Nicotinic receptors in human brain: topography and pathology

Court, Jenny A.; Martin-Ruiz, Carmen; Graham, Alison; Perry, Elaine

doi:10.1016/s0891-0618(00)00110-1

Cited by 180Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchSmoking Behavior and Cessation

Nicotinic receptors in human brain: topography and pathology

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Court, Jenny A., Martin-Ruiz, Carmen, Graham, Alison, Perry, Elaine·2000·Journal of Chemical Neuroanatomy

DOI 10.1016/s0891-0618(00)00110-1

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Abstract

Brain nicotinic acetylcholine receptors (nAChR) are a class of ligand-gated channels composed of alpha and beta subunits with specific structural, functional and pharmacological properties. They participate in the physiological and behavioural effects of acetylcholine and mediate responses to nicotine. They are associated with numerous transmitter systems and their expression is altered during development and ageing as well as in diseases such as autism, schizophrenia, Alzheimer's disease, Parkinson's disease and Lewy body dementia. Nicotinic receptors containing a number of different subunits are highly expressed during early human development. Disorders believed to be associated with abnormal brain maturation involve deficits in both alpha4beta2, in the case of autism, and alpha7 possibly in addition to alpha4beta2 nAChRs in the case of schizophrenia. In ageing and age-related neurodegenerative disorders nAChR deficits are predominantly associated with alpha4-containing receptors, although some studies also indicate the involvement of alpha3 and alpha7 subunits. Whilst ageing appears to be associated with reductions in subunit mRNA as well as protein expression, in Alzheimer's disease only protein loss is apparent. Nicotinic therapy may be of benefit in a number of neurological conditions, however studies evaluating further both the distribution of specific subunit involvement and the correlation of nAChR deficits with clinical symptoms are required to inform therapeutic strategy.

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The heteromeric a4b2* subtype and the homomeric a7 are the most prevalent receptor subtypes in the central nervous system.
“The heteromeric a4b2* subtype and the homomeric a7 are the most prevalent receptor subtypes in the central nervous system (Court et al., 2000).”
From Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors (2014) · cites this paper as Court et al., 2000

