Investigations into the neuroprotective actions of leptin in models of tau-related synaptic dysfunction.

Key pathological features of AD are accumulation of amyloid plaques and neurofibrillary tangles comprising hyper-phosphorylated tau. Synaptic impairments linked to amyloid are well established. However aberrant changes in tau also results in synaptic abnormalities and cognitive deficits in AD. Thus, limiting the aberrant effects of tau on synaptic function may prevent the synaptic abnormalities at pre-clinical stages of AD.

Metabolic dysfunction is a common feature in AD, and clinical studies have linked the metabolic hormone leptin to this disease, suggesting that leptin-based therapies may be beneficial in AD. Our recent studies support this as leptin prevents the aberrant effects of amyloid on synaptic function and neuronal viability in models of AD. But our understanding of the neuroprotective actions of leptin in tau-based models that mirror human AD pathology is limited.

This PhD studentship will use novel in vitro and in vivo models that replicate the tau-related synaptic dysfunction that occurs in AD. Electrophysiology combined with state of the art molecular and confocal imaging techniques will be used to monitor effects on hippocampal excitatory synaptic transmission and glutamate receptor trafficking in the tau-based models. This study will increase our understanding of tau-related synaptic deficits and provide further valuable information on therapeutic potential of leptin.

Apply
Please send your CV and two references to [Email Address Removed] by 14th January 2019.