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Robert A. Nichols, Ph.D.

TitleDirector, Neuroscience Specialization
Faculty RankProfessor
InstitutionUniversity of Hawaii
DepartmentCell and Molecular Biology
AddressJohn A. Burns School of Medicine
University of Hawaii at Manoa
651 Ilalo Street
Honolulu HI 96813
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    Collapse Overview 
    Collapse overview
    Our laboratory is investigating the impact of beta amyloid, one of the major pathogenic elements in Alzheimer's disease, on synaptic function and toxicity. At 'physiological' levels of beta amyloid (pM), it appears to act as a positive neuromodulator. As beta amyloid accumulates in Alzheimer's disease, its action turns to toxicity. Recently, we have found that the presence of nicotinic receptors, putative targets for beta amyloid, sensitizes neurons to toxic action of beta amyloid.
    Approaches in use:
    Transfected neuronal cell lines
    Primary neuronal cultures; Primary slice cultures
    Calcium Imaging
    Neurotransmitter release assays
    Mitochondrial function
    Oxidative stress
    Immunoblot analysis
    Extracellular recording in hippocampal slices (LTP; PPF)
    Contextual fear conditioning

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Lantz MJ, Roberts AM, Delgado DD, Nichols RA. The neuroprotective N-terminal amyloid-? core hexapeptide reverses reactive gliosis and gliotoxicity in Alzheimer's disease pathology models. J Neuroinflammation. 2023 May 27; 20(1):129. PMID: 37245024.
      Citations:    Fields:    Translation:HumansAnimalsCells
    2. Nichols RA, Gulisano W, Puzzo D. Editorial: Beta Amyloid: From Physiology to Pathogenesis. Front Mol Neurosci. 2022; 15:876224. PMID: 35359578.
    3. Xu M, Lantz MJ, Nichols RA, Li QX. Anti-Neuroinflammatory Effects of a Semi-Synthetic Isoorientin-Based Glycogen Synthase Kinase-3? Inhibitor in Lipopolysaccharide-Activated Microglial Cells. ACS Chem Neurosci. 2022 01 05; 13(1):43-52. PMID: 34913695.
      Citations:    Fields:    Translation:AnimalsCells
    4. Liu Q, Zhang L, Allman EL, Hubbard TD, Murray IA, Hao F, Tian Y, Gui W, Nichols RG, Smith PB, Anitha M, Perdew GH, Patterson AD. The aryl hydrocarbon receptor activates ceramide biosynthesis in mice contributing to hepatic lipogenesis. Toxicology. 2021 06 30; 458:152831. PMID: 34097992.
      Citations: 5     Fields:    Translation:HumansAnimalsCells
    5. Forest KH, Taketa R, Arora K, Todorovic C, Nichols RA. The Neuroprotective Beta Amyloid Hexapeptide Core Reverses Deficits in Synaptic Plasticity in the 5xFAD APP/PS1 Mouse Model. Front Mol Neurosci. 2021; 14:576038. PMID: 33912008.
    6. Cai C, Li C, Sun R, Zhang B, Nichols RL, Hake KD, Pan X. Small RNA and degradome deep sequencing reveals important roles of microRNAs in cotton (Gossypium hirsutum L.) response to root-knot nematode Meloidogyne incognita infection. Genomics. 2021 05; 113(3):1146-1156. PMID: 33667647.
      Citations: 6     Fields:    Translation:Animals
    7. Roberts JP, Stokoe SA, Sathler MF, Nichols RA, Kim S. Selective coactivation of a7- and a4?2-nicotinic acetylcholine receptors reverses beta-amyloid-induced synaptic dysfunction. J Biol Chem. 2021 Jan-Jun; 296:100402. PMID: 33571523.
      Citations: 16     Fields:    Translation:HumansAnimalsCells
    8. Tan X, Liang Z, Li Y, Zhi Y, Yi L, Bai S, Forest KH, Nichols RA, Dong Y, Li QX. Isoorientin, a GSK-3? inhibitor, rescues synaptic dysfunction, spatial memory deficits and attenuates pathological progression in APP/PS1 model mice. Behav Brain Res. 2021 02 01; 398:112968. PMID: 33069740.
