Christopher M. Norris, PhD
Connect
Office (859) 218-2308cnorr2@email.uky.edu
Positions
- Professor, Department of Pharmacology & Nutritional Sciences
- Associate Director Sanders-Brown Center on Aging
- Co-Director Sanders-Brown Intravital Imaging Facility
College Unit(s)
Other Affiliation(s)
- Pharmacology and Nutritional Sciences Center Affiliated Faculty
- Neuroscience - Joint Faculty
Biography and Education
Biography
Research areas: Alzheimer's Disease and Related Dementias, Astrocyte Physiology, Ca2+ signaling, Calcineurin/NFAT Signaling, Glutamate Regulation, Synaptic Function, Cerebrovascular Function
Personal Skillsets: Electrophysiology
Lab Skillsets: Intravital Two Photon Imaging, Virus-mediated Gene Delivery, Brain Slice Electrophysiology, Microelectrode Array-Based In Vivo Neurochemistry, Protein Biochemistry, Confocal Microscopy, Small Rodent Behavioral Assessment, Canine Behavioral Assessment
Education
BA Psychology, Washington & Jefferson College, Washington, PA, 1992
MA Experimental Psychology, Wake Forest University, Winston-Salem, NC 1994
PhD Neuroscience, University of Virginia, Charlottesville, VA, 1998
Research
Our lab uses postmortem human tissue samples, transgenic rodents, and primary neural cultures to investigate the role of reactive astrocytes in neurologic dysfunction and to develop novel strategies for treating neurodegenerative conditions like Alzheimer’s disease and vascular contributions to cognitive impairment and dementia. Astrocyte signaling pathways are selectively targeted in model systems using adeno-associated virus vectors equipped with cell-type specific promoters. Markers of aging, vascular injury, and/or Alzheimer’s disease are assessed using a comprehensive set of approaches including multiphoton microscopy, brain slice and patch clamp electrophysiology, immunohistochemistry, behavioral characterization, and a variety of molecular and biochemical techniques.
An additional project in the lab (conducted at Spindle Top Kennels, and in collaboration with Dr. Elizabeth Head at the University of California, Irvine) longitudinally investigates the effects of FDA approved and experimental pharmacologic compounds on cognition, brain microstructure, cerebral blood flow, and metabolism (using MRI/MRS), and blood and CSF biomarkers in an aging canine model of Alzhiemer's disease.
We are a highly collaborative group with shared grants and manuscripts with colleagues across the Center on Aging, Department of Pharmacology, and College of Medicine.
SBCOA Lab Personnel and Colleagues:
Bob Sompol, PhD, Assistant Professor
Susan Kraner, PhD, Scientist III
Chris Gant, PhD, Scientist III
Jenna Gollihue, PhD, Postdoc
Ed Rucker, PhD, Scientist IV
Irina Artiushin, MS, Research Analyst
Blaine Weiss, BS, Graduate Student
Susan Craddock, STEPS
Margo Ubele, MS, Project Manager
Spindle Top Kennels:
Margo Ubele, MS, Project Manager
Kathy Boaz, Research Associate
Erin Jones, Animal Care Supervisor I
Jennifer Mefford, Animal Care Technician III
Selected Publications
Sordo L, Ubele MF, Boaz KA, Mefford JL, Denhart Jones E, McCarty KL, van Rooyen HY, Smiley JR, Bembenek Bailey SA, Perpich JA, Meacham B, Powell DK, Bresch FE, Crump JW, Phelan MJ, Noche JA, Stark CE, Puskás LG, Norris CM, Head E (2024) Calcineurin/NFAT Inhibitors maintain cognition in a preclinical prevention study in an aging canine model of Alzheimer's disease. Neurobiology of Aging, 146:1-14. doi: 10.1016/j.neurobiolaging.2024.11.003.
