The DOI matches its Crossref record; 60 of the 62 references it cites were found in a registry or an index.
Molecular analysis of nicotinic receptor expression in autism
Open accessAbstract
Autism is a developmental disorder of unknown aetiopathology and lacking any specific pharmacological therapeutic intervention. Neurotransmitters such as serotonin, gamma-aminobutyric acid (GABA) and acetylcholine have been implicated. Abnormalities in nicotinic acetylcholine receptors have been identified including cortical loss of binding to the alpha4/beta2 subtype and increase in cerebellar alpha7 binding. Receptor expression (mRNA) has not so far been systematically examined. This study aims to further explore the role of nicotinic receptors in autism by analysing nicotinic receptor subunit mRNA in conjunction with protein levels and receptor binding in different brain areas. Quantitative RT-PCR for alpha4, alpha7 and beta2 subunit mRNA expression levels; alpha3, alpha4, alpha7 and beta2 subunit protein expression immunochemistry and specific radioligand receptor binding were performed in adult autism and control brain samples from cerebral cortex and cerebellum. Alpha4 and beta2 protein expression and receptor binding density as well as alpha4 mRNA levels were lower in parietal cortex in autism, while alpha7 did not change for any of these parameters. In cerebellum, alpha4 mRNA expression was increased, whereas subunit protein and receptor levels were decreased. Alpha7 receptor binding in cerebellum was increased alongside non-significant elevations in mRNA and protein expression levels. No significant changes were found for beta2 in cerebellum. The data obtained, using complementary measures of receptor expression, indicate that reduced gene expression of the alpha4beta2 nicotinic receptor in the cerebral cortex is a major feature of the neurochemical pathology of autism, whilst post-transcriptional abnormalities of both this and the alpha7 subtype are apparent in the cerebellum. The findings point to dendritic and/or synaptic nicotinic receptor abnormalities that may relate to disruptions in cerebral circuitry development.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“A follow up study [173] found increased α4 mRNA expression in cerebellum but subunit protein levels and binding decreased.”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [173]
Citations
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 316,394
Unusual brain growth patterns in early life in patients with autistic disorder: An MRI study
Courchesne, E., Karns, C. M., Davis, H. R., Ziccardi, R., Carper, R. A., Tigue, Z. D., Chisum, H. J., Moses, P., Pierce, K., Lord, C., et al. (2001) · Neurology · doi:10.1212/wnl.57.2.245 · Cited by 1,487
A clinicopathological study of autism
Bailey, A. (1998) · Brain · doi:10.1093/brain/121.5.889 · Cited by 1,083
Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors
McGehee, D. S., Heath, M. J. S., Gelber, S., Devay, P., & Role, L. W. (1995) · Science · doi:10.1126/science.7569895 · Cited by 1,070
A Twin Study of Autism in Denmark, Finland, Iceland, Norway and Sweden
Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I. C., Jakobsson, G., & Bohman, M. (1989) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1989.tb00254.x · Cited by 780
First genetic evidence of GABAA receptor dysfunction in epilepsy: a mutation in the γ2-subunit gene
Baulac, S., Huberfeld, G., Gourfinkel‐An, I., Mitropoulou, G., Beranger, A., Prud’homme, J.-F., Baulac, M., Brice, A., Bruzzone, R., & Leguern, É. (2001) · Nature Genetics · doi:10.1038/ng0501-46 · Cited by 765
(1986) · American Journal of Psychiatry · doi:10.1176/ajp.143.7.862 · Cited by 590
Postmortem brain abnormalities of the glutamate neurotransmitter system in autism
