Subscribe to RSS
DOI: 10.1055/s-0029-1224138
© Georg Thieme Verlag KG Stuttgart · New York
Neuroprotective and Neurotoxic Effects of Nicotine
Publication History
received 27.11.2008
revised 05.03.2009
accepted 16.03.2009
Publication Date:
18 November 2009 (online)
Abstract
The interest in the action of nicotine in the central nervous system (CNS) has significantly increased during the past 15 years. This is due in part to the growing importance of nicotine addiction and its consequences in terms of life quality and costs for public health systems in industrialized countries and, on the other hand, to the significantly higher prevalence of tobacco consumption in patients with psychiatric disorders. The actual data indicate opposite effects of nicotine in the CNS. Nicotine seems to have, at the same time, positive, neuroprotective as well as negative, neurotoxic effects. This suggests that nicotine's action is complex, probably involving different neuronal circuits influencing each other through complicated interactions. In the present review we summarize the most important results of experiments about nicotinic neuroprotection and neurotoxicity in humans and animals. Initially, we illustrate well known modifications of cholinergic transmission during physiological (normal aging) and pathological neurodegeneration. In the second part of the paper we describe neuroprotective and neurotoxic effects of nicotine also mentioning the underlying molecular mechanisms.
References
- 1 Abreu-Villaça Y, Seidler FJ, Slotkin TA. Does prenatal nicotine exposure sensitize the brain to nicotine-induced neurotoxicity in adolescence?. Neuropsychopharmacology. 2004; 29 1440-1450
- 2 Abreu-Villaça Y, Seidler FJ, Tate CA. et al . Prenatal nicotine exposure alters the response to nicotine administration in adolescence: effects on cholinergic systems during exposure and withdrawal. Neuropsychopharmacology. 2004; 29 879-890
- 3 Abrous DN, Adriani W, Montaron M-F. et al . Nicotine self-administration impairs hippocampal plasticity. J Neurosci. 2002; 22 3656-3662
- 4 Akaike A, Tamura Y, Yokota T. et al . Nicotine-induced protection of cultured cortical neurons against N-methyl-d-aspartate receptor-mediated glutamate cytotoxicity. Brain Res. 1994; 644 181-187
- 5 Araujo DM, Lapchak PA, Meaney MJ. et al . Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: relationship to presynaptic cholinergic markers and binding sites. J Neurosci. 1990; 10 3069-3078
- 6 Arias E, Ales E, Gabilan NH. et al . Galantamine prevents apoptosis induced by beta-amyloid and thapsigargin: involvement of nicotinic acetylcholine receptors. Neuropharmacology. 2004; 46 103-114
- 7 Aubert I, Araujo DM, Cécyre D. et al . Comparative alteration of nicotinic and muscarinic binding sites in Alzheimer's and Parkinson's diseases. J Neurochem. 1992; 58 529-541
- 8 Behmand RA, Harik SI. Nicotine enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. J Neurochem. 1992; 58 776-779
- 9 Belluardo N, Blum M, Mudò G. et al . Acute intermittent nicotine treatment produces regional increases of basic fibroblast growth factor messenger RNA and protein in the tel- and diencephalons of the rat. Neuroscience. 1998; 83 723-740
- 10 Belluardo N, Mudò G, Blum M. et al . The nicotinic acetylcholine receptor agonist (±)-epibatidine increases FGF-2 mRNA and protein levels in the rat brain. Mol Brain Res. 1999; 74 98-110
- 11 Belluardo N, Mudò G, Blum M. et al . Nicotine-induced FGF-2 mRNA in rat brain is preserved during aging. Neurobiol Aging. 2004; 25 1333-1342
- 12 Belluardo N, Mudò G, Caniglia G. et al . The nicotinic acetylcholine receptor agonist ABT-594 increases FGF-2 expression in various rat brain regions. NeuroReport. 1999; 10 3909-3913
- 13 Berger F, Gage FH, Vijayaraghavan S. Nicotinic receptor-induced apoptotic cell death of hippocampal progenitor cells. J Neurosci. 1998; 18 6871-6881
- 14 Berner J, Ringstedt T, Brodin E. et al . Prenatal exposure to nicotine affects substance p and preprotachykinin-A mRNA levels in newborn rat. Pediatr Res. 2008; 64 621-624
- 15 Birtsch C, Wevers A, Traber J. et al . Expression of alpha 4-1 and alpha 5 nicotinic cholinoceptor mRNA in the aging rat cerebral cortex. Neurobiol Aging. 1997; 18 335-342
- 16 Blum M, Wu G, Mudò G. et al . Chronic continuous infusion of (−)-nicotine reduces basic fibroblast growth factor messenger RNA levels in the ventral midbrain of the intact but not of the 6-hydroxydopamine-lesioned rat. Neuroscience. 1996; 70 169-177
- 17 Bordia T, Parameswaran N, Fan H. et al . Partial recovery of striatal nicotinic receptors in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys with chronic oral nicotine. J Pharmacol Exp Ther. 2006; 319 285-292
- 18 Borlongan CV, Shytle RD, Ross SD. et al . Nicotine protects against systemic kainic acid-induced excitotoxic effects. Exp Neurol. 1995; 136 261-265
- 19 Broide RS, Leslie FM. The alpha7 nicotinic acetylcholine receptor in neuronal plasticity. Mol Neurobiol. 1999; 20 1-16
