Neurobiological basis of neurological and psychiatric diseases: Neurotrophic factors exert a powerful influence shaping the functional properties and biochemical make-up (i.e. the "neuronal phenotype") of neurons in specific brain regions. Long-term functional, and therefore behavioral, alterations in disease states or resulting from therapies could be achieved by regulating these factors or by modulating their signaling capacity. My laboratory focuses on the intracellular signaling mechanisms of these factors, how they are regulated, and how they relate to the biochemical and behavioral processes in disease states. The animal models include models of pathological states such as chronic stress and addiction, and also of therapeutic treatments, such as with antidepressant medications or dopamine agonists. In the adult, it appears that the role of the trophic factors themselves becomes relatively de-emphasized, and other intracellular molecules subsume these roles. We are dissecting the signaling mechanisms involved in these animal models, from the synapse to the level of transcription and chromatin reorganization, with the goals of achieving a better understanding of these basic processes and learning to modulate them for therapeutic benefit.

Russell, D.S. and Duman, R.S. “Neurotrophic factors and intracellular signal transduction pathways.” Neuropsychopharmacology: The Fifth Generation of Progress. David, K.L., Charney, D., Coyle, J.T. and Nemeroff, C. (eds.), Lippincott, Williams & Wilkins, New York (2002)

Sheehan, T.P., Neve, R.L., Duman, R.S., Russell, D.S. "Antidepressant effect of the calcium-activated tyrosine kinase Pyk2 in the lateral septum." Biol. Psychiatry 54:540-551 (2003)

Sheehan, T.P., Chambers, R.A., and Russell, D.S. "Regulation of affect by the lateral septum: Implications for neuropsychiatry." Brain Res. Rev. 46:71-117 (2004)

Shirayama, Y., Chen, A.C.-H., Nakagawa, S., Russell, D.S., and Duman, R.S. “Brain derived neurotrophic factor produces antidepreessant effects in behavioral models of depression.” J. Neurosci. 22:3251-3261 (2002)