Purcell, A. E., Jeon, O. H., Zimmerman, A. W., Blue, M. E., & Pevsner, J. (2001) · Neurology · doi:10.1212/wnl.57.9.1618 · Cited by 518
Serotonin and brain development: role in human developmental diseases
Whitaker-Azmitia, P. M. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00615-3 · Cited by 506
Fatemi, S. H., Halt, A. R., Stary, J. M., Kanodia, R., Schulz, S. C., & Realmuto, G. R. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01430-0 · Cited by 500
AUTISM IN THALIDOMIDE EMBRYOPATHY: A POPULATION STUDY
Strömland, K., Nordin, V., Miller, M. T., Åkerström, B., & Gillberg, C. (1994) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.1994.tb11856.x · Cited by 453
Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation
Nelson, K. B., Grether, J. K., Croen, L., Dambrosia, J. M., Dickens, B. F., Jelliffe‐Pawlowski, L. L., Hansen, R. L., & Phillips, T. M. (2001) · Annals of Neurology · doi:10.1002/ana.1024 · Cited by 434
Fetal valproate syndrome and autism: additional evidence of an association
Williams, G., King, J. O., Cunningham, M. L., Stephan, M., Kerr, B. A., & Hersh, J. H. (2001) · Developmental Medicine & Child Neurology · doi:10.1017/s001216220100038x · Cited by 431
Identification of Four Classes of Brain Nicotinic Receptors Using β2 Mutant Mice
Zoli, M., Léna, C., Picciotto, M. R., & Changeux, J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-12-04461.1998 · Cited by 404
Altered serotonin synthesis in the dentatothalamocortical pathway in autistic boys
Chugani, D. C., Muzik, O., Rothermel, R., Behen, M. E., Chakraborty, P. K., Mangner, T. J., Silva, E. A. D., & Chugani, H. T. (1997) · Annals of Neurology · doi:10.1002/ana.410420420 · Cited by 399
Cholinergic Activity in Autism: Abnormalities in the Cerebral Cortex and Basal Forebrain
Perry, E. K., Lee, M., Martin-Ruiz, C. M., COURT, J. A., Volsen, S. G., Merrit, J., Folly, E. A., Iversen, P. E., Bauman, M. L., Perry, R. H., et al. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.7.1058 · Cited by 390
Self-citationIdentification of four classes of brain nicotinic receptors using beta2 mutant mice.
Zoli, M., Léna, C., Picciotto, M. R., & Changeux, J. (1998) · PubMed Central · doi:10.1523/jneurosci.18-12-04461.1996 · Cited by 387
Blatt, G. J., Fitzgerald, C. M., Guptill, J. T., Booker, A. B., Kemper, T. L., & Bauman, M. L. (2001) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1013238809666 · Cited by 322
Antidepressant-Induced Sexual Dysfunction
Gregorian, R. S., Golden, K. A., Bahce, A., Goodman, C., Kwong, W. J., & Khan, Z. M. (2002) · Annals of Pharmacotherapy · doi:10.1345/aph.1a195 · Cited by 320
Linkage and association of the glutamate receptor 6 gene with autism
Jamain, S., Betancur, C., Quach, H., Philippe, A., Fellous, M., Giros, B., Gillberg, C., Leboyer, M., & Bourgeron, T. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4000979 · Cited by 318
Neurotransmitters and neuromodulators during early human development
Herlenius, E., & Lagercrantz, H. (2001) · Early Human Development · doi:10.1016/s0378-3782(01)00189-x · Cited by 290
Linking etiologies in humans and animal models: Studies of autism
Rodier, P. M., Ingram, J. L., Tisdale, B., & Croog, V. J. (1997) · Reproductive Toxicology · doi:10.1016/s0890-6238(97)80001-u · Cited by 248
Nicotinic receptor abnormalities in the cerebellar cortex in autism
Lee, M. (2002) · Brain · doi:10.1093/brain/awf160 · Cited by 232
Self-citationNeurofunctional mechanisms in autism
Waterhouse, L., Fein, D., & Modahl, C. (1996) · Psychological Review · doi:10.1037/0033-295x.103.3.457 · Cited by 218
Bauman, M. L. (2006) · Johns Hopkins University Press eBooks · doi:10.1353/book.3225 · Cited by 215
Parietal lobe abnormalities detected with MR in patients with infantile autism.
