Positive allosteric modulation of the α7 nicotinic acetylcholine receptor as a treatment for cognitive deficits after traumatic brain injury

Autoři: David J. Titus aff001;  Timothy Johnstone aff002;  Nathan H. Johnson aff001;  Sidney H. London aff001;  Meghana Chapalamadugu aff001;  Derk Hogenkamp aff002;  Kelvin W. Gee aff002;  Coleen M. Atkins aff001
Působiště autorů: Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, United States of America aff001;  Department of Pharmacology, School of Medicine, University of California Irvine, Irvine, California, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223180


Cognitive impairments are a common consequence of traumatic brain injury (TBI). The hippocampus is a subcortical structure that plays a key role in the formation of declarative memories and is highly vulnerable to TBI. The α7 nicotinic acetylcholine receptor (nAChR) is highly expressed in the hippocampus and reduced expression and function of this receptor are linked with cognitive impairments in Alzheimer’s disease and schizophrenia. Positive allosteric modulation of α7 nAChRs with AVL-3288 enhances receptor currents and improves cognitive functioning in naïve animals and healthy human subjects. Therefore, we hypothesized that targeting the α7 nAChR with the positive allosteric modulator AVL-3288 would enhance cognitive functioning in the chronic recovery period of TBI. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury or sham surgery. At 3 months after recovery, animals were treated with vehicle or AVL-3288 at 30 min prior to cue and contextual fear conditioning and the water maze task. Treatment of TBI animals with AVL-3288 rescued learning and memory deficits in water maze retention and working memory. AVL-3288 treatment also improved cue and contextual fear memory when tested at 24 hr and 1 month after training, when TBI animals were treated acutely just during fear conditioning at 3 months post-TBI. Hippocampal atrophy but not cortical atrophy was reduced with AVL-3288 treatment in the chronic recovery phase of TBI. AVL-3288 application to acute hippocampal slices from animals at 3 months after TBI rescued basal synaptic transmission deficits and long-term potentiation (LTP) in area CA1. Our results demonstrate that AVL-3288 improves hippocampal synaptic plasticity, and learning and memory performance after TBI in the chronic recovery period. Enhancing cholinergic transmission through positive allosteric modulation of the α7 nAChR may be a novel therapeutic to improve cognition after TBI.

Klíčová slova:

Atrophy – Cognitive impairment – Drug therapy – Fear conditioning – Hippocampus – Memory – Surgical and invasive medical procedures – Nicotinic acetylcholine receptors


1. Frieden TR, Houry D, Baldwin G. Report to Congress on traumatic brain injury in the United States: epidemiology and rehabilitation. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, Atlanta, GA. 2015.

2. Zaloshnja E, Miller T, Langlois JA, Selassie AW. Prevalence of long-term disability from traumatic brain injury in the civilian population of the United States, 2005. J Head Trauma Rehabil. 2008;23(6):394–400. doi: 10.1097/01.HTR.0000341435.52004.ac 19033832

3. Sigurdardottir S, Andelic N, Roe C, Jerstad T, Schanke AK. Post-concussion symptoms after traumatic brain injury at 3 and 12 months post-injury: a prospective study. Brain Inj. 2009;23(6):489–97. doi: 10.1080/02699050902926309 19484622

4. Bigler ED, Anderson CV, Blatter DD. Temporal lobe morphology in normal aging and traumatic brain injury. Am J Neuroradiol. 2002;23(2):255–66. 11847051

5. Tate DF, Bigler ED. Fornix and hippocampal atrophy in traumatic brain injury. Learn Mem. 2000;7(6):442–6. 11112803

6. Wheaton P, Mathias JL, Vink R. Impact of pharmacological treatments on cognitive and behavioral outcome in the postacute stages of adult traumatic brain injury: a meta-analysis. J Clin Psychopharmacol. 2011;31(6):745–57. doi: 10.1097/JCP.0b013e318235f4ac 22020351

7. Drever BD, Riedel G, Platt B. The cholinergic system and hippocampal plasticity. Behav Brain Res. 2011;221(2):505–14. doi: 10.1016/j.bbr.2010.11.037 21130117

