The effects of high fat diet on adult neurogenesis in the brainstem

Postnatal neurogenesis is known to occur in specific niches of the brain, such as the hippocampus and subventricular zone, which enables production of new interneurones to be integrated into neuronal circuits. There is also evidence for neurogenesis in other brain areas, such as the spinal cord (1) and brainstem, which is critical for metabolic homeostatic control. This region contains the dorsal vagal complex (DVC), which senses insulin levels and subsequently stimulates changes in feeding behaviour and glucose metabolism, through activation of neuronal circuits. In high fat diet, insulin resistance occurs in the DVC, through increased mitochondrial fission (2) and this leads to changes in the responsiveness of this region however, little is known about whether high fat diet changes the levels of neurogenesis in this region or indeed whether inflammatory responses involve production of immune cells in the region.
This project will study how high fat diet may affect neurogenesis in this and other regions and the mechanisms that underlie changes. It will also examine whether high fat diet induced changes may be modulated by activation of specific neurotransmitter systems and the mechanisms underlying these changes. We will use disease models of obesity, such as high fat diet fed animals and determine the fate of the newly proliferated cells using dual immunofluorescence.
To assess metabolic and neuronal changes in high fat diet-fed animal, this study will apply a variety of techniques including, metabolic and behavioural testing, specific viral delivery of mutated molecules, and electrophysiology. The student will also learn stereotactic surgery to inject adenoviruses or lentiviruses to knockdown or overexpress insulin receptors or to restore insulin sensitivity through cannulae.
Students should be highly motivated and have a relevant degree in neuroscience or a related biomedical subject.