Jyoti J. Watters

 

 

Signal Transduction and Gene Expression in Microglia

E-mail: jjwatters@wisc.edu

Research Strengths: Molecular Neuroscience, Neurobiology of Disease

Hyperactivation of microglial cells has been implicated in the progression and neuronal injury sustained as a result of several neurodegenerative and inflammatory diseases. Microglia, mononuclear phagocytic immune cells residing in the CNS, are among the first cell types to respond to neuronal injury. Upon their activation, they synthesize and secrete inflammatory mediators that can be neurotoxic when produced in excess. Therefore, identification of agents that can reduce or prevent their activation is of great clinical importance. In my lab, we study two such substances: 1) extracellular adenine nucleotides such as ATP, which are important components of the inflammatory microenvironment, and 2) estrogens, which are thought to play a role in the gender prevalence of many neurodegenerative diseases. Our research interests are centered on understanding the signal transduction mechanisms in microglia that result in their production of pro- and anti-inflammatory agents in response to activating stimuli such as bacterial cell wall components, hypoxia and brain tumor growth. In addition, we are studying how ATP and estrogens alter these pathways in order to reduce microglial activation and their production of neurotoxic substances. Delineating the molecular mechanisms involved in microglial cell production of inflammatory mediators will lead to the identification of novel therapeutic targets, either receptors or signaling molecules/pathways, which can be exploited to minimize brain damage ensuing from neurodegenerative and inflammatory processes.

Lab Website:

http://www.vetmed.wisc.edu/cbs/watters2/

Selected Publications:

• Brautigam, V.M., G.R. Dubyak, J.M. Crain, and J.J. Watters. 2008 The inflammatory effects of UDP-Glucose in N9 microglia are not mediated by P2Y14 receptor activation. Purinergic Signaling. 4:73-78. [PDF]
• Potucek, Y.D., J.M. Crain, and J.J. Watters. 2006. Purinergic receptors modulate MAP kinases and transcription factors that control microglial inflammatory gene expression. Neurochem. Int'l. 49:204-214. [PDF]
• Nikodemova, M., I.D. Duncan, and J.J. Watters. 2006. Minocycline exerts inhibitory effects on multiple members of the mitogen-activated protein kinases in a stimulus specific manner in microglia in vitro. J. Neurochemistry 96: 314-323.
• Brautigam, V.M., C. Frasier, M. Nikodemova, and J.J. Watters. 2005. Purinergic receptor modulation of BV-2 microglial cell activity: Potential involvement of p38 MAP kinase and CREB. J. Neuroimmunol. 166:113-125.
• Watters, J.J., J.M. Schartner, B. Badie. 2005. Microglia function in brain tumors. J. Neurosci. Res. 81: 447-455.
• Baker, A.E., V. Brautigam, and J.J. Watters. 2004 The anti-inflammatory of effects of estrogen in murine BV-2 microglia are mediated by estrogen receptor b. Endocrinology. 145: 5021-5032. [PDF]