{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T14:33:35Z","timestamp":1774017215524,"version":"3.50.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurosci"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>It has been estimated that more than 50% of patients with Neurofibromatosis type 1 (NF1) have neurobehavioral impairments which include attention deficit\/hyperactivity disorder, visual\/spatial learning disabilities, and a myriad of other cognitive developmental problems. The biological mechanisms by which <jats:italic>NF1<\/jats:italic> gene mutations lead to such cognitive deficits are not well understood, although excessive Ras signaling and increased GABA mediated inhibition have been implicated. It is proposed that the cognitive deficits in NF1 are the result of dysfunctional cellular trafficking and localization of molecules downstream of the primary gene defect.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>To elucidate genes involved in the pathogenic process, gene expression analysis was performed comparing the expression profiles in various brain regions for control and <jats:italic>Nf1<\/jats:italic>\n              <jats:sup>+\/-<\/jats:sup> heterozygous mice. Gene expression analysis was performed for hippocampal samples dissected from postnatal day 10, 15, and 20 mice utilizing the Affymetrix Mouse Genome chip (Murine 430 2.0). Analysis of expression profiles between <jats:italic>Nf1<\/jats:italic>\n              <jats:sup>+\/-<\/jats:sup>and wild-type animals was focused on the hippocampus because of previous studies demonstrating alterations in hippocampal LTP in the <jats:italic>Nf1<\/jats:italic>\n              <jats:sup>+\/-<\/jats:sup> mice, and the region's importance in visual\/spatial learning. Network analysis identified links between neurofibromin and kinesin genes, which were down regulated in the <jats:italic>Nf1<\/jats:italic>\n              <jats:sup>+\/-<\/jats:sup> mice at postnatal days 15 and 20.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Through this analysis, it is proposed that neurofibromin forms a binding complex with amyloid precursor protein (APP) and through filamin proteins interacts with a dopamine receptor (Drd3). Though the effects of these interactions are not yet known, this information may provide novel ideas about the pathogenesis of cognitive defects in NF1 and may facilitate the development of novel targeted therapeutic interventions.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2202-7-22","type":"journal-article","created":{"date-parts":[[2006,3,10]],"date-time":"2006-03-10T19:19:59Z","timestamp":1142018399000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cognitive dysfunction in NFI knock-out mice may result from altered vesicular trafficking of APP\/DRD3 complex"],"prefix":"10.1186","volume":"7","author":[{"given":"Elizabeth A","family":"Donarum","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca F","family":"Halperin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietrich A","family":"Stephan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinodh","family":"Narayanan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2006,3,8]]},"reference":[{"key":"227_CR1","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1093\/hmg\/9.7.1059","volume":"9","author":"JL Rutkowski","year":"2000","unstructured":"Rutkowski JL, Wu K, Gutmann DH, Boyer PJ, Legius E: Genetic and cellular defects contributing to benign tumor formation in neurofibromatosis type 1. Hum Mol Genet. 2000, 9: 1059-1066. 10.1093\/hmg\/9.7.1059.","journal-title":"Hum Mol Genet"},{"key":"227_CR2","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1002\/1096-8628(200022)97:2<119::AID-AJMG3>3.0.CO;2-3","volume":"97","author":"K North","year":"2000","unstructured":"North K: Neurofibromatosis type 1. Am J Med Genet. 2000, 97: 119-27. 10.1002\/1096-8628(200022)97:2<119::AID-AJMG3>3.0.CO;2-3.","journal-title":"Am J Med Genet"},{"key":"227_CR3","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1002\/(SICI)1096-8628(19990326)89:1<45::AID-AJMG9>3.0.CO;2-J","volume":"89","author":"S Ozonoff","year":"1999","unstructured":"Ozonoff S: Cognitive impairment in neurofibromatosis type 1. Am J Med Genet. 