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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.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    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. 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.
    2. Roberts JP, Stokoe SA, Sathler MF, Nichols RA, Kim S. Selective coactivation of a7- and a4ß2-nicotinic acetylcholine receptors reverses beta-amyloid-induced synaptic dysfunction. J Biol Chem. 2021 Jan-Jun; 296:100402. PMID: 33571523.
      Citations: 5     Fields:    Translation:HumansAnimalsCells
    3. Tan X, Liang Z, Li Y, Zhi Y, Yi L, Bai S, Forest KH, Nichols RA, Dong Y, Li QX. Isoorientin, a GSK-3ß 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: 2     Fields:    Translation:AnimalsCells
    4. 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: 1     Fields:    Translation:HumansAnimalsCells
    5. 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: 5     Fields:    Translation:Animals
    6. Forest KH, Nichols RA. Assessing Neuroprotective Agents for Aß-Induced Neurotoxicity. Trends Mol Med. 2019 08; 25(8):685-695. PMID: 31248781.
      Citations: 5     Fields:    Translation:HumansAnimalsCells
    7. 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: 22     Fields:    Translation:AnimalsCells
    8. 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: 93     Fields:    Translation:AnimalsCells
    9. 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: 11     Fields:    Translation:AnimalsCells
    10. Kabbani N, Nichols RA. Beyond the Channel: Metabotropic Signaling by Nicotinic Receptors. Trends Pharmacol Sci. 2018 04; 39(4):354-366. PMID: 29428175.
      Citations: 32     Fields:    Translation:HumansAnimalsCells
    11. 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
    12. Forest KH, Alfulaij N, Arora K, Taketa R, Sherrin T, Todorovic C, Lawrence JLM, Yoshikawa GT, Ng HL, Hruby VJ, Nichols RA. Protection against ß-amyloid neurotoxicity by a non-toxic endogenous N-terminal ß-amyloid fragment and its active hexapeptide core sequence. J Neurochem. 2018 01; 144(2):201-217. PMID: 29164616.
      Citations: 9     Fields:    Translation:AnimalsCells
    13. 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: 15     Fields:    Translation:Animals
    14. Arora K, Cheng J, Nichols RA. Nicotinic Acetylcholine Receptors Sensitize a MAPK-linked Toxicity Pathway on Prolonged Exposure to ß-Amyloid. J Biol Chem. 2015 Aug 28; 290(35):21409-20. PMID: 26139609.
      Citations: 7     Fields:    Translation:AnimalsCells
    15. 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
    16. 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: 77     Fields:    Translation:AnimalsCells
    17. 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: 203     Fields:    Translation:HumansAnimals
    18. 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
    19. 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 ß-amyloid fragment. J Neurosci. 2014 Oct 22; 34(43):14210-8. PMID: 25339735.
      Citations: 21     Fields:    Translation:AnimalsCells
    20. Arora K, Alfulaij N, Higa JK, Panee J, Nichols RA. Impact of sustained exposure to ß-amyloid on calcium homeostasis and neuronal integrity in model nerve cell system expressing a4ß2 nicotinic acetylcholine receptors. J Biol Chem. 2013 Apr 19; 288(16):11175-90. PMID: 23479730.
      Citations: 9     Fields:    Translation:HumansAnimalsCells
    21. 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: 27     Fields:    Translation:AnimalsCells
    22. 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
    23. 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: 18     Fields:    Translation:AnimalsCells
    24. 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: 46     Fields:    Translation:AnimalsCells
    25. 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: 24     Fields:    Translation:AnimalsCells
    26. 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: 7     Fields:    Translation:AnimalsCells
    27. 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: 10     Fields:    Translation:AnimalsCells
    28. 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
    29. 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: 10     Fields:    Translation:AnimalsCells
    30. 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: 18     Fields:    Translation:Animals
    31. 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: 11     Fields:    Translation:AnimalsCells
    32. 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: 79     Fields:    Translation:AnimalsCells
    33. 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: 17     Fields:    Translation:AnimalsCells
    34. 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: 8     Fields:    Translation:AnimalsCells
    35. Rondé 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: 2     Fields:    Translation:AnimalsCells
    36. Rondé 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
    37. Nayak SV, Rondé 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: 17     Fields:    Translation:Animals
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