Lorise C. Gahring
Professor of Medicine and of Pathology
B.A. University of California, Irvine
Ph.D. University of Utah
Research
Whether considering Alzheimers, Parkinsons, Multiple Sclerosis, Epilepsy or just normal aging, inflammation is part of the disease pathogenesis. My lab studies several aspects of neuroinflammation that involve how inflammatory cytokines interact with neurotransmitter receptors. During the course of a peripheral inflammatory event, cytokines are produced locally and upon release into the blood stream stimulate cells within the central nervous system (CNS) to produce more cytokines. In most cases, inflammatory cytokines are produced transiently in the brain and have a positive effect on neuronal survival. Interleukin-1 ( a and b ), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF a ) can protect neurons against subsequent toxic challenges (including b -amyloid peptide, paraquat, and N-methyl-d-aspartic acid (NMDA)). Chronic stimulation of these inflammatory cytokines, however, can have deleterious effects on neuronal viability. Overexpression of inflammatory cytokines such as TNF a is detected in neurologic diseases. My laboratory investigates the effects of inflammatory cytokines on neurons through measuring intracellular events induced by these proteins.
A second emphasis of my laboratory is the study of neurotransmitter receptors that are expressed peripherally and how they impact upon inflammatory processes. While originally described as the receptor for acetycholine in the brain, neuronal nicotinic acetylcholine receptors (nAChR) are now known to be widely expressed peripherally in cells such as skin keratinocytes, lung epithelium and spleen lymphocytes. This non-neuronal expression of a neurotransmitter receptor in the periphery has been implicated in modulation of local inflammatory responses. We are investigating how nicotine (also an agonist of nAChR) affects peripheral (as well as central) inflammatory responses. Overall, our goal is to develop a mechanistic understanding of how inflammatory cytokines impact disease pathogenesis both centrally and peripherally and to determine how nicotine, or activation of nAChR, affects these processes.
References
1. Gahring LC, Persiyanov K, Rogers SW (2005) Mouse strain-specific changes in nicotinic expression with age. Neurobiology of Aging 26(6):973-80
2. Gahring LC, Persiyanov K, Days EL, Rogers SW (2005) Age-related loss of neuronal nicotinic receptor expression in the aging mouse hippocampus corresponds with cyclooxygenase 2 and PPAR g expression and is altered by long-term NS398 administration. J. Neurobiology 62:453-468
3. Gahring LC, Persiyanov K, Rogers SW (2004) Neuronal and Astrocyte Expression of Nicotinic Receptor Subunit Beta4 in the Adult Mouse Brain. J. Comparative Neurology 468:322-333
4. Gahring LC, Persiyanov K, Rogers SW (2004) Mouse Strain-Specific Nicotinic Acetylcholine Receptor Expression by Inhibitory Interneurons and Astrocytes in the Dorsal Hippocampus. J. Comparative Neurology 468:334-336
5. Gahring LC, Meyer EL, Rogers SW (2003) Nicotine-induced neuroprotection against NMDA or b-amyloid peptide occur through independent mechanisms distinguished by pro-inflammatory cytokines. J. Neurochemistry 87(5):1125-1136
6. Meyer EL, Strutz N, Gahring LC, Rogers SW (2003) Glutamate receptor subunit 3 is modified by site-specific limited proteolysis including cleavage by gamma-secretase. J. Biol. Chem. 278:23786-23796
7. Gahring LC, Rogers SW (2002) Autoimmunity to glutamate receptors in the central nervous system. Crit. Rev. Immunol. 22(4):295-316
8. Meyer EL, Gahring LC, Rogers SW ( 2002) Nicotine Preconditioning Antagonizes Activity-dependent Caspase Proteolysis of a Glutamate Receptor. J Biol. Chem. 277:10869-75
9. Gahring LC, Carlson NG, Meyer EL, Rogers SW (2001) Granzyme B Proteolysis of a Neuronal Glutamate Receptor Generates an Autoantigen is Modulated by Glycosylation. J. Immunol. 166:1452-1456
10. Carlson NG, Gahring LC, Rogers SW (2001) Identification of the Amino Acids on a Neuronal Glutamate Receptor Recognized by an Autoantibody from a Patient with Paraneoplastic Syndrome. J. Neurosci.Res. 63:480-485
11. Rogers SW, Gregori NZ, Carlson NG, Gahring LC, Noble M (2001) Neuronal Nicotinic Acetylcholine Receptor Expression by O-2A Glial Progenitor Cells. Glia 33:306-313
12. Carlson NC, Howard J, Gahring LC, Rogers SW (2000) RNA editing (Q/R site) and Flop/Flip splicing of AMPA receptor transcripts in young and old brains. Neurobiology of Aging 21(4):599-606
13. Gahring LC, Carlson NG, Wieggel WA, Howard J, Rogers SW (1999) Alcohol blocks TNFa but not other cytokine-mediated neuroprotection to NMDA. Alcoholism, Clin. and Exp. Res., 23:1571-1579
14. Carlson NG, Wieggel WA, Chen J, Bacchi A, Rogers SW, Gahring LC (1999) Inflammatory Cytokines IL-1a, IL-1ß, IL-6 and TNFa impart neuroprotection to an excitotoxin through distinct pathways. Journal of Immunology, 163:3963-3968
15. Gahring LC, Rogers SW (1998) Autoimmunity to glutamate receptors in Rasmussen's encephalitis: A rare finding or the tip of an iceberg? The Neuroscientist 4:373-379
16. Gahring LC, Carlson NC, Rogers SW (1998) Antibodies to neuronal glutamate receptor subunit 3 bind IFNa-receptors: Implications for an autoimmune process. Autoimmunity 28:243-248
17. Carlson NC, Bacchi A, Rogers SW, Gahring LC (1998) Nicotine blocks TNFa-mediated neuroprotection to NMDA by an a-bungarotoxin-sensitive pathway. J. Neurobiology 35:29-36
