SYNAPTIC PROTEOME · Proteomics analysis of stress-induced synaptic plasticity

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Project objective

Stress is defined as any condition that seriously disturbs physiological and psychological homeostasis and is experienced by every individual throughout life. Exposure to stress can be either beneficial or disruptive in memory formation, and can on the long-term lead to serious neurological disorders.The aim of this project is to identify protein targets of stress-induced and glucocorticoid receptor-mediated memory formation and impairment. For this, I will investigate stress-induced memory formation or disruption and reveal molecular changes of the proteome at the synapses of the hippocampus, a key structure for cognition and memory formation. In particular, I will use a well-defined learning paradigm, contextual fear conditioning, for assessing hippocampus-dependent, stress-mediated learning and memory. I will couple this behavioural paradigm to state of the art proteomics studies of the synapse, i.e., 2D liquid chromatography (LC-LC) coupled to tandem mass spectrometry (MS-MS) in conjunction with iTRAQ la belling.This innovative approach is quantitative and can identify hundreds of proteins including membrane proteins, contained in up to four different samples (i.e., experimental conditions). In addition, we will use unique animal models, i.e., inbred and knock out mice, in order to gain a high discriminative power for identifying synaptic proteins that are relevant to the stress response. The outcome of my study will also be instrumental for addressing synaptic plasticity processes in other brain structure s related to stress-related psychopathologies, such as addiction or depression, in which synaptic plasticity changes might also be key processes in establishing pathological states.Taken together, this analysis will yield novel insight in the molecular mechanisms underlying stress effects, which is of scientific and social relevance. Moreover, this proposal will help me to discover a novel and career opportunity-rich field of proteomics research.

Original text from CORDIS.

Participants

• VRIJE UNIVERSITEIT AMSTERDAM · AMSTERDAMCoordinatorNetherlands

Links

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