8. Arciniegas DB. Cholinergic dysfunction and cognitive impairment after traumatic brain injury. Part 1: the structure and function of cerebral cholinergic systems. J Head Trauma Rehabil. 2011;26(1):98–101. doi: 10.1097/HTR.0b013e31820516cb 21209567

9. Lombardo S, Maskos U. Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment. Neuropharm. 2015;96(Pt B):255–62.

10. Schneider LS, Mangialasche F, Andreasen N, Feldman H, Giacobini E, Jones R, et al. Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014. J Intern Med. 2014;275(3):251–83. doi: 10.1111/joim.12191 24605808

11. Wada E, Wada K, Boulter J, Deneris E, Heinemann S, Patrick J, et al. Distribution of α2, α3, α4, and -β2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: a hybridization histochemical study in the rat. J Comp Neurol. 1989;284(2):314–35. doi: 10.1002/cne.902840212 2754038

12. Seguela P, Wadiche J, Dineley-Miller K, Dani JA, Patrick JW. Molecular cloning, functional properties, and distribution of rat brain α7: a nicotinic cation channel highly permeable to calcium. J Neurosci. 1993;13(2):596–604. 7678857

13. Fabian-Fine R, Skehel P, Errington ML, Davies HA, Sher E, Stewart MG, et al. Ultrastructural distribution of the α7 nicotinic acetylcholine receptor subunit in rat hippocampus. J Neurosci. 2001;21(20):7993–8003. 11588172

14. McQuiston AR. Acetylcholine release and inhibitory interneuron activity in hippocampal CA1. Front Synaptic Neurosci. 2014;6:20. doi: 10.3389/fnsyn.2014.00020 25278874

15. Radcliffe KA, Dani JA. Nicotinic stimulation produces multiple forms of increased glutamatergic synaptic transmission. J Neurosci. 1998;18(18):7075–83. 9736631

16. Orr-Urtreger A, Goldner FM, Saeki M, Lorenzo I, Goldberg L, De Biasi M, et al. Mice deficient in the α7 neuronal nicotinic acetylcholine receptor lack α-bungarotoxin binding sites and hippocampal fast nicotinic currents. J Neurosci. 1997;17(23):9165–71. 9364063

17. Ma L, Turner D, Zhang J, Wang Q, Wang M, Shen J, et al. Deficits of synaptic functions in hippocampal slices prepared from aged mice null α7 nicotinic acetylcholine receptors. Neurosci Lett. 2014;570:97–101. doi: 10.1016/j.neulet.2014.04.018 24769321

18. Titus DJ, Furones C, Kang Y, Atkins CM. Age-dependent alterations in cAMP signaling contribute to synaptic plasticity deficits following traumatic brain injury. Neuroscience. 2013;231:182–94. doi: 10.1016/j.neuroscience.2012.12.002 23238576

19. Titus DJ, Sakurai A, Kang Y, Furones C, Jergova S, Santos R, et al. Phosphodiesterase inhibition rescues chronic cognitive deficits induced by traumatic brain injury. J Neurosci. 2013;33(12):5216–26. doi: 10.1523/JNEUROSCI.5133-12.2013 23516287

20. Nakauchi S, Sumikawa K. Endogenously released ACh and exogenous nicotine differentially facilitate long-term potentiation induction in the hippocampal CA1 region of mice. Eur J Neurosci. 2012;35(9):1381–95. doi: 10.1111/j.1460-9568.2012.08056.x 22462479

21. Lagostena L, Trocme-Thibierge C, Morain P, Cherubini E. The partial α7 nicotine acetylcholine receptor agonist S 24795 enhances long-term potentiation at CA3-CA1 synapses in the adult mouse hippocampus. Neuropharm. 2008;54(4):676–85.