      Citations: 8     Fields:    Translation:AnimalsCells
    9. Arora K, Belcaid M, Lantz MJ, Taketa R, Nichols RA. Transcriptome Profile of Nicotinic Receptor-Linked Sensitization of Beta Amyloid Neurotoxicity. Sci Rep. 2020 03 30; 10(1):5696. PMID: 32231242.
      Citations: 4     Fields:    Translation:HumansAnimalsCells
    10. Zhang L, Rimal B, Nichols RG, Tian Y, Smith PB, Hatzakis E, Chang SC, Butenhoff JL, Peters JM, Patterson AD. Perfluorooctane sulfonate alters gut microbiota-host metabolic homeostasis in mice. Toxicology. 2020 02 15; 431:152365. PMID: 31926186.
      Citations: 15     Fields:    Translation:Animals
    11. Forest KH, Nichols RA. Assessing Neuroprotective Agents for A?-Induced Neurotoxicity. Trends Mol Med. 2019 08; 25(8):685-695. PMID: 31248781.
      Citations: 8     Fields:    Translation:HumansAnimalsCells
    12. Wang XQ, Allen TW, Wang H, Peterson DG, Nichols RL, Liu A, Li XD, Deng P, Jia D, Lu SE. Development of a qPCR Protocol to Detect the Cotton Bacterial Blight Pathogen, Xanthomonas citri pv. malvacearum, from Cotton Leaves and Seeds. Plant Dis. 2019 Mar; 103(3):422-429. PMID: 30632895.
      Citations: 2     Fields:    Translation:AnimalsCells
    13. Puckhaber LS, Zheng X, Bell AA, Stipanovic RD, Nichols RL, Liu J, Duke SE. Differences in Active Defense Responses of Two Gossypium barbadense L. Cultivars Resistant to Fusarium oxysporum f. sp. vasinfectum Race 4. J Agric Food Chem. 2018 Dec 12; 66(49):12961-12966. PMID: 30380850.
      Citations:    Fields:    Translation:Animals
    14. Tian Y, Cai J, Gui W, Nichols RG, Koo I, Zhang J, Anitha M, Patterson AD. Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation. Drug Metab Dispos. 2019 02; 47(2):86-93. PMID: 30409838.
      Citations: 36     Fields:    Translation:AnimalsCells
    15. Pathak P, Xie C, Nichols RG, Ferrell JM, Boehme S, Krausz KW, Patterson AD, Gonzalez FJ, Chiang JYL. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism. Hepatology. 2018 10; 68(4):1574-1588. PMID: 29486523.
      Citations: 167     Fields:    Translation:AnimalsCells
    16. Morel C, Sherrin T, Kennedy NJ, Forest KH, Avcioglu Barutcu S, Robles M, Carpenter-Hyland E, Alfulaij N, Standen CL, Nichols RA, Benveniste M, Davis RJ, Todorovic C. JIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory. J Neurosci. 2018 04 11; 38(15):3708-3728. PMID: 29540552.
      Citations: 14     Fields:    Translation:AnimalsCells
    17. Kabbani N, Nichols RA. Beyond the Channel: Metabotropic Signaling by Nicotinic Receptors. Trends Pharmacol Sci. 2018 04; 39(4):354-366. PMID: 29428175.
      Citations: 56     Fields:    Translation:HumansAnimalsCells
    18. Berry M, Chen J, Hixon A, Gerschenson M, James N, Jameson D, Lew HL, Lozanoff S, Nichols R, Seifried S, Teshima D, Masaki K, Tam E, Ward B, Ward S. Medical School Hotline: School of Medicine Departments - Year in Review 2017, Part 1. Hawaii J Med Public Health. 2018 01; 77(1):14-16. PMID: 29333336.