Niedowicz DM, Wang W-X, Prajapati P, Zhong Y, Fister S, Rogers CB, Sompol P, Powell DK, Patel I, Norris CM, Saatman KE, Nelson PT (2024) Nicorandil treatment improves survival and spatial learning in aged granulin knockout mice. Brain Pathology, doi: 10.1111/bpa.13312.
Jiang Y, Neal J, Sompol P, Yener G, Arakaki X, Norris CM, Farina FR, Ibanez A, Lopez S, Al-Ezzi A, Kavcic V, Guntekin B, Babiloni C, Hajos M (2024) Parallel Electrophysiological Abnormalities due to COVID-19 Infection and to Alzheimer’s Disease and Related Dementia. Alzheimer’s & Dementia, 20:7296–7319.
Weiss BE, Kraner SD, Artiushin IA, Norris CM (2024). Elevated calcineurin activity in primary astrocytes leads to the dephosphorylation of connexin 43 in conjunction with increased membrane permeability. NeuroReport, 35:673-678.
Noche JA, Radhakrishnan H, Ubele MF, Boaz K, Mefford JL, Jones ED, Perpich JA, McCarty K, Meacham B, Smiley J, Bembenek Bailey SA, Puskas LG, Powell DK, Sordo L, Phelan MJ, Norris CM, Head E, Stark CEL (2024) Age-related atrophy and the positive effects of behavioral enrichment in middle-aged beagles. The Journal of Neuroscience, 44 (20) e2366232024; DOI: https://doi.org/10.1523/JNEUROSCI.2366-23.2024.
Hossain R, Noonong K, Nuinoon M, Lao-On U, Norris CM, Sompol P, Rahman MA, Majima HJ, Tangpong J. (2024) Alzheimer’s diseases in America, Europe, and Asian regions: A scoping review of global genetic variation. PeerJ, 12:e17339, doi: 10.7717/peerj.17339.
Niedowicz DM, Gollihue JL, Weekman EM, Phe P, Wilcock DM, Norris CM, Nelson PT (2024) Using digital pathology to analyze the murine cerebrovasculature. Journal of Cerebral Blood Flow and Metabolism, 21: 44:595-610
Kraner SD, Sompol P, Prateeptrang S, Promkan M, Hongthong S, Thongsopha N, Kongpol K, Nelson PT, Norris CM (2024) Development of a monoclonal antibody specific for a calpain-generated ∆48 kDa calcineurin fragment, a marker of distressed astrocytes. Journal of Neuroscience Methods, 402:110012. doi: 10.1016/j.jneumeth.2023.110012
Norris CM (2023) Is it time to repurpose calcineurin inhibitors for the treatment of cognitive impairment and dementia? Journal of Alzheimer’s Disease, 95:599-602.
Sompol P, Gollihue JL, Weiss BE, Lin RL, Case SL, Kraner SD, Weekman EM, Gant JC, Rogers CB, Niedowicz DM, Sudduth TL, Powell DK, Lin AL, Nelson PT, Thibault O, Wilcock DM, Norris CM (2023) Targeting astrocyte signaling alleviates cerebrovascular and synaptic function deficits in a diet-based mouse model of small cerebrovessel disease. The Journal of Neuroscience 43:1797-1813.
MacPherson KP, Eidson LN, Weiss BE, Gollihue JL, Herrick MK, Houser MC, De Sousa Rodrigues ME, Sniffen L, Weekman EM, Hamilton AM, Kelly SD, Oliver D, Yang Y, Chang J, Sampson T, Norris CM, Tansey MG (2023) Soluble TNF mediates amyloid independent, diet-induced alterations to immune and neuronal functions in an Alzheimer's disease mouse model. Frontiers in Cellular Neuroscience, 17: DOI=10.3389/fncel.2023.895017.
