. Generally, asthma research focuses on relaxing the smooth muscle cells which is typically accomplished by using an inhaler; however, it is also important to focus on preventing these muscle cells from adapting to shorter lengths. Leslie is investigating how this adaptation occurs in asthmatics and how this adaptation is prevented in healthy people. Understanding how both the mechanics of airway smooth muscle in asthma and the alterations are altered could lead to new treatments for the disease.

Seniors at high risk of falls: Clinical and economic studies

Falls among older people are a major health problem. In Canada, hospital emergency departments report that 86 per cent of seniorsā€™ injury-related admissions are due to falls, and individuals who present to an emergency department after one fall are at particularly high risk of falling again and incurring significant injuries. Current practice guidelines encourage a sophisticated and costly program to prevent subsequent (secondary) falls, including referrals to physiotherapy, ophthalmology, family practice and occupational therapy. However, despite the proven effectiveness of this approach, current ā€œreal lifeā€ practices throughout BC do not generally follow these guidelines, and the outcomes ā€“ both physical and economic ā€“ have not been studied in a Canadian context. Working within VGHā€™s Falls Prevention Clinic, Jennifer Davis is conducting the first Canadian randomized controlled trial to compare secondary falls and fall rate between seniors receiving ā€œgold standardā€ care at the Clinic versus those receiving the standard of care with their GP. She will also detail health resource utilization for all study participants in order to analyze the cost-effectiveness of the Clinic intervention versus the standard of care.

Characterization of the function of the nuclear matrix protein Lamin A in the organization of telomeres and chromosomes to determine the role in the pathology of Hutchinson-Gilford Progeria Syndrome

Hutchison-Gilford progeria syndrome (HGPS) is a rare, fatal disease that affects children and causes accelerated aging. Symptoms include dwarfism, loss of body fat and hair, aged-looking skin, stiff joints and hip dislocation. Children with this disease usually die of a heart attack or stroke at an average age of 13. HGPS is caused by a mutation in the LMNA gene which encodes a protein called Lamin A. The mutation causes instability in the cell nucleus, which is believed to lead to the premature aging in HGPS. Michelle Decker is looking for differences in the way normal and mutant versions of the Lamin A protein interact with chromosomes in the cell nucleus. Research has shown that cells from patients with HGPS have shorter than usual chromosome ends (called telomeres) than are usually found in cells of other children. Telomeres normally protect chromosomes from degradation and instability. By improving the understanding of the role that Lamin A and telomeres have in Hutchison-Gilford progeria syndrome, Michelleā€™s research may contribute to new understandings and therapies for the disease.

Role of Myosin Va in trafficking of neuronal vesicles

Neurons (brain cells) are separated by gaps called synapses and communicate via mechanisms which enable them to send and receive signals across these gaps. Inadequate development and maintenance of synapses is associated with a number of neurological and psychiatric conditions, from epilepsy to anxiety disorders, autism and mental retardation. Neurons use axons and dendrites to communicate across synapses. Axons are long fibers that transmit impulses to other neurons. Dendrites form a network of branches that receive signals from other nerve cells. Newly-made proteins within neurons must be transported to appropriate sites in axons or dendrites for proper communication to occur. However, little is known about how these proteins are accurately relocated. Frederick Dobie is studying one of the molecules thought to be involved in protein transport (Myosin Va), which is widespread in the brain, to clarify its role in pre and post-synaptic communication. Research has shown that a mutation in Myosin Va leads to Griscelli Syndrome, a disorder which causes severe motor and neurological impairment in humans. Other CNS disorders may also result from malfunctions in intracellular transportation of the proteins that facilitate communication between neurons. A better understanding of the action of transport molecules may lead to better methods of treatment for neurological disorders.

Meiotic errors in spermatogenesis: the role of recombination and synapsis in male-infertility and the production of aneuploid sperm

About two per cent of men are infertile due to defects in sperm production. In most cases, the underlying cause is unknown. During sperm production, two similar chromosomes ā€“ microscopic bodies that carry heredity DNA ā€“ pair up and exchange genetic material in a process called meiotic recombination. Recent studies have shown that recombination rates are significantly reduced in infertile men. Infertile men are also more likely to produce sperm with extra or missing chromosomes (called aneuploid sperm). This aneuploid abnormality is the most frequent cause of miscarriage, and among live births, the most common cause of congenital malformations. Kyle Ferguson is using leading edge technology to determine if and how aberrant recombination causes infertility. He is also investigating the recombination patterns that lead to production of aneuploid sperm. This information will help identify genetic mutations that contribute to male infertility, and may lead to new therapies for the condition.

The relationship between emotion processes and health in children at-risk for the development of anxiety disorders

While feeling shy, uncertain, or apprehensive with strangers or in new situations is common in young children, an excessive display of these behaviours can negatively affect day-to-day functioning. Disruptions in friendships and social activities, decreased school attendance and performance, and increased family conflict are all common consequences of extreme shyness. Research shows that children who consistently respond in these ways are more likely to develop anxiety disorders later in childhood and adolescence. Furthermore, older children and adults who display this pattern of behaviour have more general health complaints and problems. Sherri Frohlick is conducting a study aimed at understanding the development of these general health complaints by examining the ability of preschool-aged shy children to understand and express different emotions, and determining the effect of this on their health status. Just as being able to identify and communicate different emotions is an important part of healthy psychological growth, not having these skills is linked to emotional and behavioral problems such as depression, anxiety, aggression or other serious forms of psychological dysfunction. By examining emotion identification and communication as processes underlying health complaints and problems in young children, Sherri is working to develop prevention and intervention programs that identify their needs more directly and lessen health concerns. A reduction in health complaints would lessen the burden on a health care system faced with the challenge of diagnosing and treating these problems.

The role of dopamine in learning and memory in Caenorhabditis elegans

Dopamine is a chemical (neurotransmitter) that transmits signals between brain cells. Dopamine is involved in motor control, emotion, motivation, cognition, learning and memory. Fluctuations in the level of dopamine in the brain is associated with many conditions that involve deficits in learning and memory, including schizophrenia, Parkinsonā€™s disease, attention deficit-hyperactivity disorder (ADHD) and drug addiction. Andrew Giles is studying how dopamine acts to produce learning and memory in C.elegans, a microscopic worm with a nervous system similar to that of humans. Andrew is examining how changes in the levels of dopamine affect the completion of learning and memory tasks. This information will help explain how dopamine functions in human learning and memory, and its role in normal and abnormal behaviours. The results could support the development of new treatments for disorders involving memory and learning deficits.