22. Arciniegas DB. Cholinergic dysfunction and cognitive impairment after traumatic brain injury. Part 2: evidence from basic and clinical investigations. J Head Trauma Rehabil. 2011;26(4):319–23. doi: 10.1097/HTR.0b013e31821ebfb3 21734513

23. Kelso ML, Oestreich JH. Traumatic brain injury: central and peripheral role of α7 nicotinic acetylcholine receptors. Curr Drug Targets. 2012;13(5):631–6. doi: 10.2174/138945012800398964 22300031

24. Shin SS, Dixon CE. Alterations in cholinergic pathways and therapeutic strategies targeting cholinergic system after traumatic brain injury. J Neurotrauma. 2015;32(19):1429–40. doi: 10.1089/neu.2014.3445 25646580

25. Dixon CE, Bao J, Bergmann JS, Johnson KM. Traumatic brain injury reduces hippocampal high-affinity [3H]choline uptake but not extracellular choline levels in rats. Neurosci Lett. 1994;180(2):127–30. doi: 10.1016/0304-3940(94)90503-7 7700564

26. Dixon CE, Flinn P, Bao J, Venya R, Hayes RL. Nerve growth factor attenuates cholinergic deficits following traumatic brain injury in rats. Exp Neurol. 1997;146(2):479–90. doi: 10.1006/exnr.1997.6557 9270059

27. Donat CK, Schuhmann MU, Voigt C, Nieber K, Deuther-Conrad W, Brust P. Time-dependent alterations of cholinergic markers after experimental traumatic brain injury. Brain Res. 2008;1246:167–77. doi: 10.1016/j.brainres.2008.09.059 18848922

28. Valiyaveettil M, Alamneh Y, Oguntayo S, Wei Y, Wang Y, Arun P, et al. Regional specific alterations in brain acetylcholinesterase activity after repeated blast exposures in mice. Neurosci Lett. 2012;506(1):141–5. doi: 10.1016/j.neulet.2011.10.067 22079491

29. Verbois SL, Scheff SW, Pauly JR. Time-dependent changes in rat brain cholinergic receptor expression after experimental brain injury. J Neurotrauma. 2002;19(12):1569–85. doi: 10.1089/089771502762300238 12542858

30. Hoffmeister PG, Donat CK, Schuhmann MU, Voigt C, Walter B, Nieber K, et al. Traumatic brain injury elicits similar alterations in α7 nicotinic receptor density in two different experimental models. Neuromolecular Med. 2011;13(1):44–53. doi: 10.1007/s12017-010-8136-4 20857232

31. Schmidt RH, Grady MS. Loss of forebrain cholinergic neurons following fluid-percussion injury: implications for cognitive impairment in closed head injury. J Neurosurg. 1995;83(3):496–502. doi: 10.3171/jns.1995.83.3.0496 7666229

32. Ostberg A, Virta J, Rinne JO, Oikonen V, Luoto P, Nagren K, et al. Cholinergic dysfunction after traumatic brain injury: preliminary findings from a PET study. Neurology. 2011;76(12):1046–50. doi: 10.1212/WNL.0b013e318211c1c4 21422456

33. Salmond CH, Chatfield DA, Menon DK, Pickard JD, Sahakian BJ. Cognitive sequelae of head injury: involvement of basal forebrain and associated structures. Brain. 2005;128(Pt 1):189–200. doi: 10.1093/brain/awh352 15548553

34. Verbois SL, Hopkins DM, Scheff SW, Pauly JR. Chronic intermittent nicotine administration attenuates traumatic brain injury-induced cognitive dysfunction. Neuroscience. 2003;119(4):1199–208. doi: 10.1016/s0306-4522(03)00206-9 12831873

35. Dixon CE, Ma X, Marion DW. Effects of CDP-choline treatment on neurobehavioral deficits after TBI and on hippocampal and neocortical acetylcholine release. J Neurotrauma. 1997;14(3):161–9. doi: 10.1089/neu.1997.14.161 9104933

36. Guseva MV, Hopkins DM, Scheff SW, Pauly JR. Dietary choline supplementation improves behavioral, histological, and neurochemical outcomes in a rat model of traumatic brain injury. J Neurotrauma. 2008;25(8):975–83. doi: 10.1089/neu.2008.0516 18665805

37. Pike BR, Hamm RJ, Temple MD, Buck DL, Lyeth BG. Effect of tetrahydroaminoacridine, a cholinesterase inhibitor, on cognitive performance following experimental brain injury. J Neurotrauma. 1997;14(12):897–905. doi: 10.1089/neu.1997.14.897 9475371

