Watt Lab

Overview or Research Interests

My overall research interest centers around the neuron/glial response(s) to brain injury particularly in regards to the mechanisms of cellular communication involved in regenerative events—both in terms of neuron to glial signals that induce activation of the appropriate glial response as well as the glia to neuron signals which may underlie or facilitate neural regeneration and repair. These signaling intermediates probably involve both cytokines and neurotrophins in complex communication loops. In order to facilitate our ability to define the communication loops activated during regenerative events, we have developed a model of compensatory sprouting by intact magnocellular neurosecretory axons following partial denervations of the posterior pituitary gland in the rat.

The response of the magnocellular neurosecretory system (MNS) to partial denervation is characterized by an initial period of axonal degeneration with concurrent alterations in perivascular microglial cell immunophenotypic characteristics and conversion to neuronophages. This event is followed by a much more prolonged period during which compensatory sprouting of uninjured axons occurs. This model of axonal plasticity avoids the extensive endocrine disruptions associated with stalk transaction and does not result in inflammation or invasion of the neurohypophysis by circulating macrophages. An additional advantage is that increased synthetic activity and secretory activity, with concomitant plastic responses within the terminal field, can be induced using non-invasive techniques such as oral salt-loading and chronic hyponatremia. Thus, it provides a useful model system with which to more thoroughly investigate the relationship between expression of cytokines, neurotrophins and their receptors by neurons and/or glial cells in response to injury and axonal sprouting.