Sompol P, Gollihue JL, Kraner SD, Artiushin IA, Cloyd RA, Chishti EA, Koren SA, Nation GK, Abisambra JF, Huzian O, Nagy LI, Santha M, Hackler L Jr, Puskas LG, Norris CM (2021) Q134R: Small chemical compound with NFAT inhibitory properties improves behavioral performance and synapse function in mouse models of amyloid pathology. Aging Cell 20(7):e13416.doi: 10.1111/acel.13416.
Radhakrishnan H, Ubele MF, Krumholz SM, Boaz K, Mefford JL, Jones ED, Meacham B, Smiley J, Puskás LG, Powell DK, Norris CM, Stark CEL, Head E.(2021) Tacrolimus protects against age-associated microstructural changes in the beagle brain. The Journal of Neuroscience 41:5124-5133.
Price BR, Johnson LA, Norris CM (2021) Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer's disease. Ageing Research Reviews. 68:101335.doi: 10.1016/j.arr.2021.101335.
Escartin C, Galea E, Lakatos A, O'Callaghan JP, Petzold GC, Serrano-Pozo A, Steinhäuser C, Volterra A, Carmignoto G, Agarwal A, Allen NJ, Araque A, Barbeito L, Barzilai A, Bergles DE, Bonvento G, Butt AM, Chen WT, Cohen-Salmon M, Cunningham C, Deneen B, De Strooper B, Díaz-Castro B, Farina C, Freeman M, Gallo V, Goldman JE, Goldman SA, Götz M, Gutiérrez A, Haydon PG, Heiland DH, Hol EM, Holt MG, Iino M, Kastanenka KV, Kettenmann H, Khakh BS, Koizumi S, Lee CJ, Liddelow SA, MacVicar BA, Magistretti P, Messing A, Mishra A, Molofsky AV, Murai KK, Norris CM, Okada S, Oliet SHR, Oliveira JF, Panatier A, Parpura V, Pekna M, Pekny M, Pellerin L, Perea G, Pérez-Nievas BG, Pfrieger FW, Poskanzer KE, Quintana FJ, Ransohoff RM, Riquelme-Perez M, Robel S, Rose CR, Rothstein JD, Rouach N, Rowitch DH, Semyanov A, Sirko S, Sontheimer H, Swanson RA, Vitorica J, Wanner IB, Wood LB, Wu J, Zheng B, Zimmer ER, Zorec R, Sofroniew MV, Verkhratsky A (2021) Reactive astrocyte nomenclature, definitions, and future directions. Nature Neuroscience. 24:312-325.
Frazier HL, Anderson KL, Ghoweri AO, Lin RL, Hawkinson TR, Popa GJ, Sompol P, Mendenhall MD, Norris CM, Thibault O (2020) Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats. Aging Cell, 19(10):e13220. doi: 10.1111/acel.13220. Epub 2020 Aug 27
Fu X, Sompol P, Brandon JA, Norris CM, Wilkop T, Johnson LA, Richards CI (2020) In vivo single-molecule detection of nanoparticles for multiphoton fluorescence correlation spectroscopy to quantify cerebral blood flow. Nano Letters, 20:6135-6141.
Dufort-Gervais J, Provost C, Charbonneau L, Norris CM, Calon F, Mongrain V, Brouillette J (2020) Neuroligin-1 is altered by amyloid-beta oligomers and modulates their toxicity. Scientific Reports, 10:6956. doi: 10.1038/s41598-020-63255-6.
Gollihue JL, Norris CM (2020) Astrocyte mitochondria: Central players and potential therapeutic targets for neurodegenerative diseases and injury. Ageing Research Reviews, 59:101039. doi: 10.1016/j.arr.2020.101039.
Quadri Z, Johnson N, Zamudioa F, Miller A, Peters M, Smeltzer S, Hunt JB, Housley SB, Brown B, Kraner SD, Norris CM, Nash K, Weeber E, Lee DC, Selenica M-L (2020) Overexpression of human wtTDP-43 causes impairment in hippocampal plasticity and behavioral deficits in CAMKII-tTa transgenic mouse model. Molecular and Cellular Neuroscience, 102:103418. doi: 10.1016/j.mcn.2019.103418.