38. Shaw KE, Bondi CO, Light SH, Massimino LA, McAloon RL, Monaco CM, et al. Donepezil is ineffective in promoting motor and cognitive benefits after controlled cortical impact injury in male rats. J Neurotrauma. 2013;30(7):557–64. doi: 10.1089/neu.2012.2782 23227953

39. Scremin OU, Norman KM, Roch M, Holschneider DP, Scremin AM. Acetylcholinesterase inhibition interacts with training to reverse spatial learning deficits after cortical impact injury. J Neurotrauma. 2012;29(15):2457–64. doi: 10.1089/neu.2012.2465 22738336

40. Walker W, Seel R, Gibellato M, Lew H, Cornis-Pop M, Jena T, et al. The effects of Donepezil on traumatic brain injury acute rehabilitation outcomes. Brain Inj. 2004;18(8):739–50. doi: 10.1080/02699050310001646224 15204315

41. Zhang L, Plotkin RC, Wang G, Sandel ME, Lee S. Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury. Arch Phys Med Rehabil. 2004;85(7):1050–5. doi: 10.1016/j.apmr.2003.10.014 15241749

42. Tenovuo O, Alin J, Helenius H. A randomized controlled trial of rivastigmine for chronic sequels of traumatic brain injury-what it showed and taught? Brain Inj. 2009;23(6):548–58. doi: 10.1080/02699050902926275 19484628

43. Yu TS, Kim A, Kernie SG. Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis. PLoS One. 2015;10(2):e0118793. doi: 10.1371/journal.pone.0118793 25714524

44. Noble JM, Hauser WA. Effects of rivastigmine on cognitive function in patients with traumatic brain injury. Neurology. 2007;68(20):1749. doi: 10.1212/01.wnl.0000266745.86958.ce 17502565

45. de la Tremblaye PB, Bondi CO, Lajud N, Cheng JP, Radabaugh HL, Kline AE. Galantamine and environmental enrichment enhance cognitive recovery after experimental traumatic brain injury but do not confer additional benefits when combined. J Neurotrauma. 2017;34(8):1610–22. doi: 10.1089/neu.2016.4790 27806662

46. Njoku I, Radabaugh HL, Nicholas MA, Kutash LA, O'Neil DA, Marshall IP, et al. Chronic treatment with galantamine rescues reversal learning in an attentional set-shifting test after experimental brain trauma. Exp Neurol. 2019;315:32–41. doi: 10.1016/j.expneurol.2019.01.019 30711647

47. Ng HJ, Whittemore ER, Tran MB, Hogenkamp DJ, Broide RS, Johnstone TB, et al. Nootropic α7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators. Proc Natl Acad Sci U S A. 2007;104(19):8059–64. doi: 10.1073/pnas.0701321104 17470817

48. Hogenkamp DJ, Ford-Hutchinson TA, Li WY, Whittemore ER, Yoshimura RF, Tran MB, et al. Design, synthesis, and activity of a series of arylpyrid-3-ylmethanones as type I positive allosteric modulators of α7 nicotinic acetylcholine receptors. J Med Chem. 2013;56(21):8352–65. doi: 10.1021/jm400704g 24098954

49. Klann E, Roberson ED, Knapp LT, Sweatt JD. A role for superoxide in protein kinase C activation and induction of long-term potentiation. J Biol Chem. 1998;273(8):4516–22. doi: 10.1074/jbc.273.8.4516 9468506

50. Rutten K, Misner DL, Works M, Blokland A, Novak TJ, Santarelli L, et al. Enhanced long-term potentiation and impaired learning in phosphodiesterase 4D-knockout (PDE4D-/-) mice. Eur J Neurosci. 2008;28(3):625–32. doi: 10.1111/j.1460-9568.2008.06349.x 18702734

51. Gee KW, Olincy A, Kanner R, Johnson L, Hogenkamp D, Harris J, et al. First in human trial of a type I positive allosteric modulator of α7-nicotinic acetylcholine receptors: pharmacokinetics, safety, and evidence for neurocognitive effect of AVL-3288. J Psychopharmacol. 2017;31(4):434–41. doi: 10.1177/0269881117691590 28196430