Courchesne, E., Press, G. A., & Yeung-Courchesne, R. (1993) · American Journal of Roentgenology · doi:10.2214/ajr.160.2.8424359 · Cited by 214
Role of the serotonin transporter gene in the behavioral expression of autism
Tordjman, S., Gutknecht, L., Carlier, M., Spitz, E., Antoine, C., Slama, F., Carsalade, V, Cohen, D. J., Ferrari, P., Roubertoux, P. L., et al. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000873 · Cited by 196
Martin-Ruiz, C. M., COURT, J. A., Molnár, E., Lee, M., Gotti, C., Mamalaki, A., Tsouloufis, T., Tzartos, S. J., Ballard, C. G., Perry, R. H., et al. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0731635.x · Cited by 194
Self-citationBurghaus, L., Schütz, U., Krempel, U., de Vos, R. A. I., Steur, E. N. H. J., Wevers, A., Lindstrom, J. M., & Schröder, H. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00031-0 · Cited by 178
Remington, G. J., Sloman, L., Konstantareas, M. M., Parker, K., & Gow, R. M. (2001) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200108000-00012 · Cited by 164
Neuronal Nicotinic Receptor Subtypes
Lindstrom, J. M., Anand, R., Peng, X.-D., Gerzanich, V., Wang, F., & LI, Y. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb17467.x · Cited by 160
Posey, D. J., Guenin, K. D., Kohn, A. E., Swiezy, N. B., & McDougle, C. J. (2001) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/10445460152595586 · Cited by 157
Flores, C. M., Dávila‐García, M. I., Ulrich‐Lai, Y. M., & Kellar, K. J. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69052216.x · Cited by 142
Whiting, P. J., Liu, R., Morley, B., & Lindstrom, J. M. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-12-04005.1987 · Cited by 138
Malone, R. P., Maislin, G., Choudhury, M. S., Gifford, C., & Delaney, M. A. (2002) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200202000-00007 · Cited by 127
Ahlsén, G., Rosengren, L., Belfrage, M., Palm, A., Haglid, K. G., Hamberger, A., & Gillberg, C. (1993) · Biological Psychiatry · doi:10.1016/0006-3223(93)90124-v · Cited by 120
Neuronal nicotinic receptors, important new players in brain function
Clementi, F., Fornasari, D., & Gotti, C. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00066-2 · Cited by 110
Whiting, P. J., Schoepfer, R., Swanson, L. W., Simmons, D. M., & Lindstrom, J. M. (1987) · Nature · doi:10.1038/327515a0 · Cited by 91
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
Self-citationAntiepileptic drugs: affective use in autism spectrum disorders
Martino, A. D., & Tuchman, R. F. (2001) · Pediatric Neurology · doi:10.1016/s0887-8994(01)00276-4 · Cited by 85
Fatemi, S. H., & Halt, A. R. (2001) · Synapse · doi:10.1002/syn.10002 · Cited by 79
Croonenberghs, J. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00131-1 · Cited by 77
Stability of RNA transcripts in post-mortem psychiatric brains
Schramm, M., Falkai, P., Tepest, R., et al. (1999) · Journal of Neural Transmission · doi:10.1007/s007020050162 · Cited by 68
Nicotinic receptors in dementia of Alzheimer, Lewy body and vascular types
Martin-Ruiz, C. M., COURT, J. A., Lee, M., Piggott, M. A., Johnson, M. A., Ballard, C. G., Kalaria, R. N., Perry, R., & Perry, E. K. (2000) · Acta Neurologica Scandinavica · doi:10.1034/j.1600-0404.2000.00305.x · Cited by 61
Self-citationCATECHOLAMINERGIC METABOLISM AND AUTISM
Martineau, J., Hérault, J., Petit, E., Guérin, P., Hameury, L., Perrot, A., Mallet, J., Sauvage, D., Lelord, G., & Müh, J. (1994) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.1994.tb11911.x · Cited by 57
Ghosh, S. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19970407)380:2 · Cited by 53
Didier, M., Berman, S. A., Lindstrom, J. M., & Bursztajn, S. (1995) · Molecular Brain Research · doi:10.1016/0169-328x(94)00266-h · Cited by 50
Src, ras, and rac mediate the migratory response elicited by NGF and PMA in PC12 cells
Altun-Gultekin, Z. F., & Wagner, J. A. (1996) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19960515)44:4 · Cited by 49
Buitelaar, J. K., & Willemsen‐Swinkels, S. H. N. (2000) · Pediatric Drugs · doi:10.2165/00148581-200002010-00006 · Cited by 46
Martin-Ruiz, C. M., Piggott, M. A., Gotti, C., Lindstrom, J. M., Mendelow, A. D., Siddique, M. S., Perry, R. H., Perry, E. K., & COURT, J. A. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(00)00110-6 · Cited by 43
Self-citationMutation screening of human 5-HT2Breceptor gene in early-onset obsessive-compulsive disorder
Kim, S.-J., Veenstra-VanderWeele, J. M., Hanna, G. L., Gonen, D., LEVENTHAL, B. L., & Cook, E. (2000) · Molecular and Cellular Probes · doi:10.1006/mcpr.1999.0281 · Cited by 33
Gangliosides in children with autism
Lekman, A. Y., Skjeldal, O. H., Sponheim, E., et al. (1995) · Acta Paediatrica · doi:10.1111/j.1651-2227.1995.tb13757.x · Cited by 24
Analysis of ten candidate genes in autism by association and linkage
Philippe, A., GUILLOUD-BATAILLE, M., Martinez, M. M., Gillberg, C., Råstam, M., Sponheim, E., Coleman, M., Zappella, M., Aschauer, H. N., Penet, C., et al. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10041 · Cited by 23
Souery, D., Lipp, O., Rivelli, S. K., Massat, I., Serretti, A., Cavallini, M. C., Ackenheil, M., Adolfsson, R., Aschauer, H. N., Blackwood, D., et al. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19991015)88:5 · Cited by 19
Zubenko, G. S., Stiffler, J. S., Hughes, H. B., Hurtt, M. R., & Kaplan, B. B. (1998) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19980328)81:2 · Cited by 18
Wolf, P., Hösli, E., Roches, J. C., et al. (2008) · European Neurology · doi:10.1159/000114660 · Cited by 18
Targeting α7-containing nicotinic receptors on neurons to distal locations
Roth, A. L., Shoop, R. D., & Berg, D. K. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00092-3 · Cited by 14
Autism and cerebellum. An unusual finding with MRI.