- 20 Caldarone BJ, Duman CH, Picciotto MR. Fear conditioning and latent inhibition in mice lacking the high-affinity subclass of nicotinic acetylcholine receptors in the brain. Neuropharmacology. 2000; 39 2779-2784
- 21 Carlson J, Noguchi K, Ellison G. Nicotine produces selective degeneration in the medial habenula and fasciculus retroflexus. Brain Res. 2001; 906 127-134
- 22 Carlson NG, Bacchi A, Rogers SW. et al . Nicotine blocks TNF-alpha-mediated neuroprotection to NMDA by an alpha-bungarotoxin-sensitive pathway. J Neurobiol. 1998; 35 29-36
- 23 Chen WJ, King KA, Lee RE. et al . Effects of nicotine exposure during prenatal or perinatal period on cell numbers in adult rat hippocampus and cerebellum: A stereology study. Life Sci. 2006; 79 2221-2227
- 24 Cormier A, Morin C, Zini R. et al . In vitro effects of nicotine on mitochondrial respiration and superoxide anion generation. Brain Res. 2001; 900 72-79
- 25 Cormier A, Morin C, Zini R. et al . Nicotine protects rat brain mitochondria against experimental injuries. Neuropharm. 2003; 44 642-652
- 26 Costa G, Abin-Carriquiry JA, Dajas F. Nicotine prevents striatal dopamine loss produced by 6-hydroxydopamine lesion in the substantia nigra. Brain Res. 2001; 888 336-342
- 27 Court JA, Johnson M, Religa D. et al . Attenuation of Aß deposition in the entorhinal cortex of normal elderly individuals associated with tobacco smoking. Neuropathol Applied Neurobiol. 2005; 31 522-535
- 28 Court JA, Lloyd S, Johnson M. et al . Nicotinic and muscarinic cholinergic receptor binding in the human hippocampal formation during development and aging. Dev Brain Res. 1997; 101 93-105
- 29 Dajas-Bailador FA, Lima PA, Wonnacott S. The alpha7 nicotinic acetylcholine receptor subtype mediates nicotine protection against NMDA excitotoxicity in primary hippocampal cultures through a Ca++ dependent mechanism. Neuropharmacology. 2000; 39 2799-2807
- 30 Decker MW. The effects of aging on hippocampal and cortical projections of the forebrain cholinergic system. Brain Res. 1987; 434 423-438
- 31 Delbro D, Westerlund A, Björklund U. et al . In inflammatory reactive astrocytes co-cultured with brain endothelial cells nicotine-evoked Ca(2+) transients are attenuated due to interleukin-1beta release and rearrangement of actin filaments. Neuroscience. 2009; Ahead of print.
- 32 Dineley KT, Westerman M, Bui D. et al . Beta-amyloid activates the mitogen-activated protein kinase cascade via hippocampal alpha7 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimer's disease. J Neurosci. 2001; 21 4125-4133
- 33 Donnelly-Roberts DL, Xue IC, Arneric SP. et al . In vitro neuroprotective properties of the novel cholinergic channel activator (ChCA), ABT-418. Brain Res. 1996; 719 36-44
- 34 Duncan JR, Randall LL, Belliveau RA. et al . The effect of maternal smoking an drinking during pregnancy upon (3)H-nicotine receptor brainstem binding in infants dying of the sudden infant death syndrome: initial observations in a high risk population. Brain Pathol. 2008; 18 21-31
- 35 Dwyer JB, Broide RS, Leslie FM. Nicotine and brain development. Birt Defects Res C Embryo Today. 2008; 84 30-44
- 36 Egea J, Rosa AO, Sobrado M. et al . Neuroprotection afforded by nicotine against oxygen and glucose deprivation in hippocampal slices is lost in alpha7 nicotinic receptor knockout mice. Neuroscience. 2007; 145 866-872
- 37 Eugenín J, Otárola M, Bravo E. et al . Prenatal to early postnatal nicotine exposure impairs central chemoreception and modifies breathing pattern in mouse neonates: a probable link to sudden infant death syndrome. J Neurosci. 2008; 28 13907-13917
- 38 Ferchmin PA, Hao J, Perez D. et al . Tobacco cembranoids protect the function of acute hippocampal slices against NMDA by a mechanism mediated by alpha4beta2 nicotinic receptors. J Neurosci Res. 2005; 82 631-641
- 39 Ferrari R, Frasoldati A, Leo G. et al . Changes in nicotinic acetylcholine receptor subunit mRNAs and nicotinic binding in spontaneously hypertensive stroke prone rats. Neurosci Lett. 1999; 277 169-172
- 40 French SJ, Humby T, Horner CH. et al . Hippocampal neurotrophin and trk receptor mRNA levels are altered by local administration of nicotine, carbachol, and pilocarpine. Mol Brain Res. 1999; 67 124-136
- 41 Fuxe K, Janson AM, Jansson A. et al . Chronic nicotine treatment increases dopamine levels and reduces dopamine utilization in substantia nigra and in surviving forebrain dopamine nerve terminal system after a partial di-mesencephalic hemitransection. Naunyn-Schm Arch Pharmacol. 1990; 341 171-181
- 42 Gahring LC, Persiyanov K, Rogers SW. Mouse strain-specific changes in nicotinic receptor expression with age. Neurobiol Aging. 2005; 26 973-980
- 43 Gallinat J, Schubert F. Regional cerebral glutamate concentrations and chronic tobacco consumption. Pharmacopsychiatry. 2007; 40 64-67
- 44 Gioanni Y, Rougeot C, Clarke PBS. et al . Nicotinic receptors in the rat prefrontal cortex: increase in glutamate release and facilitation of mediodorsal thalamo-cortical transmission. Eur J Neurosci. 1999; 11 18-30
- 45 Gotti C, Fornasari D, Clementi F. Human neuronal nicotinic receptors. Prog Neurobiol. 1997; 53 199-237