Thalman SW, Powell DK, Ubele M, Norris CM, Head E, Lin AL (2019) Brain-blood partition coefficient and cerebral blood flow in canines using Calibrated Short TR Recovery (CaSTRR) correction method. Frontiers in Neuroscience, 13:1189. doi: 10.3389/fnins.2019.01189.
Braun D, Abner EL, Bakshi V, Goulding D, Grau EM, Lin AL, Norris CM, Sudduth TL, Webster SJ, Wilcock DM, Van Eldik LJ (2019) Blood flow deficits and cerebrovascular changes in a hyperhomocysteinemia model of vascular cognitive impairment and dementia. ASN Neuro, 11:1759091419865788 doi: 10.1177/1759091419865788.
Frazier HN, Anderson KL, Maimaiti S, Ghoweri AO, Kraner SD, Popa GJ, Hampton KK, Mendenhall MD, Norris CM, Craven RJ, Thibault O (2019) Expression of a constitutively active human insulin receptor in hippocampal neurons elevates signaling but does not alter VGCC currents. Neurochemical Research, 44:269-280.
Norris CM (2018) Calcineurin: Directing the damage in Alzheimer’s disease? Journal of Neurochemistry 147:8-11.
Kraner SD, Norris CM (2018) Astrocyte activation and the calcineurin/NFAT pathway in cerebrovascular disease. Frontiers in Aging Neuroscience, 10:287. doi: 10.3389/fnagi.2018.00287
Sompol P, Norris CM (2018). Ca2+, astrocyte activation, and calcineurin/NFAT signaling in age-related neurodegenerative diseases. Frontiers in Aging Neuroscience, 10:199. doi: 10.3389/fnagi.2018.00199.
Castonguay D, Dufort-Gervais J, Ménard C, Chatterjee M, Quirion R, Bontempi B, Schneider JS, Arnsten AFT, Nairn AC, Norris CM, Ferland G, Bézard E, Gaudreau P, Lombroso PL, Brouillette J (2018) The tyrosine phosphatase STEP is involved in age-related memory decline. Current Biology, 28:1079-1089.
Price PR, Sompol P, Norris CM, Wilcock DM (2018) An emerging role of astrocytes in vascular contributions to cognitive impairment and dementia (VCID). Journal of Neurochemistry, 144:644-650.
Sompol P, Furman JL, Pleiss MM, Kraner SD, Artiushin IA, Batten SR, Quintero JE, Simmerman LA, Beckett TL, Lovell MA, Murphy MP, Gerhardt GA Norris CM (2017) Calcineurin/NFAT signaling in activated astrocytes drives network hyperexcitability in Aβ-bearing mice. The Journal of Neuroscience, 37:6132-6148.
Manocha GD, Ghatak A, Puig KL, Kraner SD, Norris CM, Combs KL (2017) NFATc2 Modulates Microglial Activation in the AβPP/PS1 Mouse Model of Alzheimer’s Disease. Journal of Alzheimer’s Disease, 58:775-787.
MacPherson KP, Sompol P, Kannarkat G, Chang J, Sniffen L, Wildner ME, Norris CM, Tansey MG (2017) Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice. Neurobiology of Disease, 102:81-95.
Sudduth TL, Weekman EM, Price BR, Gooch JL, Woolums A, Norris CM, Wilcock DM (2017) Time-course of glial changes in the hyperhomocysteinemia model of vascular cognitive impairment and dementia (VCID). Neuroscience 341:42-51.
Pleiss MM, Sompol P, Kraner SD, Mohmmad Abdul H, Furman JL, Guttmann RP, Wilcock DM, Nelson PT, Norris CM (2016) Calcineurin proteolysis in astrocytes: Implications for impaired synaptic function. Biochimica et Biophysica Acta 1862:1521-1532.