52. Titus DJ, Wilson NM, Alcazar O, Calixte DA, Dietrich WD, Gurney ME, et al. A negative allosteric modulator of PDE4D enhances learning after traumatic brain injury. Neurobiol Learn Mem. 2018;148:38–49. doi: 10.1016/j.nlm.2017.12.008 29294383

53. Fujiki M, Kubo T, Kamida T, Sugita K, Hikawa T, Abe T, et al. Neuroprotective and antiamnesic effect of donepezil, a nicotinic acetylcholine-receptor activator, on rats with concussive mild traumatic brain injury. J Clin Neuro. 2008;15(7):791–6.

54. Verbois SL, Scheff SW, Pauly JR. Chronic nicotine treatment attenuates α7 nicotinic receptor deficits following traumatic brain injury. Neuropharm. 2003;44(2):224–33.

55. Bramlett HM, Dietrich WD. Quantitative structural changes in white and gray matter 1 year following traumatic brain injury in rats. Acta Neuropathol (Berl). 2002;103(6):607–14.

56. Thomsen MS, El-Sayed M, Mikkelsen JD. Differential immediate and sustained memory enhancing effects of α7 nicotinic receptor agonists and allosteric modulators in rats. PLoS One. 2011;6(11):e27014. doi: 10.1371/journal.pone.0027014 22096516

57. Targowska-Duda KM, Wnorowski A, Budzynska B, Jozwiak K, Biala G, Arias HR. The positive allosteric modulator of α7 nicotinic acetylcholine receptors, 3-furan-2-yl-N-p-tolyl-acrylamide, enhances memory processes and stimulates ERK1/2 phosphorylation in mice. Behav Brain Res. 2016;302:142–51. doi: 10.1016/j.bbr.2016.01.002 26778787

58. Timmermann DB, Gronlien JH, Kohlhaas KL, Nielsen EO, Dam E, Jorgensen TD, et al. An allosteric modulator of the α7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J Pharmacol Exp Ther. 2007;323(1):294–307. doi: 10.1124/jpet.107.120436 17625074

59. Almeida-Suhett CP, Prager EM, Pidoplichko V, Figueiredo TH, Marini AM, Li Z, et al. Reduced GABAergic inhibition in the basolateral amygdala and the development of anxiety-like behaviors after mild traumatic brain injury. PLoS One. 2014;9(7):e102627. doi: 10.1371/journal.pone.0102627 25047645

60. Robinson SE, Ryland JE, Martin RM, Gyenes CA, Davis TR. The effects of morphine and traumatic brain injury on central cholinergic neurons. Brain Res. 1989;503(1):32–7. doi: 10.1016/0006-8993(89)91699-5 2611656

61. Palmer CP, Metheny HE, Elkind JA, Cohen AS. Diminished amygdala activation and behavioral threat response following traumatic brain injury. Exp Neurol. 2016;277:215–26. doi: 10.1016/j.expneurol.2016.01.004 26791254

62. Kelso ML, Wehner JM, Collins AC, Scheff SW, Pauly JR. The pathophysiology of traumatic brain injury in α7 nicotinic cholinergic receptor knockout mice. Brain Res. 2006;1083(1):204–10. doi: 10.1016/j.brainres.2006.01.127 16545784

63. Johnstone TB, Gu Z, Yoshimura RF, Villegier AS, Hogenkamp DJ, Whittemore ER, et al. Allosteric modulation of related ligand-gated ion channels synergistically induces long-term potentiation in the hippocampus and enhances cognition. J Pharmacol Exp Ther. 2011;336(3):908–15. doi: 10.1124/jpet.110.176255 21159751

64. Ji D, Lape R, Dani JA. Timing and location of nicotinic activity enhances or depresses hippocampal synaptic plasticity. Neuron. 2001;31(1):131–41. doi: 10.1016/s0896-6273(01)00332-4 11498056