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Chronic nicotine treatment prevents neuronal loss in neocortex resulting from nucleus basalis lesions in young adult and aged rats
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Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization
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Alzheimer’s disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies
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Cellular and synaptic mechanisms of nicotine addiction
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Smoking, nicotine and Parkinson's disease
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Nicotinic Acetylcholine Receptor Distribution in Alzheimer's Disease, Dementia with Lewy Bodies, Parkinson's Disease, and Vascular Dementia: In Vitro Binding Study Using 5-[125I]-A-85380
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A critical review of neonicotinoid insecticides for developmental neurotoxicity
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Nicotinic–serotonergic interactions in brain and behaviour
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Therapeutic Potential of α7 Nicotinic Acetylcholine Receptors
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Acetylcholinesterase and Butyrylcholinesterase – Important Enzymes of Human Body
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Striatal α6* Nicotinic Acetylcholine Receptors: Potential Targets for Parkinson’s Disease Therapy
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Selective nicotinic acetylcholine receptor subunit deficits identified in Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies by immunoprecipitation
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Function of Partially Duplicated Human α7 Nicotinic Receptor Subunit CHRFAM7A Gene
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Alzheimer's disease and anaesthesia: implications for the central cholinergic system
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Nicotinic receptors as CNS targets for Parkinson's disease
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Alpha7 Nicotinic Acetylcholine Receptors Modulate Motivation to Self-Administer Nicotine: Implications for Smoking and Schizophrenia
Brunzell, D. H., & McIntosh, J. M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.299 · Cited by 114 · see citing works
2 [ 18 F]F‐A85380: PET imaging of brain nicotinic acetylcholine receptors and whole body distribution in humans
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Cholinergic nicotinic receptors: Competitive ligands, allosteric modulators, and their potential applications
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Stimulating Nicotinic Receptors Trigger Multiple Pathways Attenuating Cytotoxicity in Models of Alzheimer's and Parkinson's Diseases
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Nicotinic actions on neuronal networks for cognition: General principles and long-term consequences
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Alpha7 nicotinic acetylcholine receptor: A link between inflammation and neurodegeneration
Conejero‐Goldberg, C., Davies, P., & Ulloa, L. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.10.007 · Cited by 100 · see citing works
Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors
Kassam, S. M., Herman, P. M., Goodfellow, N. M., Alves, N. C., & Lambe, E. K. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2645-08.2008 · Cited by 100 · see citing works
Localization of [3H]nicotine, [3H]cytisine, [3H]epibatidine, and [125I]α‐bungarotoxin binding sites in the brain of Macaca mulatta
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Nicotinic Receptor-Mediated Neuroprotection in Neurodegenerative Disease Models
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In vivo Brain Imaging of Human Exposure to Nicotine and Tobacco
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6‐[18F]Fluoro‐A‐85380, a new PET tracer for the nicotinic acetylcholine receptor: Studies in the human brain and in vivo demonstration of specific binding in white matter
Ding, Y., Fowler, J. S., Logan, J., Wang, G., Telang, F., Garza, V., Biegon, A. R., Pareto, D., Rooney, W. D., Shea, C. E., et al. (2004) · Synapse · doi:10.1002/syn.20051 · Cited by 89 · see citing works
Scientific Opinion on the developmental neurotoxicity potential of acetamiprid and imidacloprid
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Nicotinic Cholinergic Receptors in the Rat Cerebellum: Multiple Heteromeric Subtypes
Turner, J. R., & Kellar, K. J. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2112-05.2005 · Cited by 89 · see citing works
The role of astrocytic α7 nicotinic acetylcholine receptors in Alzheimer disease
Fontana, I. C., Kumar, A., & Nordberg, A. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00792-4 · Cited by 86 · see citing works
Subunit Composition of Nicotinic Receptors in Monkey Striatum: Effect of Treatments with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine or l-DOPA
Quik, M., Vailati, S., Bordia, T., Kulak, J. M., Fan, H., McIntosh, J. M., Clementi, F., & Gotti, C. (2004) · Molecular Pharmacology · doi:10.1124/mol.104.006015 · Cited by 86 · see citing works
Immunohistochemical localisation of nicotinic acetylcholine receptor subunits in human cerebellum
Graham, A., COURT, J. A., Martin-Ruiz, C. M., Jaros, E., Perry, R., Volsen, S. G., Bose, S., Evans, N. M., Ince, P. G., Kuryatov, A., et al. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00223-3 · Cited by 85 · see citing works
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Differential nicotinic acetylcholine receptor subunit expression in the human hippocampus
Graham, A. J., Ray, M. A., Perry, E. K., Jaros, E., Perry, R. H., Volsen, S. G., Bose, S., Evans, N. M., Lindstrom, J. M., & COURT, J. A. (2003) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(02)00100-x · Cited by 85 · see citing works
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Differential Declines in Striatal Nicotinic Receptor Subtype Function after Nigrostriatal Damage in Mice
Quik, M., Sum, J., Whiteaker, P., McCallum, S. E., Marks, M. J., Musachio, J. L., McIntosh, J. M., Collins, A. C., & Grady, S. R. (2003) · Molecular Pharmacology · doi:10.1124/mol.63.5.1169 · Cited by 83 · see citing works
Smoking during early pregnancy affects the expression pattern of both nicotinic and muscarinic acetylcholine receptors in human first trimester brainstem and cerebellum
Falk, L. L., Nordberg, A. K., Seiger, Å., Kjældgaard, A., & Hellström‐Lindahl, E. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.12.049 · Cited by 82 · see citing works
The potential use of rabies virus glycoprotein-derived peptides to facilitate drug delivery into the central nervous system: a mini review
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Cyto- and receptor architectonic mapping of the human brain
Palomero‐Gallagher, N., & Zilles, K. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63639-3.00024-4 · Cited by 74 · see citing works
Human Brain Imaging of α7 nAChR with [18F]ASEM: a New PET Radiotracer for Neuropsychiatry and Determination of Drug Occupancy
