Poster abstracts
Poster number 61 submitted by Bryan Alvarez
Developing a Novel AAV for Synaptic Plasticity: CRMP3-/- Reduces Synaptic Elements, Dendritic Spine Maturity, PGC-1α, and Disrupts Mitochondrial Biogenesis in the Hippocampus
Bryan Alvarez (Institute for Behavioral Medicine Research, The Ohio State University, Neuroscience Graduate Program, The Ohio State University), Lauren Taylo (Institute for Behavioral Medicine Research, The Ohio State University), Sabrina Mackey-Alfonso (Institute for Behavioral Medicine Research, The Ohio State University), Emmanuel Scaria (Institute for Behavioral Medicine Research, The Ohio State University), Jade A. Blackwell (Institute for Behavioral Medicine Research, The Ohio State University), Tam T. Quach (Department of Physiology and Cell Biology, The Ohio State University)
Abstract:
Many neurodegenerative diseases affecting cognition begin with synaptic plasticity impairments in the hippocampus. Collapsin response mediator proteins (CRMPs) play various roles in synaptic plasticity, dendritic outgrowth, and mitochondrial morphology and motility in neurons. Mitochondrial dysfunction is known to contribute to synaptic plasticity impairments. In neonates, CRMP3 deletion (CRMP3-/-) has been shown to result in dystrophic hippocampal dendrites, abnormal spine morphogenesis, and impairments in long-term potentiation (LTP). Although CRMP3 is expressed throughout the nervous system during development, it is predominantly expressed in the hippocampus in adulthood. CRMP3’s role in dendritic morphology and cognitive behaviors throughout adulthood is not yet well understood. We have previously shown that CRMP3-/- mice display generalized freezing during contextual fear conditioning, a hippocampus-dependent task. To characterize the role of CRMP3 in adulthood, we explored various synaptic mitochondrial regulatory elements within the hippocampus from early to late adulthood. Additionally, we quantified dendritic morphology in the CA1 region using Golgi-Cox staining and machine learning analysis. We show that CRMP3-/- reduces pre-synaptic, post-synaptic, and mitochondrial regulatory elements, as well as dendritic spine maturity, within the hippocampus in both male and female CRMP3-/- mice. Moving forward, we aim to utilize an adeno-associated virus (AAV) for the overexpression of CRMP3 as a potential therapeutic approach for neurodegenerative diseases affecting synaptic plasticity and mitochondrial function, such as Post-Operative Cognitive Dysfunction.
Keywords: Synaptic Plasticity, Mitochondrial Funtion, Aging