Haley Cook
Research Mentor(s): Bing Ye
Mentor Department: Life Sciences Institute, University of Michigan
Authors:
Session: Session 1 (9:00am – 9:50am)
Presentation Type: Poster 90
Abstract
Neuronal development is important for the proper assembly and function of the nervous system. Disruptions in this process can lead to neurological disorders. The Down syndrome cell adhesion molecule (DSCAM) gene, located on chromosome 21, is triplicated in individuals with Down syndrome. Overexpression of DSCAM results in abnormal axon terminal growth and excessive inhibitory GABAergic innervation, which has been linked to neurodevelopmental disorders. My current research shifts focus to the underexpression of DSCAM and its potential link to autism-related behaviors. Using DSCAM 2j mice, which carry an inactive form of the gene, my goal is to learn how reduced DSCAM levels impact neurogenesis and behavior, particularly in relation to autism spectrum disorders. Autism-related behaviors in DSCAM 2j mice include deficits in motor coordination, impaired working and spatial memory, and altered social recognition, mirroring features of autism spectrum disorders in humans. The effects of DSCAM underexpression will be examined through immunohistochemistry (IHC) staining of the dentate gyrus, the region of the brain where adult neurogenesis occurs. Staining will target antibodies such as nestin (a marker of neural progenitor cells), MCM2 (a marker of proliferative cells), and DAPI (to label nuclei), allowing for the quantification of neurogenesis and inhibitory neuron activity using confocal microscopy. Preliminary findings suggest that reduced DSCAM expression decreases inhibitory neuron activity in the dentate gyrus, potentially disrupting synaptic development and neurogenesis. The dentate gyrus regulates neurogenesis through a balance of excitatory and inhibitory inputs, and imbalances in this region may contribute to the behavioral abnormalities associated with autism spectrum disorders. By identifying the impact of DSCAM deficiency on neurogenesis and synaptic development, this research could inform targeted interventions to restore synaptic balance, offering potential therapeutic strategies for neurodevelopmental disorders linked to DSCAM dysregulation.