      Citations:    Fields:    Translation:Humans
    19. Forest KH, Alfulaij N, Arora K, Taketa R, Sherrin T, Todorovic C, Lawrence JLM, Yoshikawa GT, Ng HL, Hruby VJ, Nichols RA. Protection against ?-amyloid neurotoxicity by a non-toxic endogenous N-terminal ?-amyloid fragment and its active hexapeptide core sequence. J Neurochem. 2018 01; 144(2):201-217. PMID: 29164616.
      Citations: 15     Fields:    Translation:AnimalsCells
    20. Tian Y, Nichols RG, Cai J, Patterson AD, Cantorna MT. Vitamin A deficiency in mice alters host and gut microbial metabolism leading to altered energy homeostasis. J Nutr Biochem. 2018 04; 54:28-34. PMID: 29227833.
      Citations: 32     Fields:    Translation:Animals
    21. Hubbard TD, Murray IA, Nichols RG, Cassel K, Podolsky M, Kuzu G, Tian Y, Smith P, Kennett MJ, Patterson AD, Perdew GH. Dietary Broccoli Impacts Microbial Community Structure and Attenuates Chemically Induced Colitis in Mice in an Ah receptor dependent manner. J Funct Foods. 2017 Oct; 37:685-698. PMID: 29242716.
    22. Crutcher FK, Puckhaber LS, Bell AA, Liu J, Duke SE, Stipanovic RD, Nichols RL. Detoxification of Fusaric Acid by the Soil Microbe Mucor rouxii. J Agric Food Chem. 2017 Jun 21; 65(24):4989-4992. PMID: 28538103.
      Citations: 4     Fields:    Translation:AnimalsCellsPHPublic Health
    23. Nichols RG, Hume NE, Smith PB, Peters JM, Patterson AD. Omics Approaches To Probe Microbiota and Drug Metabolism Interactions. Chem Res Toxicol. 2016 12 19; 29(12):1987-1997. PMID: 27782392.
      Citations: 3     Fields:    Translation:HumansAnimals
    24. Zhang L, Xie C, Nichols RG, Chan SH, Jiang C, Hao R, Smith PB, Cai J, Simons MN, Hatzakis E, Maranas CD, Gonzalez FJ, Patterson AD. Farnesoid X Receptor Signaling Shapes the Gut Microbiota and Controls Hepatic Lipid Metabolism. mSystems. 2016 Sep-Oct; 1(5). PMID: 27822554.
      Citations: 48     Fields:    
    25. Arora K, Cheng J, Nichols RA. Nicotinic Acetylcholine Receptors Sensitize a MAPK-linked Toxicity Pathway on Prolonged Exposure to ?-Amyloid. J Biol Chem. 2015 Aug 28; 290(35):21409-20. PMID: 26139609.
      Citations: 9     Fields:    Translation:AnimalsCells
    26. Zhang L, Hatzakis E, Nichols RG, Hao R, Correll J, Smith PB, Chiaro CR, Perdew GH, Patterson AD. Metabolomics Reveals that Aryl Hydrocarbon Receptor Activation by Environmental Chemicals Induces Systemic Metabolic Dysfunction in Mice. Environ Sci Technol. 2015 Jul 07; 49(13):8067-77. PMID: 26023891.
      Citations: 30     Fields:    Translation:Animals
    27. Berry MJ, Astern J, Bellinger F, Brampton C, Cann R, Gerschenson M, Haymer D, James NG, Jameson DM, LeSaux O, Hoffmann PR, Nichols R, Pitts M, Seale L, Seifried S, Stokes AJ, Todorovic C. Medical school hotline: the research mission of the cell and molecular biology department and program at the john a. Burns school of medicine. Hawaii J Med Public Health. 2015 Apr; 74(4):150-3. PMID: 25954603.
      Citations:    Fields:    Translation:Humans
    28. Zhang L, Nichols RG, Correll J, Murray IA, Tanaka N, Smith PB, Hubbard TD, Sebastian A, Albert I, Hatzakis E, Gonzalez FJ, Perdew GH, Patterson AD. Persistent Organic Pollutants Modify Gut Microbiota-Host Metabolic Homeostasis in Mice Through Aryl Hydrocarbon Receptor Activation. Environ Health Perspect. 2015 Jul; 123(7):679-88. PMID: 25768209.