- 46 Guan ZZ, Miao H, Tian JY. et al . Suppressed expression of nicotinic acetylcholine receptors by nanomolar beta-amyloid peptides in PC12 cells. J Neural Trans. 2001; 108 1417-1433
- 47 Guan ZZ, Yu WF, Nordberg A. Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells. Neurochem Int. 2003; 43 243-249
- 48 Guan ZZ, Zhang X, Ravid R. et al . Decreased protein levels of nicotinic receptor subunits in the hippocampus and temporal cortex of patients with Alzheimer's disease. J Neurochem. 2000; 74 237-243
- 49 Gunes T, Koklu E, Gunes I. et al . Influence of maternal nicotine exposure on neonatal rat oxidant-antioxidant system and effect of ascorbic acid supplementation. Hum Exp Toxicol. 2008; 27 781-786
- 50 Gutala R, Wang J, Hwang YY. et al . Nicotine modulates expression of amyloid precursor protein and amyloid precursor-like protein 2 in mouse brain and in SH-SY5Y neuroblastoma cells. Brain Res. 2006; 1093 12-19
- 51 Hadjiconstantinou M, Hubble JP, Wemlinger TA. et al . Enhanced MPTP neurotoxicity after treatment with isoflurophate or cholinergic agonists. J Pharmacol Exp Therap. 1994; 270 639-644
- 52 Heading CE. Conus peptides and neuroprotection. Curr Opin Invest Drugs. 2002; 3 915-920
- 53 Heath CJ, Picciotto MR. Nicotine-induced plasticity during development: modulation of the cholinergic system and long-term consequences for circuits involved in attention and sensory processing. Neuropharmacology. 2009; 56 ((Suppl 1)) 254-262
- 54 Hejmadi MV, Bailador F, Barns SM. et al . Neuroprotection by nicotine against hypoxia-induced apoptosis in cortical cultures involves activation of multiple nicotinic acetylcholine receptor subtypes. Mol Cell Neurosci. 2003; 24 779-786
- 55 Hellström-Lindahl E, Court JA. Nicotinic acetylcholine receptors during prenatal development and brain pathology in human aging. Behav Brain Res. 2000; 113 159-168
- 56 Hong DP, Fink AL, Uversky VN. Smoking and Parkinson's disease: Does nicotine affect alpha-synuclein fibrillation?. Biochim Biophys Acta. 2009; 1794 282-290
- 57 Hory-Lee F, Frank E. The nicotinic blocking agents d-tubocurare and alpha-bungarotoxin save motoneurons from naturally occurring death in the absence of neuromuscular blockade. J Neurosci. 1995; 15 6453-6460
- 58 Howard LA, Ahliwalia JS, Lin SK. et al . Brain CYP2E1 is induced by nicotine and ethanol in rat and is higher in smokers and alcoholics. Br J Pharmacol. 2003; 138 1376-1386
- 59 Huang LZ, Abbott LC, Winzer-Serhan UH. Effects of chronic neonatal nicotine exposure on nicotinic acetylcholine receptor binding, cell death and morphology inn hippocampus and cerebellum. Neuroscience. 2007; 146 1854-1868
- 60 Huang LZ, Winzer-Serhan UH. Nicotine regulates mRNA expression of feeding peptides in the arcuate nucleus in neonatal pups. Dev Neurobiol. 2007; 67 363-377
- 61 Jacobsen LK, Krystal JH, Menci WE. et al . Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers. Biol Psychiatry. 2005; 57 56-66
- 62 Janson AM, Fuxe K, Goldstein M. Differential effects of acute and chronic nicotine treatment on MPTP-(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced degeneration of nigrostriatal dopamine neurons in the black mouse. Clin Invest. 1992; 70 232-238
- 63 Janson AM, Hedlund PB, Fuxe K. et al . Chronic nicotine treatment counteracts dopamine D2 receptor upregulation induced by a partial meso-diencephalic hemitransection in the rat. Brain Res. 1994; 655 25-32
- 64 Janson AM, Moller A. Chronic nicotine treatment counteracts nigral cell loss induced by a partial mesodiencephalic hemitransection: an analysis of the total number and mean volume of neurons and glia in substantia nigra of the male rat. Neuroscience. 1993; 57 931-941
- 65 Jeyarasasingam G, Tompkins L, Quik M. Stimulation of non-alpha 7 nicotinic receptors partially protects dopaminergic neurons from 1-methyl-4-phenylpyridinium-induced toxicity in culture. Neuroscience. 2002; 109 275-285
- 66 Jonnala RR, Buccafusco JJ. Relationship between the increased cell surface alpha7 nicotinic receptor expression and neuroprotection induced by several nicotinic receptor agonists. J Neurosci Res. 2001; 66 565-572
- 67 Kaneko S, Maeda T, Kume T. et al . Nicotine protects cultured cortical neurons against glutamate-induced cytotoxicity via alpha7-neuronal receptors and neuronal. CNS receptors. 1997; 765 135-140
- 68 Kasa P, Rakonczay Z, Gulya K. The cholinergic system in Alzheimer's disease. Prog Neurobiol. 1997; 52 511-535
- 69 Khwaja M, McCormack A, McIntosh JM. et al . Nicotine partially protects against paraquat-induced nigrostriatal damage in mice; link to alpha6beta2* nAChRs. J Neurochem. 2007; 100 180-190
- 70 Kihara T, Shimohama S, Sawada H. et al . Alpha 7 nicotinic receptors transduces signals to phosphatidylinositol 3-kinase to block Aß-amyloid-induced neurotoxicity. J Biol Chem. 2001; 276 13541-13546
- 71 Kihara T, Shimohama S, Sawada H. et al . Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity. Ann Neurol. 1997; 42 159-163
- 72 Kihara T, Shimohama S, Urushitani M. et al . Stimulation of alpha-4-beta-2 nicotinic acetylcholine receptors inhibits beta-amyloid toxicity. Brain Res. 1998; 792 331-334