65. Bitner RS, Bunnelle WH, Anderson DJ, Briggs CA, Buccafusco J, Curzon P, et al. Broad-spectrum efficacy across cognitive domains by α7 nicotinic acetylcholine receptor agonism correlates with activation of ERK1/2 and CREB phosphorylation pathways. J Neurosci. 2007;27(39):10578–87. doi: 10.1523/JNEUROSCI.2444-07.2007 17898229

66. Zhang L, Xie JW, Yang J, Cao YP. Tyrosine phosphatase STEP61 negatively regulates amyloid β-mediated ERK/CREB signaling pathways via α7 nicotinic acetylcholine receptors. J Neurosci Res. 2013;91(12):1581–90. doi: 10.1002/jnr.23263 24123152

67. Norris CM, Scheff SW. Recovery of afferent function and synaptic strength in hippocampal CA1 following traumatic brain injury. J Neurotrauma. 2009;26(12):2269–78. doi: 10.1089/neu.2009.1029 19604098

68. Titus DJ, Wilson NM, Freund JE, Carballosa MM, Sikah KE, Furones C, et al. Chronic cognitive dysfunction after traumatic brain injury is improved with a phosphodiesterase 4B inhibitor. J Neurosci. 2016;36(27):7095–108. doi: 10.1523/JNEUROSCI.3212-15.2016 27383587

69. Atkins CM, Falo MC, Alonso OF, Bramlett HM, Dietrich WD. Deficits in ERK and CREB activation in the hippocampus after traumatic brain injury. Neurosci Lett. 2009;459(2):52–6. doi: 10.1016/j.neulet.2009.04.064 19416748

70. Maier DL, Hill G, Ding M, Tuke D, Einstein E, Gurley D, et al. Pre-clinical validation of a novel alpha-7 nicotinic receptor radiotracer, [3H]AZ11637326: target localization, biodistribution and ligand occupancy in the rat brain. Neuropharm. 2011;61(1–2):161–71.

71. Nirogi R, Kandikere V, Bhyrapuneni G, Saralaya R, Muddana N, Komarneni P. Methyllycaconitine: a non-radiolabeled ligand for mapping α7 neuronal nicotinic acetylcholine receptors—in vivo target localization and biodistribution in rat brain. J Pharmacol Toxicol Methods. 2012;66(1):22–8. doi: 10.1016/j.vascn.2012.05.003 22609758

72. Han ZY, Le Novere N, Zoli M, Hill JA Jr., Champtiaux N, Changeux JP. Localization of nAChR subunit mRNAs in the brain of Macaca mulatta. Eur J Neurosci. 2000;12(10):3664–74. doi: 10.1046/j.1460-9568.2000.00262.x 11029636

73. Breese CR, Adams C, Logel J, Drebing C, Rollins Y, Barnhart M, et al. Comparison of the regional expression of nicotinic acetylcholine receptor α7 mRNA and [125I]-α-bungarotoxin binding in human postmortem brain. J Comp Neurol. 1997;387(3):385–98. doi: 10.1002/(sici)1096-9861(19971027)387:3<385::aid-cne5>3.0.co;2-x 9335422

74. Ramlackhansingh AF, Brooks DJ, Greenwood RJ, Bose SK, Turkheimer FE, Kinnunen KM, et al. Inflammation after trauma: microglial activation and traumatic brain injury. Ann Neurol. 2011;70(3):374–83. doi: 10.1002/ana.22455 21710619

75. Gatson JW, Simpkins JW, Uteshev VV. High therapeutic potential of positive allosteric modulation of α7 nAChRs in a rat model of traumatic brain injury: proof-of-concept. Brain Res Bull. 2015;112:35–41. doi: 10.1016/j.brainresbull.2015.01.008 25647232

76. Munro G, Hansen R, Erichsen H, Timmermann D, Christensen J, Hansen H. The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat. Br J Pharmacol. 2012;167(2):421–35. doi: 10.1111/j.1476-5381.2012.02003.x 22536953

77. Shytle RD, Mori T, Townsend K, Vendrame M, Sun N, Zeng J, et al. Cholinergic modulation of microglial activation by α7 nicotinic receptors. J Neurochem. 2004;89(2):337–43. doi: 10.1046/j.1471-4159.2004.02347.x 15056277

