CEST Imaging Combined with 1H-MRS Reveal the Neuroprotective Effects of Riluzole by Improving Neurotransmitter Imbalances in 3xTg AD Mice

Motivation: Glutamate (Glu) and gamma-aminobutyric acid (GABA) imbalance plays a significant role in Alzheimer's disease (AD) pathogenesis. Whether riluzole can improve neurotransmitter homeostasis in AD brain remains unclear. Goal(s): Using CEST imaging and 1H-MRS to monitor Glu/GABA changes in riluzole-treated AD mice and evaluate riluzole's efficacy and mechanism. Approach: Measured Glu/GABA levels using GluCEST, GABACEST, and 1H-MRS in riluzole-treated 3xTg AD mice. Assessed cognition brain pathology, neuronal survival, and protein expression. Results: Riluzole increased GluCEST/GABACEST signals, elevated Glu/GABA levels in AD mice, correlating with improved cognition. Riluzole reduced AD-related pathology, increased neuronal survival, and restored Glu/GABA-related protein expression. Impact: This study highlights the potential of combining CEST imaging and 1H-MRS as a non-invasive approach to evaluate riluzole's effects on Glu/GABA metabolism and cognitive function in AD mice, providing a promising neuroimaging tool for assessing AD therapies.