The Brain Research Group led by Dr. Isabelle Aubert at Sunnybrook Research Institute is developing new ways to treat Alzheimer’s disease.
A typical pathological feature of a person with Alzheimer’s disease is the accumulation of toxic amyloid-beta in the brain. In this short movie, lab members Emmanuel Thévenot and Jessica Jordão describe the use of a software from Imaris to evaluate the volume of a brain cell found in proximity to amyloid-beta deposits, called plaques.
Studying the volume of brain cells in relationship to amyloid plaques can lead to a better understanding of disease progression in, and treatment alternatives for, Alzheimer’s.
Alzheimer’s disease is the most common form of dementia. It is characterized by pathological hallmarks, such as the deposit of amyloid-beta peptides (Aβ) and neuronal loss. Cholinergic neurons, containing the enzyme choline acetyltransferase (ChAT) and able to synthesize the neurotransmitter acetylcholine, are among the neurons that degenerate in Alzheimer’s disease. Acetylcholine is a key player in cognitive function; as the disease progresses, cholinergic neurons deteriorate, ChAT levels decrease and the amount of acetylcholine present in the brain becomes insufficient for the maintenance of adequate learning and memory functions.
To stimulate brain repair, prevent further degeneration and improve cognitive functions, we are developing novel approaches to be able to do the following:
- Noninvasively deliver therapeutic molecules, including anti-amyloid agents, genes and stem cells to the brain
- Promote neuronal survival, axonal growth and adult neurogenesis
- Stimulate ChAT activity and the production of acetylcholine
Dr. Kullervo Hynynen, director of imaging research at Sunnybrook Research Institute, and Dr. JoAnne McLaurin are close collaborators on projects related to the noninvasive delivery of anti-amyloid agents to the brain.
Projects
Alzheimer’s disease (AD) is characterized by the deterioration of neurons in the brain.
When healthy, neurons may fulfil a variety of roles ranging from the control of movement to cognitive function. Cholinergic neurons that release the neurotransmitter acetylcholine and mediate such functions as learning and memory are one of the groups of neurons that decline substantially in AD. Enhancing the communication between neurons and improving other functions of neurotransmitters have been the primary therapeutic foci, but these solutions are often insufficient in the case of severe neuronal degradation.
Our research aims to develop a better understanding of the processes involved in the decline of patients with AD and to uncover novel approaches to treatment of the disease through the following projects:
Brain development, degeneration and regeneration group projects
Our goal is to develop a multicomponent therapeutic strategy to halt the toxicity of amyloid-beta peptides, to promote neuronal survival and regeneration, and to improve cognitive function. We are using gene and stem cell therapies, anti-amyloid-beta approaches, and novel methods to deliver therapeutic agents noninvasively to the brain.
This project is funded by the Canadian Institutes of Health Research and the Ontario Mental Health Foundation.
Evidence suggests that certain cell adhesion molecules regulate the development and function of cholinergic neurons; this project will assess these functions in three main parts. To begin, we will assess the importance of specific cell adhesion molecules in the development and maturation of cholinergic neurons. Then, we will elucidate whether the direct stimulation of given receptors by these cell adhesion molecules results in an increase in the activity of cholinergic neurons. Finally, we will elucidate intracellular signaling mechanisms through which these cell adhesion molecules control the function of cholinergic neurons.
These studies are important to the basic understanding of cholinergic neuronal development, which requires a complex orchestration of cellular and molecular interactions to produce characteristics specific to this type of neuron. Furthermore, the knowledge obtained on
developing cholinergic neurons may translates into strategies to promote cell survival, axonal growth and maturation for regenerating cholinergic neurons in the adult and aging brain.
This research is funded by the Natural Sciences and Engineering Research Council.
Facilities
The laboratory of the brain repair group is equipped for commonly used cellular, molecular, biochemical and surgical approaches.
We use specialized equipment in the lab, including a stereology system (StereoInvestigator, MBF Bioscience, Inc).
We also use the following core facilities at Sunnybrook Research Institute (SRI):
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Centre for Flow Cytometry and Microscopy
Houses a Nikon A1 laser scanning confocal microscope and equipment for cell sorting and analysis
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Histology
A fully equipped lab that offers processing, embedding, sectioning and routine staining
Scientist
Laboratory manager
Kelly Markham-Coultes: kcoultes@sri.utoronto.ca
PhD candidates
Sonam Dubey
Jessica Jordão: jfjordao@sri.utoronto.ca
Ewelina Maliszewska-Cyna: ewelina@sri.utoronto.ca
Paul Nagy: pnagy@sri.utoronto.ca
MSc candidate
Tiffany Scarcelli: tiffany.scarcelli@sri.utoronto.ca
Danielle Weber-Adrian
Middle: Emmanuel Thévenot, Lillian Weng, Kelly Markham-Coultes, Stephanie Bell
Bottom: Yanbo Guo, Isabelle Aubert, Tiffany Scarcelli, Kristiana Xhima