Muratori, F., Cesari, A., & Casella, C. (2001) · PubMed · Cited by 4
Maestrini, E., Lai, C., Marlow, A., et al. (1999) · Research Explorer (The University of Manchester) · doi:10.25405/ncl.34583109 · Cited by 3
Rodier (1996) · doi:10.1002/(sici)1096-9861(19960624)370:2
Flagged first, then by citations
2 of the 62 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Buitelaar, 2000, Autism: current theories regarding its pathogenesis and implications for rational pharmacotherapy, Paediatr. Drugs, 2, 67, 10.2165/00128072-200002010-00006 · DOI
- McQueen, 2002, Secretin for the treatment of autism, Ann. Pharmacother., 36, 305, 10.1345/aph.19113 · DOI · Paper page
Cited by
Sorted by citations
Brain nicotinic acetylcholine receptors: native subtypes and their relevance
Gotti, C., Zoli, M., & Clementi, F. (2006) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.07.004 · Cited by 882
Neuronal nicotinic receptors: from structure to pathology
Gotti, C., & Clementi, F. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.09.006 · Cited by 970
Consensus Paper: Pathological Role of the Cerebellum in Autism
Fatemi, S. H., Aldinger, K. A., Ashwood, P., Bauman, M. L., Blaha, C. D., Blatt, G. J., Chauhan, A., Chauhan, V., Dager, S. R., Dickson, P. E., et al. (2012) · The Cerebellum · doi:10.1007/s12311-012-0355-9 · Cited by 723
Brain growth across the life span in autism: Age-specific changes in anatomical pathology
Courchesne, E., Campbell, K., & Solso, S. (2011) · Brain Research · doi:10.1016/j.brainres.2010.09.101 · Cited by 711
Nicotinic ACh receptors as therapeutic targets in CNS disorders
Dineley, K. T., Pandya, A. A., & Yakel, J. L. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.12.002 · Cited by 460
Metadata
- Authors
- Martin-Ruiz, C. M., Lee, M., Perry, R. H., Baumann, M., Court, J. A., & Perry, E. K.
- Affiliations
- Newcastle upon Tyne Hospital (GB)
- Harvard University (US)
- Corresponding author
- Martin-Ruiz, C.M.
- ORCID
- Martin-Ruiz, C.M.
- Venue
- Molecular Brain Research
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 123
- Issue
- 1-2
- Pages
- 81-90
- ISSN
- 0169-328X (ISSN-L)
- OpenAlex
- W2146597551
- Cited by
- 141
- References
- 62
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 9 · 2020: 5 · 2019: 1 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 13 · 2014: 4 · 2013: 12 · 2012: 5
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Molecular Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- autism spectrum disorder, nicotinic acetylcholine receptors, alpha4beta2 nicotinic receptor, alpha7 nicotinic acetylcholine receptor, cerebral cortex, cerebellum, receptor binding density, post-transcriptional regulation
- MeSH terms
- Acetylcholine, Adult, Autistic Disorder, Binding, Competitive, Brain, Brain Chemistry, Cerebellum, Female, Humans, Immunohistochemistry, Male, Synaptic Transmission, Parietal Lobe, Radioligand Assay, Receptors, Nicotinic, RNA, Messenger, Synapses, Down-Regulation, Up-Regulation, Protein Subunits, alpha7 Nicotinic Acetylcholine Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