78. Pavlov VA, Parrish WR, Rosas-Ballina M, Ochani M, Puerta M, Ochani K, et al. Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway. Brain Behav Immun. 2009;23(1):41–5. doi: 10.1016/j.bbi.2008.06.011 18639629

79. Dash PK, Zhao J, Kobori N, Redell JB, Hylin MJ, Hood KN, et al. Activation of α7 cholinergic nicotinic receptors reduce blood-brain barrier permeability following experimental traumatic brain injury. J Neurosci. 2016;36(9):2809–18. doi: 10.1523/JNEUROSCI.3197-15.2016 26937017

80. Zhao J, Hylin MJ, Kobori N, Hood KN, Moore AN, Dash PK. Post-injury administration of galantamine reduces traumatic brain injury pathology and improves outcome. J Neurotrauma. 2018;35(2):362–74. doi: 10.1089/neu.2017.5102 29088998

81. Tenovuo O. Central acetylcholinesterase inhibitors in the treatment of chronic traumatic brain injury-clinical experience in 111 patients. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(1):61–7. doi: 10.1016/j.pnpbp.2004.10.006 15610946

82. Ballesteros J, Guemes I, Ibarra N, Quemada JI. The effectiveness of donepezil for cognitive rehabilitation after traumatic brain injury: a systematic review. J Head Trauma Rehabil. 2008;23(3):171–80. doi: 10.1097/01.HTR.0000319935.99837.96 18520431

83. McAllister TW, Zafonte R, Jain S, Flashman LA, George MS, Grant GA, et al. Randomized placebo-controlled trial of methylphenidate or galantamine for persistent emotional and cognitive symptoms associated with PTSD and/or traumatic brain injury. Neuropsychopharm. 2016;41(5):1191–8.

84. Koola MM. Galantamine and memantine combination for cognition: Enough or more than enough to translate from murines and macaques to men with schizophrenia? Asian J Psychiatr. 2019;42:115–8. doi: 10.1016/j.ajp.2017.11.008 29150389

85. Matsuzono K, Hishikawa N, Ohta Y, Yamashita T, Deguchi K, Nakano Y, et al. Combination therapy of cholinesterase inhibitor (donepezil or galantamine) plus memantine in the Okayama memantine study. J Alzheimers Dis. 2015;45(3):771–80. doi: 10.3233/JAD-143084 25624417

86. Tsoi KK, Chan JY, Leung NW, Hirai HW, Wong SY, Kwok TC. Combination therapy showed limited superiority over monotherapy for Alzheimer disease: a meta-analysis of 14 randomized trials. J Am Med Dir Assoc. 2016;17(9):863 e1–8.

87. Shao ZQ. Comparison of the efficacy of four cholinesterase inhibitors in combination with memantine for the treatment of Alzheimer's disease. Int J Clin Exp Med. 2015;8(2):2944–8. 25932260

88. Koola MM. Galantamine-memantine combination for cognitive impairments due to electroconvulsive therapy, traumatic brain injury, and neurologic and psychiatric disorders: kynurenic acid and mismatch negativity target engagement. Prim Care Companion CNS Disord. 2018;20(2).

89. Navakkode S, Korte M. Cooperation between cholinergic and glutamatergic receptors are essential to induce BDNF-dependent long-lasting memory storage. Hippocampus. 2012;22(2):335–46. doi: 10.1002/hipo.20902 21254300

90. Massey KA, Zago WM, Berg DK. BDNF up-regulates α7 nicotinic acetylcholine receptor levels on subpopulations of hippocampal interneurons. Mol Cell Neurosci. 2006;33(4):381–8. doi: 10.1016/j.mcn.2006.08.011 17029981

91. Mihalak KB, Carroll FI, Luetje CW. Varenicline is a partial agonist at α4β2 and a full agonist at α7 neuronal nicotinic receptors. Mol Pharmacol. 2006;70(3):801–5. doi: 10.1124/mol.106.025130 16766716

92. Smith RC, Amiaz R, Si TM, Maayan L, Jin H, Boules S, et al. Varenicline effects on smoking, cognition, and psychiatric symptoms in schizophrenia: a double-blind randomized trial. PLoS One. 2016;11(1):e0143490. doi: 10.1371/journal.pone.0143490 26730716

