Neuronal Stress and Its Hormetic Aspects

Abstract Neurons are highly adaptable cells that need to respond distinctly to a variety of signals. These signals often act as stressors and show a biphasic dose response, as it has been described as a conceptual basis for hormesis. One such stressor is the neurotransmitter glutamate, which plays a pivotal role in synaptic transmission. The frequency of stimulation and the dose of glutamate can lead to distinct adaptive responses that are able to alter the efficacy of the synapse—a process called synaptic plasticity. Long-term depression, a weakening of the synapse due to low-frequency stimulation and low doses of glutamate, as well as long-term potentiation, a strengthening of the synapse due to high-frequency stimulation and moderate doses of glutamate, are physiological processes and are beneficial for brain function. In contrast, excessive stimulation and high levels of glutamate are toxic to neurons. This pathological mechanism is termed excitotoxicity.