Date of Graduation
Eberly College of Arts and Sciences
Individuals at risk for developing Alzheimer's disease (AD) often demonstrate hyperactivity in areas of the memory network, such as the hippocampus, prior to AD diagnosis. Evidence suggests that this hyperactivity might be a contributing factor to the development of AD. Tau, a protein responsible for binding and maintaining microtubules, has been implicated as a factor in hyperactivity, potentially through its alterations in glutamate signaling. Glutamate, the primary excitatory neurotransmitter in the central nervous system, is essential for learning and memory. However, excess glutamate that accumulates in the synapse can lead to neuron loss and eventual behavioral impairments. Recently, our lab has found that a tau mouse model of AD (rTg(TauP301L)4510) exhibits an increase in glutamate release and a decrease in glutamate clearance, effects that are correlated with memory deficits. We hypothesized that regulating glutamate levels would attenuate the spatial memory deficits observed in TauP301L mice. To test this, we administered riluzole, an FDA-approved disease-modifying drug for the treatment of amyotrophic lateral sclerosis, which decreases glutamate release and increases glutamate uptake. TauP301L mice exhibited memory deficits in the 8-arm water radial arm maze (WRAM), and administration of riluzole attenuated these deficits. Our findings establish a potential therapeutic intervention for memory deficits caused by glutamate dysregulation.
Weitzner, Daniel S., "Attenuation of Spatial Memory Impairment in a Tau Mouse Model of Alzheimer's Disease with Riluzole" (2015). Graduate Theses, Dissertations, and Problem Reports. 6935.