93. Kim SY, Choi SH, Rollema H, Schwam EM, McRae T, Dubrava S, et al. Phase II crossover trial of varenicline in mild-to-moderate Alzheimer's disease. Dement Geriatr Cogn Disord. 2014;37(3–4):232–45. doi: 10.1159/000355373 24247022

94. Lewis AS, van Schalkwyk GI, Bloch MH. Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and human studies. Prog Neuropsychopharmacol Biol Psychiatry. 2017;75:45–53. doi: 10.1016/j.pnpbp.2017.01.001 28065843

95. Haber M, Abdel Baki SG, Grin'kina NM, Irizarry R, Ershova A, Orsi S, et al. Minocycline plus N-acetylcysteine synergize to modulate inflammation and prevent cognitive and memory deficits in a rat model of mild traumatic brain injury. Exp Neurol. 2013;249:169–77. doi: 10.1016/j.expneurol.2013.09.002 24036416

96. Abdel Baki SG, Schwab B, Haber M, Fenton AA, Bergold PJ. Minocycline synergizes with N-acetylcysteine and improves cognition and memory following traumatic brain injury in rats. PLoS One. 2010;5(8):e12490. doi: 10.1371/journal.pone.0012490 20824218

97. Koola MM. Antipsychotic-minocycline-acetylcysteine combination for positive, cognitive, and negative symptoms of schizophrenia. Asian J Psychiatr. 2019;40:100–2. doi: 10.1016/j.ajp.2019.02.007 30776665

98. Hernandez CM, Gearhart DA, Parikh V, Hohnadel EJ, Davis LW, Middlemore ML, et al. Comparison of galantamine and donepezil for effects on nerve growth factor, cholinergic markers, and memory performance in aged rats. J Pharmacol Exp Ther. 2006;316(2):679–94. doi: 10.1124/jpet.105.093047 16214877

99. Barnes CA, Meltzer J, Houston F, Orr G, McGann K, Wenk GL. Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors. Neuroscience. 2000;99(1):17–23. doi: 10.1016/s0306-4522(00)00180-9 10924948

100. Christensen DZ, Mikkelsen JD, Hansen HH, Thomsen MS. Repeated administration of α7 nicotinic acetylcholine receptor (nAChR) agonists, but not positive allosteric modulators, increases α7 nAChR levels in the brain. J Neurochem. 2010;114(4):1205–16. doi: 10.1111/j.1471-4159.2010.06845.x 20533993

101. Werkheiser JL, Sydserff S, Hubbs SJ, Ding M, Eisman MS, Perry D, et al. Ultra-low exposure to α-7 nicotinic acetylcholine receptor partial agonists elicits an improvement in cognition that corresponds with an increase in α-7 receptor expression in rodents: implications for low dose clinical efficacy. Neuroscience. 2011;186:76–87. doi: 10.1016/j.neuroscience.2011.04.033 21550383

102. Reid RT, Sabbagh MN. Effects of donepezil treatment on rat nicotinic acetylcholine receptor levels in vivo and in vitro. J Alzheimers Dis. 2003;5(6):429–36. 14757932

103. Guseva MV, Hopkins DM, Pauly JR. An autoradiographic analysis of rat brain nicotinic receptor plasticity following dietary choline modification. Pharmacol Biochem Behav. 2006;84(1):26–34. doi: 10.1016/j.pbb.2006.04.002 16753203

104. Giniatullin R, Nistri A, Yakel JL. Desensitization of nicotinic ACh receptors: shaping cholinergic signaling. Trends Neurosci. 2005;28(7):371–8. doi: 10.1016/j.tins.2005.04.009 15979501

105. Hurst RS, Hajos M, Raggenbass M, Wall TM, Higdon NR, Lawson JA, et al. A novel positive allosteric modulator of the α7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. J Neurosci. 2005;25(17):4396–405. doi: 10.1523/JNEUROSCI.5269-04.2005 15858066

Článek vyšel v časopise


2019 Číslo 10
Nejčtenější tento týden