Detailed information

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The information is provided in the language in which it was submitted by the researcher.

Project title:
Extrasynaptic NMDA receptors and resilience to chronic stress
Principal investigator(s):
Wong, Tak Pan
Co-investigator(s):
N/A
Supervisors:
N/A
Institution paid:
CIUSSS de l'Ouest-de-l'Ile-de-Montréal-Douglas Hospital
Research institution:
CIUSSS de l'Ouest-de-l'Ile-de-Montréal-Douglas Hospital
Department:
N/A
Program:
Project Grant - PA: Neurosciences, Mental Health and Addiction
Competition (year/month):
202109
Assigned peer review committee:
Molecular & Cellular Neurosciences - B
Primary institute:
Neurosciences, Mental Health and Addiction
Primary theme:
Biomedical
Term (yrs/mths):
1 yr 0 mth
CIHR contribution:
Contributors:
Amount:
$100,000
Equipment:
$0
External funding partner(s):
Partner Name:
N/A
Amount:
N/A
Equipment:
N/A
External applicant partner(s):
Partner Name:
N/A
Amount:
N/A
Equipment:
N/A
External in-kind partner(s):
Partner Name:
N/A
Amount:
N/A
Equipment:
N/A
Keywords:
Calcium Imaging; Chronic Social Defeat Stress; Depression; Electrophysiology; Glutamate; Hippocampus; Longitudinal Studies; Nanoparticle; Phosphorylation; Social Memory
Abstract/Summary:
Depression is a stress-related mood disorder that affects 300 million people worldwide. Considering that up to 30% of depressed patients are resistant to current treatments, the development of more effective antidepressants is warranted. N-methyl-D-aspartate receptor (NMDAR) could be an imperative therapeutic target for treating depression. Not only the expression of depression symptoms can be modeled by manipulating NMDAR function in animal studies, NMDAR antagonist such as ketamine has been used as a fast-acting antidepressant. In this project grant, we propose that a subpopulation of NMDARs that express outside synapses are crucial for enhancing our resistance to stress from developing depression. These so called extrasynaptic NMDARs can be specifically targeted by newly developed drugs in my laboratory for examining their roles in the vulnerability to stress and depression. In this project grant, we will use several animal models of chronic stress to test a hypothesis that enhancing extrasynaptic NMDAR function in a brain region called the hippocampus can increase our resilience to stress and ameliorate depression-related symptoms. We will examine molecular mechanisms that underlie pro-resilience effects of extrasynaptic NMDARs. The contribution of extrasynaptic NMDARs to the enhanced stress sensitivity in females will also be examined. Finally, we will focus on the effects of extrasynaptic NMDAR-targeting drugs on cognitive symptoms that are related to depression. Findings from this study could lead to the development of next generation of antidepressants for treating cognitive symptoms of depression. These antidepressants could also be used to reduce the vulnerability to depression in women.
Version:
20250311.1