- 73 Laudenbach V, Medja F, Zoli M. et al . Selective activation of central subtypes of the nicotinic acetylcholine receptor has opposite effects on neonatal excitotoxic brain injuries. FASEB J. 2002; 16 423-425
- 74 Lavezzi AM, Mauri M, Mecchia D. et al . Developmental alterations of the prefrontal cerebral cortex in sudden unexplained perinatal and infant deaths. J Perinat Med. 2009; Ahead of print
- 75 Lee MY, Chen L, Toborek M. Nicotine attenuates iNOS expression and contributes to neuroprotection in a compressive model of spinal cord injury. J Neurosci Res. 2008; 87 937-947
- 76 Levin ED. Nicotinic receptor subtypes and cognitive function. J Neurobiol. 2002; 53 633-640
-
77 Levin ED, Slotkin TA. Developmental neurotoxicity of nicotine. In: Slikker W Jr, Chang LW, editors
Handbook of developmental neurotoxicology . San Diego: Academic press 1998: p587-615 - 78 Li MD, Kane JK, Matta SG. et al . Nicotine enhances the biosynthesis and secretion of transthyretin from the choroid plexus in rats: implications for beta-amyloid formation. J Neurosci. 2000; 20 1318-1323
- 79 Li Y, Meyer EM, Walker DW. et al . Alpha7 nicotinic receptor activation inhibits ethanol-induced mitochondrial dysfunction, cytochrome c release and neurotoxicity in primary rat hippocampal neuronal cultures. J Neurochem. 2002; 81 853-858
- 80 Linert W, Herlinger E, Jameson RF. et al . Dopamine, 6-hydroxydopamine, iron, and dioxygen – their mutual interactions and possible implication in the development of Parkinson's disease. Biochim Biophys Acta. 1996; 1316 160-168
- 81 Liu Q, Kawai H, Berg DK. Beta-amyloid peptide blocks the response of alpha 7-containing nicotinic receptors on hippocampal neurons. Proc Natl Acad Sci USA. 2001; 98 4734-4739
- 82 Liu Q, Zhang J, Zhu H. et al . Dissecting the signalling pathway of nicotine-mediated neuroprotection in a mouse Alzheimer disease model. FASEB J. 2007; 21 61-73
- 83 Liu Q, Zhao B. Nicotine attenuates beta-amyloid peptide-induced neurotoxicity, free radical and calcium accumulation in hippocampal neuronal cultures. Br J Pharmacol. 2004; 141 746-754
- 84 Machaalani R, Waters KA, Tinworth KD. Effects of postnatal nicotine exposure on apoptotic markers in the developing piglet brain. Neuroscience. 2005; 132 325-333
- 85 Maggio R, Riva M, Vaglini F. et al . Nicotine prevents experimental parkinsonism in rodents and induces striatal increase of neurotrophic factors. J Neurochem. 1998; 71 2439-2446
- 86 Maggio R, Riva M, Vaglini F. et al . Striatal increase of neurotrophic factors as a mechanism of nicotine protection in experimental parkinsonism. J Neural Transm. 1997; 104 1113-1123
- 87 Marin P, Maus M, Desagher S. et al . Nicotine protects cultured striatal neurons against N-methyl-D-aspartate receptor-mediated neurotoxicity. NeuroReport. 1994; 5 1977-1980
- 88 Marrero MB, Bencherif M. Convergence of alpha 7 nicotinic acetylcholine receptor-activated pathways for anti-apoptosis and anti-inflammation: central role for JAK2 activation of STAT3 and NF-kappaB. Brain Res. 2009; 1256 1-7
- 89 Marutle A, Warpman U, Bogdanovic N. et al . Regional distribution of subtypes of nicotinic receptors in human brain and effect of aging studied by (±)-[3H]epibatidine. Brain Res. 1998; 801 143-149
- 90 Matarredona ER, Santiago M, Venero JL. et al . Group II metabotropic glutamate receptor activation protects striatal dopaminergic nerve terminals against MPP+-induced neurotoxicity along with brain-derived neurotrophic factor induction. J Neurochem. 2001; 76 351-360
- 91 Maurice T, Lockhart BP, Privat A. Amnesia induced in mice by centrally administered beta-amyloid peptides involves cholinergic dysfunction. Brain Res. 1996; 706 181-193
- 92 McFarland BJ, Seidler FJ, Slotkin TA. Inhibition of DNA synthesis in neonatal rat brain regions caused by acute nicotine administration. Brain Res Dev Brain Res. 1991; 58 223-229
- 93 Messi ML, Renganathan M, Grigorenko E. et al . Activation of alpha7 nicotinic acetylcholine receptor promotes survival of spinal cord motoneurons. FEBS Lett. 1997; 411 32-38
- 94 Meyer EM, King MA, Meyers C. Neuroprotective effects of 2,4-dimethoxybenzylidene anabaseine (DMXB) and tetrahydroaminoacridine (THA) in neocortices of nucleus basalis lesions rats. Brain Res. 1998; 786 252-254
- 95 Miksys S, Hoffmann E, Tyndale RF. Regional and cellular induction of nicotine metabolizing CYP2B1 in rat brain by chronic nicotine treatment. Biochem Pharmacol. 2000; 59 1501-1511
- 96 Miksys S, Tyndale RF. Nicotine induces brain CYP enzymes: relevance to Parkinson's disease. J Neural Transm Suppl. 2006; 70 177-180
- 97 Minana MD, Montoliu C, Llansola M. et al . Nicotine prevents glutamate-induced proteolysis of the microtubule-associated protein MAP-2 and glutamate neurotoxicity in primary cultures of cerebellar neurons. Neuropharmacology. 1998; 37 847-857
- 98 Mobascher A, Winterer G. The molecular and cellular neurobiology of nicotine abuse in schizophrenia. Pharmacopsychiatry. 2008; 41 ((Suppl)) S51-S59
