Abstract #2259

Retrograde Neuronal Injury in Response to Glutaric Acid in Glutaric Acidemia Type 1 (GA-1) Mouse Model

Jelena Lazovic¹, William J. Zinnanti², Xiaowei Zhang³, Russell Jacobs³

¹Radiology, University of California, Los Angeles, Los Angeles, CA, United States; ²Neurology, Stanford, Palo Alto, CA, United States; ³California Institute of Technology

The aim of this work was to investigate whether local increases in glutaric acid, a metabolite that accumulates in glutaric academia type 1 (GA-1), can lead to retrograde neuronal injury. In this metabolic disorder, the striatum appears to be highly vulnerable brain region, without apparent high glutaric acid content. We hypothesized that increase in glutaric acid levels in areas outside the striatum can cause distal striatal injury. The addition of glutaric acid to the thalamus, induced neuronal injury in the substantia nigra, while cortical injection of glutaric acid resulted in localized striatal injury.