UC San Diego

Short term brain injuries such as ischemic stroke and concussions have been identified as risk factors for the long-term development of neurodegenerative pathologies such as Alzheimer’s Disease and chronic traumatic encephalopathy. These brain injuries are known to trigger a substantial release of glutamate, an excitatory neurotransmitter, into the synaptic cleft between neurons. The highly concentrated extracellular glutamate repeatedly activates post-synaptic receptors and induces an influx of cations into the post-synaptic neuron. This influx triggers a disruption of normal neuronal morphology and cytoskeletal structure, which may potentiate cell death. We observe that dendritic microtubule dynamics are rapidly disrupted by repetitive rapid glutamate receptor activation, and the disruption is negatively correlated to previously described aberrant F-actin reorganization. We also observe that neurons exposed to a transient excitotoxic stress can recover certain cytoskeletal features following an extended period of recovery, but may develop pathological microtubule-associated-protein tau aggregates that are associated with the aforementioned long term neurodegenerative pathologies. This suggests that transient excitotoxic glutamate stress may be a link between traumatic brain injuries and the development of long term neurodegenerative disease.