- 99 Mousavi M, Hellström-Lindahl E. Nicotinic receptor agonists and antagonists increase sAPPalpha secretion and decrease Aß levels in vitro. Neurochem Int. 2008; Ahead of print
- 100 Mudò G, Belluardo N, Fuxe K. Nicotinic receptor agonists as neuroprotective/neurotrophic drugs. Progress in molecular mechanisms. J Neural Transm. 2007; 114 135-147
- 101 Mulle C, Choquet D, Korn H. et al . Calcium influx through nicotinic receptor in rat central neurons – its relevance to cellular regulation. Neuron. 1992; 8 135-143
- 102 Muneoka K, Nakatsu T, Fuji J. et al . Prenatal administration of nicotine results in dopaminergic alterations in the neocortex. Neurotoxicol Teratol. 1999; 21 603-609
- 103 Muneoka K, Ogawa T, Kamei K. et al . Prenatal nicotine exposure affects the development of the central serotonergic system as well as the dopaminergic system in rat offspring: involvement of route of drug administration. Brain Res Dev Brain Res. 1997; 102 117-126
- 104 Nagele RG, D’Andrea MR, Anderson WJ. et al . Intracellular accumulation of beta-amyloid (1–42) in neurons is facilitated by the alpha7 nicotinic acetylcholine receptor in Alzheimer's disease. Neuroscience. 2002; 110 199-211
- 105 Nanri M, Kasahara N, Yamamoto J. et al . GTS-21, a nicotinic agonist, protects against neocortical neuronal cell loss induced by the nucleus basalis magnocellularis lesion in rats. Jpn J Pharmacol. 1997; 74 285-289
- 106 Nanri M, Miyake H, Murakami Y. et al . GTS-21, a nicotinic agonist, attenuates multiple infarctions and cognitive deficit caused by permanent occlusion of bilateral common carotid arteries in rats. Jpn J Pharmacol. 1998; 78 463-469
- 107 Navarro HA, Seidler FJ, Schwartz RD. et al . Prenatal exposure to nicotine impairs nervous system development at a dose which does not affect viability of growth. Brain Res Bull. 1989; 23 187-192
- 108 Newman MB, Arendash GW, Shytle RD. et al . Nicotine's oxidative and antioxidant properties in CNS. Life Sci. 2002; 71 2807-2820
- 109 Nordberg A. Neuroreceptor changes in Alzheimer disease. Cerebrovasc Brain Metab Rev. 1992; 4 303-328
- 110 Nordberg A, Hellström-Lindahl E, Lee M. et al . Chronic nicotine treatment reduces beta-amyloidosis in the brain of a mouse model of Alzheimer's disease (APPsw). J Neurochem. 2002; 81 655-658
- 111 Nordberg A, Lilja A, Lundqvist H. et al . Tacrine restores cholinergic nicotinic receptors and glucose metabolism in Alzheimer patients as visualized by Positron Emission Tomography. Neurobiol Aging. 1992; 13 747-758
- 112 Nordberg A, Lundqvist H, Hartvig P. et al . Imaging of nicotinic and muscarinic receptors in Alzheimer's disease: effect of tacrine treatment. Dement Geriatr Cogn Disord. 1997; 8 78-84
- 113 Nordberg A, Zhang XA, Fredriksson A. Neonatal nicotine exposure induces permanent changes in brain nicotinic receptors and behaviour in adult mice. Brain Res Dev Brain Res. 1991; 63 201-207
- 114 Obata T, Aomine M, Inada T. et al . Nicotine suppresses 1-methyl-4-phenylpyridinium ion-induced hydroxyl radical generation in rat striatum. Neurosci Lett. 2002; 330 122-124
- 115 Oddo S, Caccamo A, Green KN. et al . Chronic nicotine administration exacerbates tau pathology in a transgenic model of Alzheimer's disease. Proc Natl Acad Sci USA. 2005; 102 3046-3051
- 116 Ohnishi M, Katsuki H, Takagi M. et al . Long-term treatment with nicotine suppresses neurotoxicity of, and microglial activation by, thrombin in cortico-striatal slice cultures. Eur J Pharmacol. 2009; 602 288-293
- 117 Okamoto M, Kita T, Okuda H. et al . Effects of aging on acute toxicity of nicotine in rats. Pharmacol Toxicol. 1994; 75 1-6
- 118 O’Neill AB, Morgan SJ, Brioni JD. Histological and behavioural protection by (−)-nicotine against quinolinic acid-induced neurodegeneration in the hippocampus. Neurobiol Learn Mem. 1998; 69 46-64
- 119 Ono K, Hirohata M, Yamada M. Anti-fibrillogenic and fibril-destabilizing activity of nicotine in vitro: Implications for the prevention and therapeutics of Lewy body diseases. Exp Neurol. 2007; 205 414-424
- 120 Ono K, Hasegawa K, Yamada M. et al . Nicotine breaks down preformed Alzheimer's beta-amyloid fibrils in vitro. Biol Psych. 2002; 52 880-886
- 121 Orr-Urtreger A, Broide RS, Kasten MR. et al . Mice homozygous for the L250T mutation in the alpha 7 nicotinic acetylcholine receptor show increased neuronal apoptosis and die within 1 day of birth. J Neurochem. 2000; 74 2154-2166
- 122 Owman C, Fuxe K, Janson AM, Kahrstrom J. Studies of protective actions of nicotine on neuronal and vascular functions in the brain of rats: comparison between sympathetic noradrenergic and mesostriatal dopaminergic fiber systems, and the effect of a dopamine agonist. Prog Brain Res. 1989; 79 267-276
- 123 Parain K, Marchand V, Dumery B. et al . Nicotine, but not cotinine, partially protects dopaminergic neurons against MPTP-induced degeneration in mice. Brain Res. 2001; 890 347-350
- 124 Park MK, Loughlin SE, Leslie FM. Gestational nicotine-induced changes in adolescent neuronal activity. Brain Res. 2006; 1094 119-126
- 125 Pauly JR, Charriez CM, Guseva MV. et al . Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease. Ann N Y Acad Sci. 2004; 1035 316-334