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4 2 nicotinic receptor status in Alzheimer's disease using 123I-5IA-85380 single-photon-emission computed tomography
O'Brien, J. T., Colloby, S. J., Pakrasi, S., Perry, E. K., Pimlott, S. L., Wyper, D., McKeith, I. G., & Williams, E. D. (2006) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2006.108209 · Cited by 73 · see citing works
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Lifetime cigarette smoking is associated with striatal volume measures
Das, D., Cherbuin, N., Anstey, K. J., Sachdev, P. S., & Easteal, S. (2011) · Addiction Biology · doi:10.1111/j.1369-1600.2010.00301.x · Cited by 72 · see citing works
Alpha7 neuronal nicotinic receptors as a drug target in schizophrenia
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Inattentiveness, parental smoking and adolescent smoking initiation
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Loss of α‐conotoxinMII‐ and A85380‐sensitive nicotinic receptors in Parkinson's disease striatum
Quik, M., Bordia, T., Forno, L. S., & McIntosh, J. M. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02177.x · Cited by 62 · see citing works
The potential role of cotinine in the cognitive and neuroprotective actions of nicotine
Buccafusco, J. J., & Terry, A. V. (2003) · Life Sciences · doi:10.1016/s0024-3205(03)00226-1 · Cited by 62 · see citing works
Nicotinic receptor subtypes in human brain related to aging and dementia
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PET Imaging of Cholinergic Neurotransmission in Neurodegenerative Disorders
Tiepolt, S., Meyer, P., Patt, M., Deuther‐Conrad, W., Hesse, S., Barthel, H., & Sabri, O. (2022) · Journal of Nuclear Medicine · doi:10.2967/jnumed.121.263198 · Cited by 61 · see citing works
An increase in intracellular free calcium ions by nicotinic acetylcholine receptors in a single cultured rat cortical astrocyte
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Impaired Off-Line Consolidation of Motor Memories After Combined Blockade of Cholinergic Receptors During REM Sleep-Rich Sleep
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Nicotinic acetylcholine receptor immunohistochemistry in Alzheimer's disease and dementia with Lewy bodies: differential neuronal and astroglial pathology
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The role of cortical cholinergic pre- and post-synaptic receptors in taste memory formation
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Relevance of Donepezil in Enhancing Learning and Memory in Special Populations: A Review of the Literature
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5‐Iodo‐A‐85380 binds to α‐conotoxin MII‐sensitive nicotinic acetylcholine receptors (nAChRs) as well as α4β2* subtypes
Kulak, J. M., Sum, J., Musachio, J. L., McIntosh, J. M., & Quik, M. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00868.x · Cited by 53 · see citing works
Oxidative Stress Induced Mitochondrial DNA Deletion as a Hallmark forthe Drug Development in the Context of the Cerebrovascular Diseases
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In SilicoModels for the Human α4β2 Nicotinic Acetylcholine Receptor
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Alzheimer’s Disease and Genetics of Inflammation: A Pharmacogenomic Vision
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Brain volumes and neuropsychological performance are related to current smoking and alcoholism history
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Declines in Different β2* Nicotinic Receptor Populations in Monkey Striatum after Nigrostriatal Damage
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Higher expression of α7 nicotinic acetylcholine receptors in human fetal compared to adult brain
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Acetylcholinesterase inhibitors may improve myelin integrity
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Diverse strategies targeting α7 homomeric and α6β2* heteromeric nicotinic acetylcholine receptors for smoking cessation
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Synthesis and biodistribution of radiolabeled alpha 7 nicotinic acetylcholine receptor ligands.
Pomper, M. G., Phillips, E. D., Fan, H. S., McCarthy, D. J., Keith, R. A., Gordon, J. C., Scheffel, U., Dannals, R. F., & Musachio, J. L. (2005) · PubMed · Cited by 41 · see citing works
Nitrous Oxide and Xenon Inhibit the Human (α7)5 Nicotinic Acetylcholine Receptor Expressed in Xenopus Oocyte
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LC3 overexpression reduces Aβ neurotoxicity through increasing α7nAchR expression and autophagic activity in neurons and mice.
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Simplified quantification of nicotinic receptors with 2[18F]F-A-85380 PET
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Microarray Technology and its Application on Nicotine Research
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Are neuronal nicotinic receptors a target for antiepileptic drug development? Studies in different seizure models in mice and rats
Löscher, W., Potschka, H., Właź, P., Danysz, W., & Parsons, C. G. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01542-5 · Cited by 38 · see citing works
Development of [ 18 F]ASEM, a specific radiotracer for quantification of the α7-nAChR with positron-emission tomography
Horti, A. G. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.07.030 · Cited by 37 · see citing works
Molecular imaging of neuropsychiatric symptoms in Alzheimer's and Parkinson's disease
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The distribution of the alpha7 nicotinic acetylcholine receptor in healthy aging: An in vivo positron emission tomography study with [18F]ASEM
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Assessment of α7 nicotinic acetylcholine receptor availability in juvenile pig brain with [18F]NS10743
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Authors: Court, J. A., Martin-Ruiz, C., Graham, A., & Perry, E.
Affiliations: Newcastle University (GB)
Corresponding author: Court, Jenny A.
ORCID: Martin-Ruiz, Carmen
Venue: Journal of Chemical Neuroanatomy
Publisher: Elsevier BV
Published: 2000-12
Volume: 20
Issue: 3-4
Pages: 281-298
ISSN: 0891-0618 (ISSN-L)
DOI: 10.1016/s0891-0618(00)00110-1
OpenAlex: W1967131207
Cited by: 180
References: 186
Citations by year: 2026: 1 · 2025: 2 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 9 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 6 · 2012: 8
FWCI: 0.69
Type: journal article
Language: en
Open access: green
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Chemical Neuroanatomy (publishedVersion)
PubMed (publishedVersion)
Newcastle University ePrints (Newcastle Univesity)
Funders: Eli Lilly and Company
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
Keywords: nicotinic acetylcholine receptors, human brain, receptor subunit expression, alpha4beta2 nAChR, alpha7 nAChR, brain development, brain aging, neurodegeneration, autism spectrum disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies
MeSH terms: Brain Chemistry, Brain Diseases, Humans, Receptors, Nicotinic

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Nicotinic receptors in human brain: topography and pathology

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