      Citations: 105     Fields:    Translation:AnimalsCells
    29. Jiang C, Xie C, Li F, Zhang L, Nichols RG, Krausz KW, Cai J, Qi Y, Fang ZZ, Takahashi S, Tanaka N, Desai D, Amin SG, Albert I, Patterson AD, Gonzalez FJ. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J Clin Invest. 2015 Jan; 125(1):386-402. PMID: 25500885.
      Citations: 296     Fields:    Translation:HumansAnimals
    30. Berry MJ, Cann R, Haymer D, Hoffmann P, Jameson D, LeSaux O, Nichols R, Seifried S, Stokes A, Todorovic C. Medical school hotline: The educational mission of the cell and molecular biology department and program at the John A. Burns School of Medicine. Hawaii J Med Public Health. 2014 Nov; 73(11):362-4. PMID: 25414807.
      Citations:    Fields:    Translation:Humans
    31. Lawrence JL, Tong M, Alfulaij N, Sherrin T, Contarino M, White MM, Bellinger FP, Todorovic C, Nichols RA. Regulation of presynaptic Ca2+, synaptic plasticity and contextual fear conditioning by a N-terminal ?-amyloid fragment. J Neurosci. 2014 Oct 22; 34(43):14210-8. PMID: 25339735.
      Citations: 27     Fields:    Translation:AnimalsCells
    32. Arora K, Alfulaij N, Higa JK, Panee J, Nichols RA. Impact of sustained exposure to ?-amyloid on calcium homeostasis and neuronal integrity in model nerve cell system expressing a4?2 nicotinic acetylcholine receptors. J Biol Chem. 2013 Apr 19; 288(16):11175-90. PMID: 23479730.
      Citations: 11     Fields:    Translation:HumansAnimalsCells
    33. Pitts MW, Raman AV, Hashimoto AC, Todorovic C, Nichols RA, Berry MJ. Deletion of selenoprotein P results in impaired function of parvalbumin interneurons and alterations in fear learning and sensorimotor gating. Neuroscience. 2012 Apr 19; 208:58-68. PMID: 22640876.
      Citations: 30     Fields:    Translation:AnimalsCells
    34. Nichols RA. Serotonin, presynaptic 5-HT3 receptors and synaptic plasticity in the developing cerebellum. J Physiol. 2011 Nov 01; 589(Pt 21):5019-20. PMID: 22042545.
      Citations: 2     Fields:    Translation:AnimalsCells
    35. Tong M, Arora K, White MM, Nichols RA. Role of key aromatic residues in the ligand-binding domain of alpha7 nicotinic receptors in the agonist action of beta-amyloid. J Biol Chem. 2011 Sep 30; 286(39):34373-81. PMID: 21828053.
      Citations: 22     Fields:    Translation:AnimalsCells
    36. Yang K, Buhlman L, Khan GM, Nichols RA, Jin G, McIntosh JM, Whiteaker P, Lukas RJ, Wu J. Functional nicotinic acetylcholine receptors containing a6 subunits are on GABAergic neuronal boutons adherent to ventral tegmental area dopamine neurons. J Neurosci. 2011 Feb 16; 31(7):2537-48. PMID: 21325521.
      Citations: 50     Fields:    Translation:AnimalsCells
    37. Khan GM, Tong M, Jhun M, Arora K, Nichols RA. beta-Amyloid activates presynaptic alpha7 nicotinic acetylcholine receptors reconstituted into a model nerve cell system: involvement of lipid rafts. Eur J Neurosci. 2010 Mar; 31(5):788-96. PMID: 20374280.
      Citations: 26     Fields:    Translation:AnimalsCells
    38. Dougherty JJ, Nichols RA. Cross-regulation between colocalized nicotinic acetylcholine and 5-HT3 serotonin receptors on presynaptic nerve terminals. Acta Pharmacol Sin. 2009 Jun; 30(6):788-94. PMID: 19498419.