- 126 Perry E, Martin-Ruiz C, Lee M. et al . Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases. Eur J Pharmacol. 2000; 393 215-222
- 127 Perry EK, Morris CM, Court JA. et al . Alteration in nicotine binding sites in Parkinson's disease, Lewy body dementia and Alzheimer's disease: possible index of early neuropathology. Neuroscience. 1995; 64 385-395
- 128 Pettit DL, Shao Z, Yakel JL. Beta-amyloid 1-42 peptide directly modulates nicotinic receptors in the rat hippocampal slice. J Neurosci. 2001; 21 1-5
- 129 Picciotto MR, Zoli M. Neuroprotection via nAChRs: the role of nAChRs in neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Front Biosci. 2008; 13 492-504
- 130 Picciotto MR, Zoli M. Nicotinic receptors in aging and dementia. J Neurobiol. 2002; 53 641-655
- 131 Picciotto MR, Zoli M, Léna C. et al . Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain. Nature. 1995; 374 65-67
- 132 Prendergast MA, Harris BR, Mayer S. et al . Chronic nicotine exposure reduces N-methyl-D-aspartate receptor-mediated damage in the hippocampus without altering calcium accumulation or extrusion: evidence of calbindin-D28 K overexpression. Neuroscience. 2001; 102 75-85
- 133 Prendergast MA, Harris BR, Mayer S. et al . Nicotine exposure reduces N-methyl-D-aspartate toxicity in the hippocampus: relation to distribution of the α7 nicotinic acetylcholine receptor subunit. Med Sci Monitor. 2001; 7 1153-1160
- 134 Pugh PC, Berg DK. Neuronal acetylcholine receptors that bind alpha-bungarotoxin mediate neurite retraction in a calcium-dependent manner. J Neurosci. 1994; 14 889-896
- 135 Quik M, Di Monte DA. Nicotine administration reduces striatal MPP levels in mice. Brain Res. 2001; 917 219-224
- 136 Quik M, Jeyarasasingam G. Nicotinic receptors and Parkinson's disease. Eur J Pharmacol. 2000; 393 223-230
- 137 Rathouz MM, Vijayaraghavan S, Berg DK. Elevation of intracellular calcium levels in neurons by nicotinic acetylcholine receptors. Mol Neurobiol. 1996; 12 117-131
- 138 Ravikumar R, Fugaccia I, Scheff SW. et al . Nicotine attenuates morphological deficits in a contusion model of spinal cord injury. J Neurotrauma. 2005; 22 240-251
- 139 Reid RT, Sabbagh MN, Corey-Bloom J. et al . Nicotinic receptor losses in dementia with Lewy bodies: comparisons with Alzheimer's disease. Neurobiol Aging. 2000; 21 741-746
- 140 Ren K, Puig V, Papke R. et al . Multiple calcium channels and kinases mediate alpha7 nicotinic receptor neuroprotection in PC12 cells. J Neurochem. 2005; 94 926-933
- 141 Renshaw GM, Dyson SE. Alpha-BTX lowers neuronal metabolism during the arrest of motoneurone apoptosis. NeuroReport. 1995; 6 284-288
- 142 Riljak V, Langmeier M. Nicotine an efficient tool of the neurobiological research today, the tool of treatment tomorrow?. Prague Med Rep. 2005; 106 329-348
- 143 Roberson MR, Harrell LE. Cholinergic activity and amyloid precursor protein metabolism. Brain Res Brain Res Rev. 1997; 25 50-69
- 144 Roceri M, Molteni R, Fumagalli F. et al . Stimulatory role of dopamine on fibroblast growth factor-2 expression in rat striatum. J Neurochem. 2001; 76 990-997
- 145 Rogers SW, Gahring LC, Collins AC. et al . Age-related changes in neuronal nicotinic acetylcholine receptor subunit alpha4 expression are modified by long-term nicotine administration. J Neurosci. 1998; 18 4825-4832
- 146 Rosa AO, Egea J, Gandía L. et al . Neuroprotection by nicotine in hippocampal slices subjected to oxygen-glucose deprivation: involvement of the alpha7nAChR subtype. J Mol Neurosci. 2006; 30 61-62
- 147 Rosato-Siri M, Cattaneo A, Cherubini E. Nicotine-induced enhancement of synaptic plasticity at CA3-CA1 synapses requires GABAergic interneurons in adult anti-NGF mice. J Physiol. 2006; 576 361-377
- 148 Roy TS, Andrews JE, Seidler FJ. et al . Nicotine evokes cell death in embryonic rat brain during neurulation. J Pharmacol Exp Ther. 1998; 287 1136-1144
- 149 Roy TS, Sabherwal U. Effects of prenatal nicotine exposure on the morphogenesis of somatosensory cortex. Neurotoxicol Teratol. 1994; 16 411-421
- 150 Roy TS, Sabherwal U. Effects of gestational nicotine exposure on hippocampal morphology. Neurotoxicol Teratol. 1998; 20 465-473
- 151 Rusted JM, Newhouse PA, Levin ED. Nicotinic treatment for degenerative neuropsychiatric disorders such as Alzheimer's disease and Parkinson's disease. Beh Brain Res. 2000; 113 121-129
- 152 Ryan RE, Ross SA, Drago J. et al . Dose-related neuroprotective effects of chronic nicotine in 6-hydroxydopamine treated rats, and loss of neuroprotection in alpha4 nicotinic receptor subunit knockout mice. Br J Pharmacol. 2001; 132 1650-1656
- 153 Salomon AR, Marcinowski KJ, Friedland RP. et al . Nicotine inhibits amyloid formation by the beta-peptide. Biochemistry. 1996; 35 13568-13578
- 154 Schochet TL, Bremer QZ, Brownfield MS. et al . The dendritically targeted protein Dendrin is induced by acute nicotine in cortical regions of adolescent rat brain. Eur J Neurosci. 2008; 28 1967-1979