Lovell MA, Lynn BC, Fister S, Bradley-Whitman M, Murphy MP, Beckett TL, Norris CM, (2016) A novel small molecule modulator of amyloid pathology. Journal of Alzheimer’s Disease 53:273-287.
Pettigrew LC, Kryscio RJ, Norris CM (2016) The TNFα-Transgenic Rat: Hippocampal synaptic integrity, cognition, function, and post- ischemic cell loss. PLOS ONE, 11(5): e0154721. doi:10.1371/journal.pone.0154721 -- 20 page article
Furman JL, Sompol P, Kraner SD, Pleiss MM, Putman EJ, Dunkerson J, Mohmmad Abdul H, Scheff SW, Norris CM (2016) Blockade of astrocytic calcineurin/NFAT signaling helps to normalize hippocampal synaptic function and plasticity in a rat model of traumatic brain injury. The Journal of Neuroscience 36:1502-1515.
Norris CM, Sompol P, Roberts KN, Ansari M, Scheff SW (2016) Pycnogenol protects CA3-CA1 synaptic function in a rat model of traumatic brain injury. Experimental Neurology 276:5-12.
Furman JL Norris CM (2014) Calcineurin and glial signaling: Neuroinflammation and beyond. Journal of Neuroinflammation 11:158.
Gant JC, Blalock EM, Chen KC, Kadish I, Porter NM, Norris CM, Thibault O, Landfield PW (2014) FK506-binding protein 1b/12.6: A key to aging-related hippocampal Ca2+ dysregulation? European Journal of Pharmacology 739:74-82.
Niedowicz DM, Reeves VL, Platt TL, Kohler K, Beckett TL, Powell DK, Lee TL, Sexton TR, Song ES, Brewer LD, Latimer CS, Kraner SD, Larson KL, Ozcan S, Norris CM, Hersh LB, Porter NM, Wilcock DM, Murphy MP (2014) Obesity and diabetes cause cognitive dysfunction in the absence of accelerated β-amyloid deposition in a novel murine model of mixed or vascular dementia. Acta Neuropathologica Communications 2:64.
Wang W-X, Danaher J, Miller CS, Berger JR, Vega NG, Wilfred BS, Neltner JH, Norris CM, Nelson PT (2014) Expression of MiR-15/107 family microRNAs in human tissues and rat brain cells. Genomics, Proteomics & Bioinformatics 12:19-30.
Norris CM (2014) Calpain interactions with the protein phosphatase calcineurin in neurodegeneration. Advances in Biochemistry in Health and Disease. 8:17-45.
Sama DM, Norris CM (2013) Calcium dysregulation and neuroinflammation: Discrete and integrated mechanisms for age-related synaptic dysfunction. Ageing Research Reviews, 12:982-95.
Furman JL, Sama DM, Gant JC, Beckett TL, Murphy MP, Bachstetter AD, Van Eldik LJ, Norris CM (2012) Targeting astrocytes 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.
Norris CM, Blalock EM, Chen K-C, Porter, NM, Thibault O, Kraner SD, Landfield PW (2010) 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.
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-1-dependent signaling between glia and neurons depends critically on astrocytic calcineurin/NFATactivity. Journal of Biological Chemistry 283:21953-21964
Jeftinija DM, Hebert SL, Norris CM, Wang QB, Rich MM, Kraner SD (2007) The CaV 1.2 Ca2+ channel is expressed in the sarcolemma of type I and IIa skeletal muscle fibers. Muscle & Nerve 36: 482–490.
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.
Blalock EM, Chen K-C, Stromberg AJ, Norris CM, Kadish I, Kraner SD, Porter NM, Landfield PW (2005) Harnessing the power of gene microarrays for the study of brain aging and Alzheimer’s disease: Statistical reliability and functional correlation. Ageing Research Reviews 4:481-512.
Norris CM, Kadish I, Blalock EM, Chen KC, Thibault V, Porter NM, Landfield PW, 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.