Titles and Education
- 1997 Ph.D.- Pharmacology, University of Washington, Seattle
- 1990 B.S. - Microbiology and Immunology, University of Arizona, Tucson
Microglia (CNS resident immune cells) display extraordinary cellular plasticity to support their role in every aspect of brain health and disease. With activities ranging from resting surveillance, to inflammatory activation, to neurotrophic/reparative activities, microglia participate in protecting and repairing the CNS during injury or disease. However, when their activities become dysregulated, they can contribute to neurodevelopmental disorders, and exacerbate ongoing neurodegenerative pathology. Hypoxia is a common co-occurrence in many CNS diseases, yet we understand very little about how hypoxia modifies microglial responses to neural insults or disease processes. We use a rodent model of chronic neuroinflammation that is induced by intermittent hypoxia, an aspect of sleep disordered breathing. Most recently, we have become interested in how fetal exposure to intermittent hypoxia during pregnancy impacts offspring brain development and function. We study the role of epigenetic modifications to DNA and histones, and the function of microRNAs in offspring microglia, and focus on how resulting alterations in microglial activities impact neuroplasticity and neural function, including breathing disruption and cognitive behaviors. A key aspect of our research centers on understanding differences between male and female microglial responses, and how these sexual dimorphisms influence CNS function and neuroplasticity. We suggest that early life exposure to intermittent hypoxia may reprogram microglia in the developing central nervous system, predisposing to aberrant immune responses and neural disease later in life, many of which are sexually dimorphic. Our research goal is to better understand the aspects below in order to identify novel therapeutic targets to treat neural disorders.
- Impact of early life sleep disordered breathing on offspring microglia
- Role of microglia in neuroplasticity and cognitive function
- Epigenetic regulation of microglial gene transcription
- Microglial signal transduction mechanisms in paradigms of hypoxia
- Sex differences in microglial responses and their contributions to neural disorders
- Veterinary Pharmacology 934:552 - topics: receptor signal transduction mechanisms; autonomic nervous system drugs; cardiorespiratory pharmacology; endocrine/steroid receptor signaling; anti-inflammatories and cancer drugs.
- Comparative Biomedical Sciences Graduate Program
- Neuroscience Training Program
- Cell and Molecular Biology Training Program
- Molecular and Environmental Toxicology
- Cellular and Molecular Pathology
- Molecular and Cellular Pharmacology
Kiernan, E.A., Wang, T., Vanderplow, A.M., Cherukuri, S., Cahill, M.E., Watters, J.J. 2019 Neonatal Intermittent Hypoxia Induces Lasting Sex-Specific Augmentation of Rat Microglial Cytokine Expression. Front. Immunol. 10:1479.
- Johnson, S.M., Randhawa, K.S., Epstein, J.J., Gustafson, E., Hocker, A.D., Huxtable, A.G., Baker, T.L. and Watters, J.J. 2018 Gestational intermittent hypoxia increases susceptibility to neuroinflammation and alters respiratory motor control in neonatl rats. Respiratory Physiology and Neurobiology, 256: 128-142.
- Dougherty, B.J., Kopp, E.S. and Watters, J.J. 2017 Non-genomic actions of 17-β estradiol restore respiratory neuroplasticity in young ovariectomized female rats. J. Neuroscience, 37(28):6648-6660.
- Cheng, K.P., Elicieri, K.W., Williams, J.C. and Watters, J.J. 2016 Blue light modulates murine microglial gene expression in the absence of optogenetic protein expression. Nature Scientific Reports, 6:21172
Nikodemova, M., Kimyon, R.S., De, I., Small, A.L., Collier, L.S. and Watters, J.J. 2015 Microglial numbers attain adult levels after undergoing a rapid decrease in cell number in the third postnatal week. Journal of Neuroimmunology, 278:280-288
Smith, S.M.C., Kimyon, R.S. and Watters, J.J. 2014 Cell-Type Specific Expression of Jumonji Histone Demethylases in the Healthy Rat CNS: Detection By A Novel Flow Cytometry Method. ASN Neuro, 6(3) pii: e00146.
Nikodemova, M., Small, A.L., Smith, S.M., Mitchell, G.S. and Watters. J.J. 2014 Spinal but not cortical microglia acquire an atypical phenotype with high VEGF, galectin-3 and osteopontin, and blunted inflammatory responses in ALS rats. Neurobiology of Disease, 69C:43-53.
Smith, S.M.C., Mitchell, G.S., Friedle, S.A. and Watters, J.J. 2013 Chronic intermittent hypoxia exerts CNS region-specific effects on rat microglial inflammatory and TLR4 gene expression. PLoS One, 8(12):e81584.
- Nikodemova, M. and Watters, J.J. 2012 Efficient Isolation of Live Microglia with Preserved Phenotypes from Adult Mouse Brain. J. Neuroinflammation. 9:147.
- Friedle, S.A., Nikodemova, M., Wright, M.L. and Watters, J.J. 2011 The P2X7-Egr Pathway Regulates Nucleotide-Dependent Inflammatory Gene Expression in Microglia. Glia. 59(1):1-13.
- Crain, J.M., Nikodemova, M. and Watters, J.J. 2009 Purinergic receptor expression varies with age and sex in freshly isolated brain microglia. J. Neuroinflammation, 6(1):24.