- 155 Schulz DW, Kuchel GA, Zigmond RE. Decline in response to nicotine in aged rat striatum: correlation with a decrease in a subpopulation of nicotinic receptors. J Neurochem. 1993; 61 2225-2232
- 156 Semba J, Miyoshi R, Kito S. Nicotine protects against the dexamethasone potentiation of kainic acid-induced neurotoxicity in cultured hippocampal neurons. Brain Res. 1996; 735 335-338
- 157 Shaw S, Bencherif M, Marrero MB. Janus kinase 2, an early target of alpha 7 nicotinic acetylcholine receptor-mediated neuroprotection against Aß-(1–42) amyloid. J Biol Chem. 2002; 277 44920-44924
- 158 Shi FD, Piao WH, Kuo Yp. et al . Nicotinic attenuation of central nervous system inflammation and autoimmunity. J Immunol. 2009; 182 1730-1739
- 159 Shimohama S, Greenwald DL, Shafron DH. et al . Nicotinic alpha 7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage. Brain Res. 1998; 779 359-363
- 160 Shimohama S, Kihara T. Nicotinic receptor-mediated protection against beta-amyloid neurotoxicity. Biol Psychiatry. 2001; 49 233-239
- 161 Shin EJ, Chae JS, Jung ME. et al . Repeated intracerebroventricular infusion of nicotine prevents kainate-induced neurotoxicity by activating the alpha7 nicotinic acetylcholine receptor. Epilepsy Res. 2007; 73 292-298
- 162 Shytle RD, Borlongan CV, Sanberg PR. Nicotine blocks kainic acid-induced wet dog shakes in rats. Neuropsychopharm. 1995; 13 261-264
- 163 Singh S, Singh K, Patel S. et al . Nicotine and caffeine-mediated modulation in the expression of toxicant responsive genes and vesicular monoamino transporter-2 in 1-methyl 4 phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease phenotype in mouse. Brain Res. 2008; 1207 193-206
- 164 Sjak-Shie NN, Meyer EM. Effects of chronic nicotine and pilocarpine administration on neocortical neuronal density and [3H]GABA uptake in nucleus basalis lesioned rats. Brain Res. 1993; 624 295-298
- 165 Slotkin TA. Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates. Toxicol Appl Pharmacol. 2004; 198 132-151
- 166 Slotkin TA. Fetal nicotine or cocaine exposure: which one is worse?. J Pharmacol Exp Ther. 1998; 285 931-945
- 167 Slotkin TA. Nicotine and the adolescent brain: insights from an animal model. Neurotoxicol Teratol. 2002; 24 369-384
- 168 Slotkin TA, McCook EC, Seidler FJ. Cryptic brain cell injury caused by fetal nicotine exposure is associated with persistent elevations of c-fos protooncogene expression. Brain Res. 1997; 750 180-188
- 169 Slotkin TA, Pinkerton KE, Garofolo MC. et al . Perinatal exposure to environmental tobacco smoke induces adenylyl cyclase and alters receptor-mediated cell signalling in brain and hearth of neonatal rats. Brain Res. 2001; 898 73-81
- 170 Slotkin TA, Pinkerton KE, Seidler FJ. Perinatal environmental tobacco smoke exposure in rhesus monkeys: critical periods and regional selectivity for effects on brain cell development and lipid peroxidation. Environ Health Perspect. 2006; 114 34-39
- 171 Smith TD, Gallagher M, Leslie FM. Cholinergic binding sites in rat brain: analysis by age and cognitive status. Neurobiol Aging. 1995; 16 161-173
- 172 Socci DJ, Arendash GW. Chronic nicotine treatment prevents neuronal loss in neocortex resulting from nucleus basalis lesions in young adult and aged rats. Mol Chem Neuropathol. 1996; 27 285-305
- 173 Song YS, Park HJ, Kim SY. et al . Protective role of Bcl-2 on beta-amyloid-induced cell death of differentiated PC12 cells: reduction of NF-kappaB and p38 MAP kinase activation. Neurosci Res. 2004; 49 69-80
- 174 Soto-Otero R, Mendez-Alvarez E, Hermida-Ameijeiras A. et al . Effects of (−)-nicotine and (−)-cotinine on 6-hydroxydopamine-induced oxidative stress and neurotoxicity: relevance for Parkinson's disease. Biochem Pharmacol. 2002; 64 125-135
- 175 Stevens TR, Krueger SR, Fitzsimonds RM. et al . Neuroprotection by nicotine in mouse primary cortical cultures involves activation of calcineurin and L-type calcium channel inactivation. J Neurosci. 2003; 23 10093-10099
- 176 Sugaya K, Giacobini E, Chiappinelli VA. Nicotinic acetylcholine receptor subtypes in human frontal cortex: changes in Alzheimer's disease. J Neurosci Res. 1990; 27 349-359
- 177 Sun X, Liu Y, Hu G. et al . Protective effects of nicotine against glutamate-induced neurotoxicity in PC12 cells. Cell Mol Biol Lett. 2004; 9 409-422
- 178 Takeuchi H, Yanagida T, Inden M. et al . Nicotinic receptor stimulation protects nigral dopaminergic neurons in rotenone-induced Parkinson's disease models. J Neurosci Res. 2009; 87 576-585
- 179 Terzano S, Court JA, Fornasari D. et al . Expression of the alpha 3 nicotinic receptor subunit mRNA in aging and Alzheimer's disease. Mol Brain Res. 1998; 63 72-78
- 180 Tizabi Y, Al-Namaeh M, Manaye KF. et al . Protective effects of nicotine on ethanol-induced toxicity in cultured cerebellar granule cells. Neurotox Res. 2003; 3 315-321
- 181 Tizabi Y, Manaye KF, Smoot DT. et al . Nicotine inhibits ethanol-induced toxicity in cultured cerebral cortical cells. Neurotox Res. 2004; 6 311-316
- 182 Tizabi Y, Manaye KF, Taylor RE. Nicotine blocks ethanol-induced apoptosis in primary cultures of rat cerebral cortical and cerebellar granule cells. Neurotox Res. 2005; 7 319-322
