Room 131, Sanders-Brown Center on Aging
800 South Limestone Street
Lexington, KY 40536-0230
Molecular and Biomedical Pharmacology
Calcium signaling pathways in brain aging and aging-related diseases
Irina Artiushin (Research Analyst)
Melanie Pleiss (Graduate Student)
Pradoldej Sompol (Postdoctoral Scholar)
Dr. Norris' work focuses on the role of Ca2+ signaling mechanisms in brain aging and neurodegenerative disease, with recent emphasis on the Ca2+/calmodulin dependent protein phosphatase, calcineurin, and its downstream targets. Most studies are conducted on the hippocampus, or hippocampal cultures using a variety of experimental approaches including: adenoviral-mediated gene delivery, electrophysiology (patch clamp and sharp electrode recordings), immunocytochemistry, and protein biochemistry. Behavioral assessment in rodents also is used to test brain-behavior relationships.
Alzheimer’s Research Forum: Chicago: NFATs, Calcineurin—Mediators of AD, PD Pathogenesis?
Alzheimer’s Research Forum: The Skinny on NFATs—Mediators of Aβ Toxicity?
Furman JL, Sama DM, Gant JC, Beckett TL, Murphy MP, Bachstetter AD, Van Eldik LJ, Norris CM (2012) Targeting astrocytes to ameliorates neurologic changes in a mouse model of Alzheimer’s disease. The Journal of Neuroscience, 32: 16129 –16140.
Bachstetter AD, Norris CM, Sompol P, Wilcock DM, Goulding D, Neltner JH, St Clair D, Watterson DM, Van Eldik LJ (2012) A small molecule suppressor of proinflammatory cytokine production attenuates glial activation and prevents synaptic dysfunction in an Alzheimer’s disease transgenic mouse model. The Journal of Neuroscience, 32:10201–10210.
Sama DM, Mohammad-Abdul, H, Furman JL, Szymkowski DE, Scheff SW, Norris CM (2012) Inhibition of soluble tumor necrosis factor ameliorates synaptic alterations and Ca2+ dysregulation in aged rats. PLoS ONE, 7(5):e38170.
Thibault O, Pancani T, Landfield PW, Norris CM (2012) Reduction in neuronal L-type Ca2+ channel current density in hippocampal “zipper” slices from mid-age memory-deficient APPxPS1 mice. Biochimica et Biophysica Acta, 1822:546-549.
Gant JC, Chen K-C, Norris CM, Thibault O, Blalock EM, Porter NM, Landfield PW (2011) Rapamycin or knockdown of FKBP12.6/1b recapitulates aging-like Ca2+ dysregulation in hippocampal neurons. The Journal of Neuroscience. 31:1593-1603
Mathis DM, Furman JL, Norris CM (2011) Preparation of acute hippocampal slices from rats and transgenic mice for the study of synaptic alterations during aging and amyloid pathology. Journal of Visualized Experiments, 49: http://www.jove.com/details.stp?id=2330
Mohmmad Abdul H, Baig I, Levine, H III, Guttmann RP, Norris CM (2011) Proteolysis of calcineurin is increased in human hippocampus during mild cognitive impairment and is stimulated in primary cultures by oligomeric Abeta. Aging Cell, 10: 103-113.
Abdul MH, Furman JL, Sama MA, Mathis DM, Norris CM (2010) NFATs and Alzheimer’s disease. Molecular and Cellular Pharmacology, 2:7-14.
Furman JL, Sama MA, Artiushin IA, Norris CM (2010) Disparate effects of serum on basal and evoked NFAT activity in primary astrocyte cultures. Neuroscience Letters 469:365–369.
Abdul MH, Sama MA, Furman JL, Mathis DM, Beckett TL, Weidner AM, Patel ES, Baig I, Levine, H III, Murphy MP, Kraner SD, Norris CM (2009) Cognitive decline in Alzheimer’s disease is associated with selective changes in calcineurin/NFAT signaling. The Journal of Neuroscience 29:12957–12969.
Norris CM, Scheff SW (2009) Recovery of afferent function and synaptic strength in hippocampal CA1 following traumatic brain injury. Journal of Neurotrauma 26:2269–2278.
Sama MA, Mathis DM, Furman JL, Artiushin IA, Mohmmad Abdul H, Kraner SD, Norris CM (2008) Interleukin-1b-dependent signaling between glia and neurons depends critically on astrocytic calcineurin/NFATactivity Journal of Biological Chemistry, 283:21953-21964.
Norris CM, Blalock EM, Chen K-C, Porter, NM, Thibault O, Kraner SD, Landfield PW (2010, online 2008) Hippocampal ‘zipper’ slice studies reveal a necessary role for calcineurin in the increased activity of L-type Ca2+ channels with aging. Neurobiology of Aging 31:328–338.
Jeftinija DM, Wang QB, Hebert SL, Norris CM,Yan Z, Rich MM, Kraner SD. The Ca(V) 1.2 Ca(2+) channel is expressed in sarcolemma of type I and IIa myofibers of adult skeletal muscle. Muscle Nerve 36: 482-490, 2007.
Norris CM, Blalock EM, Thibault O, Brewer LD, Clodfelter GV, Porter, NM, Landfield PW (2006) Electrophysiological Mechanisms of Delayed Excitotoxicity: Positive Feedback Loop Between NMDA Receptor Current and Depolarization-Mediated Glutamate Release. Journal of Neurophysiology 96:2488-2500.
Norris CM, Kadish I, Blalock EM, Chen KC, Thibault V, Porter NM, Landfield PW, and Kraner SD (2005). Calcineurin Triggers Reactive/Inflammatory Processes in Astrocytes and is Upregulated in Aging and Alzheimer’s Models. The Journal of Neuroscience 25:4649-4658.