      Citations: 10     Fields:    Translation:AnimalsCells
    39. Mehta TK, Dougherty JJ, Wu J, Choi CH, Khan GM, Nichols RA. Defining pre-synaptic nicotinic receptors regulated by beta amyloid in mouse cortex and hippocampus with receptor null mutants. J Neurochem. 2009 Jun; 109(5):1452-8. PMID: 19457164.
      Citations: 12     Fields:    Translation:AnimalsCells
    40. Dougherty JJ, Wu J, Mehta TK, Brown B, Nichols RA. Chronic nicotine alters nicotinic receptor-induced presynaptic Ca2+ responses in isolated nerve terminals. Neurochem Res. 2008 Jun; 33(6):1106-12. PMID: 18095155.
      Citations: 3     Fields:    Translation:AnimalsCells
    41. Nichols RA, Dengler AF, Nakagawa EM, Bashkin M, Paul BT, Wu J, Khan GM. A constitutive, transient receptor potential-like Ca2+ influx pathway in presynaptic nerve endings independent of voltage-gated Ca2+ channels and Na+/Ca2+ exchange. J Biol Chem. 2007 Dec 07; 282(49):36102-11. PMID: 17928293.
      Citations: 11     Fields:    Translation:AnimalsCells
    42. Wu J, Khan GM, Nichols RA. Dopamine release in prefrontal cortex in response to beta-amyloid activation of alpha7 * nicotinic receptors. Brain Res. 2007 Nov 28; 1182:82-9. PMID: 17935702.
      Citations: 20     Fields:    Translation:Animals
    43. Wu J, Dougherty JJ, Nichols RA. Dopamine receptor regulation of Ca2+ levels in individual isolated nerve terminals from rat striatum: comparison of presynaptic D1-like and D2-like receptors. J Neurochem. 2006 Jul; 98(2):481-94. PMID: 16805841.
      Citations: 13     Fields:    Translation:AnimalsCells
    44. Dougherty JJ, Wu J, Nichols RA. Beta-amyloid regulation of presynaptic nicotinic receptors in rat hippocampus and neocortex. J Neurosci. 2003 Jul 30; 23(17):6740-7. PMID: 12890766.
      Citations: 90     Fields:    Translation:AnimalsCells
    45. van Hooft JA, Dougherty JJ, Endeman D, Nichols RA, Wadman WJ. Gabapentin inhibits presynaptic Ca(2+) influx and synaptic transmission in rat hippocampus and neocortex. Eur J Pharmacol. 2002 Aug 09; 449(3):221-28. PMID: 12167463.
      Citations: 21     Fields:    Translation:AnimalsCells
    46. Nayak SV, Dougherty JJ, McIntosh JM, Nichols RA. Ca(2+) changes induced by different presynaptic nicotinic receptors in separate populations of individual striatal nerve terminals. J Neurochem. 2001 Mar; 76(6):1860-70. PMID: 11259504.
      Citations: 10     Fields:    Translation:AnimalsCells
    47. Rond? P, Nichols RA. Postsynaptic target regulates functional responses induced by 5-HT3 serotonin receptors on axonal varicosities of NG108-15 hybrid neuroblastoma cells. Neuroscience. 2001; 102(4):979-87. PMID: 11182259.
      Citations: 3     Fields:    Translation:AnimalsCells
    48. Rond? P, Dougherty JJ, Nichols RA. Functional IP3- and ryanodine-sensitive calcium stores in presynaptic varicosities of NG108-15 (rodent neuroblastoma x glioma hybrid) cells. J Physiol. 2000 Dec 01; 529 Pt 2:307-19. PMID: 11101642.
      Citations: 7     Fields:    Translation:AnimalsCells
    49. Nayak SV, Rond? P, Spier AD, Lummis SC, Nichols RA. Nicotinic receptors co-localize with 5-HT(3) serotonin receptors on striatal nerve terminals. Neuropharmacology. 2000 Oct; 39(13):2681-90. PMID: 11044738.
      Citations: 19     Fields:    Translation:Animals
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