- 183 Tohgi H, Utsugisawa K, Yoshimura M. et al . Age-related changes in nicotinic acetylcholine receptor subunits alpha4 and beta2 messenger RNA expression in postmortem human frontal cortex and hippocampus. Neurosci Lett. 1998; 245 139-142
- 184 Tohgi H, Utsugisawa K, Yoshimura M. et al . Alterations with aging and ischemia in nicotinic acetylcholine receptor subunits alpha4 and beta2 messenger RNA expression in post-mortem human putamen. Implications for susceptibility to parkinsonism. Brain Res. 1998; 791 186-190
- 185 Tominaga A, Sugawara H, Inoue K. et al . Implication of pituitary adenylate cyclase-activating polypeptide (PACAP) for neuroprotection of nicotinic acetylcholine receptor signalling in PC12 cells. J Mol Neurosci. 2008; 36 73-78
- 186 Trauth JA, Seidler FJ, Slotkin TA. An animal model of adolescent nicotine exposure: effects on gene expression and macromolecular constituents in rat brain regions. Brain Res. 2000; 867 29-39
- 187 Uchida S, Kagitani F, Nakayama H. et al . Effect of stimulation of nicotinic cholinergic receptors on cortical cerebral blood flow and changes in the effects during aging in anesthetized rats. Neurosci Lett. 1997; 228 203-206
- 188 Ulrich J, Johannson-Locher G, Seiler WO. et al . Does smoking protect from Alzheimer's disease? Alzheimer-type changes in 301 unselected brains from patients with known smoking history. Acta Neuropathol. 1997; 94 450-454
- 189 Utsugisawa K, Nagane Y, Tohgi H. et al . Changes with aging and ischemia in nicotinic acetylcholine receptor subunit alpha7 mRNA expression in postmortem human frontal cortex and putamen. Neurosci Lett. 1999; 270 145-148
- 190 Utsuki T, Shoaib M, Holloway HW. et al . Nicotine lowers the secretion of the Alzheimer's amyloid beta-protein precursor that contains amyloid beta-peptide in rat. J Alzheimers Dis. 2002; 4 405-415
- 191 Vernino S, Amador M, Luetje CW. et al . Calcium modulation and high calcium permeability of neuronal nicotinic acetylcholine receptors. Neuron. 1992; 8 127-134
- 192 Wang BW, Liao WN, Chang CT. et al . Facilitaion of glutamate release by nicotine involves the activation of a Ca2+/calmodulin signalling pathway in rat prefrontal cortex nerve terminals. Synapse. 2006; 59 491-501
- 193 Wang HL, Chen XT, Luo L. et al . Reparatory effects of nicotine on NMDA receptor-mediated synaptic plasticity in the hippocampal CA1 region of chronically lead-exposed rats. Eur J Neurosci. 2006; 23 1111-1119
- 194 Wang HY, Lee DH, D’Andrea MR. et al . beta-Amyloid (1–42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease. J Biol Chem. 2000; 275 5626-5632
- 195 Wang L, Kittaka M, Sun N. et al . Chronic nicotine treatment enhances focal ischemic brain injury and depletes free pool of brain microvascular tissue plasminogen activator in rats. J Cer Blood Flow Metabol. 1997; 17 136-146
- 196 Warpman U, Nordberg A. Epibatidine and ABT 418 reveal selective losses of alpha 4 beta 2 nicotinic receptors in Alzheimer brains. NeuroReport. 1995; 6 2419-2423
- 197 Wessels C, Winterer G. Effects of nicotine on neurodevelopment (article in German). Nervenarzt. 2008; 79 7-8 10-12 14-16
- 198 Yildiz D, Ercal N, Armstrong DW. Nicotine enantiomers and oxidative stress. Toxicology. 1998; 130 155-165
- 199 Yildiz D, Liu Ys, Ercal N. et al . Comparison of pure nicotine- and smokeless tobacco extract-induced toxicities and oxidative stress. Arch Environ Contam Toxicol. 1999; 37 434-439
- 200 Zamani MR, Allen YS. Nicotine and its interaction with beta-amyloid protein: a short review. Biol Psychiatry. 2001; 49 221-232
- 201 Zamani MR, Allen YS, Owen GP. et al . Nicotine modulates the neurotoxic effect of beta-amyloid protein (25–35) in hippocampal cultures. NeuroReport. 1997; 8 513-517
- 202 Zanardi A, Leo G, Biagini G. et al . Nicotine and neurodegeneration in ageing. Toxicol Lett. 2002; 127 207-215
- 203 Zhang J, Liu Q, Chen Q. et al . Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal homeostasis. FASEB J. 2006; 20 1212-1214
- 204 Zhang X, Wahlstrom G, Nordberg A. Influence of development and aging on nicotinic receptor subtypes in rodent brain. Int J Dev Neurosci. 1990; 8 715-721
- 205 Zhao B. Natural antioxidants protect neurons in Alzheimer's disease and Parkinson's disease. Neurochem Res. 2009; Ahead of print
- 206 Zilles K, Becker CM, Schleicher A. Nicotinic ACh receptor blockade and spontaneous nerve cell death in various brain regions. Bibliotheca Anatomica. 1982; 23 40-55
- 207 Zoli M, Léna C, Picciotto MR. et al . Identification of four classes of brain nicotinic receptors using β2-mutant mice. J Neurosci. 1998; 18 4461-4472
- 208 Zoli M, Picciotto MR, Ferrari R. et al . Increased neurodegeneration during aging in mice lacking high-affinity nicotine receptors. EMBO J. 1999; 18 1235-1244
Correspondence
Dr. S. Ferrea
Rheinische Kliniken Düsseldorf
Klinik und Poliklinik für Psychiatrie und Psychotherapie
Heinrich-Heine-Universität Düsseldorf
Bergische Landstraße 2
40629 Düsseldorf
Germany
Phone: +49 211 922-0
Fax: +49 211 922-3498
Email: Stefano.Ferrea@lvr.de