1999, 89: 45-52. 10.1002\/(SICI)1096-8628(19990326)89:1<45::AID-AJMG9>3.0.CO;2-J.","journal-title":"Am J Med Genet"},{"key":"227_CR4","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/S0090-3019(97)00356-X","volume":"51","author":"MM Feldkamp","year":"1999","unstructured":"Feldkamp MM, Angelov L, Guha A: Neurofibromatosis type 1 peripheral nerve tumors: aberrant activation of the Ras pathway. Surg Neurol. 1999, 51: 211-218. 10.1016\/S0090-3019(97)00356-X.","journal-title":"Surg Neurol"},{"key":"227_CR5","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1038\/nature711","volume":"415","author":"RM Costa","year":"2002","unstructured":"Costa RM, Federov NB, Kogan JH, Murphy GG, Stern J, Ohno M, Kucherlapati R, Jacks T, Silva AJ: Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature. 2002, 415: 526-530. 10.1038\/nature711.","journal-title":"Nature"},{"key":"227_CR6","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1126\/science.276.5313.795","volume":"276","author":"HF Guo","year":"1997","unstructured":"Guo HF, The I, Hannan F, Bernards A, Zhong Y: Requirement of Drosophila NF1 for activation of adenylyl cyclase by PACAP38-like neuropeptides. Science. 1997, 276: 795-798. 10.1126\/science.276.5313.795.","journal-title":"Science"},{"key":"227_CR7","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/nn792","volume":"5","author":"J Tong","year":"2002","unstructured":"Tong J, Hannan F, Zhu Y, Bernards A, Zhong Y: Neurofibromin regulates G protein-stimulated adenylyl cyclase activity. Nat Neurosci. 2002, 5: 95-96. 10.1038\/nn792.","journal-title":"Nat Neurosci"},{"key":"227_CR8","doi-asserted-by":"crossref","first-page":"8949","DOI":"10.1523\/JNEUROSCI.23-26-08949.2003","volume":"23","author":"B Dasgupta","year":"2003","unstructured":"Dasgupta B, Dugan LL, Gutmann DH: The neurofibromatosis 1 gene product neurofibromin regulates pituitary adenylate cyclase-activating polypeptide-mediated signaling in astrocytes. J of Neurosci. 2003, 23: 8949-8954.","journal-title":"J of Neurosci"},{"key":"227_CR9","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1126\/science.276.5313.791","volume":"276","author":"I The","year":"1997","unstructured":"The I, Hannigan GE, Cowley GS, Reginald S, Zhong Y, Gusella JF, Hariharan IK, Bernards A: Rescue of a Drosophila NF1 mutant phenotype by Protein Kinase A. Science. 1997, 276: 791-794. 10.1126\/science.276.5313.791.","journal-title":"Science"},{"key":"227_CR10","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/35002593","volume":"403","author":"HF Guo","year":"2000","unstructured":"Guo HF, Tong J, Hannan F, Luo L, Zhong Y: A neurofibromatosis-1-regulated pathway is required for learning in Drosophila. Nature. 2000, 403: 895-898. 10.1038\/35002593.","journal-title":"Nature"},{"key":"227_CR11","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/ng0794-353","volume":"7","author":"T Jacks","year":"1994","unstructured":"Jacks T, Shih TS, Schmitt EM, Bronson RT, Bernards A, Weinberg RA: Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nat Genet. 1994, 7: 353-61. 10.1038\/ng0794-353.","journal-title":"Nat Genet"},{"key":"227_CR12","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1006\/scbi.1996.0037","volume":"7","author":"K Cichowski","year":"1996","unstructured":"Cichowski K, Shih TS, Jacks T: Nf1 gene targeting: toward models and mechanisms. Sem in Can Bio. 1996, 7: 291-298. 10.1006\/scbi.1996.0037.","journal-title":"Sem in Can Bio"},{"key":"227_CR13","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/S0959-4388(00)00128-8","volume":"10","author":"KC Martin","year":"2000","unstructured":"Martin KC, barad M, Kandel ER: Local protein synthesis and is role in synaose-specific plasticity. Curr OpinNeurobiol. 2000, 10: 587-592. 10.1016\/S0959-4388(00)00128-8.","journal-title":"Curr OpinNeurobiol"},{"key":"227_CR14","unstructured":"Translational Genomics Research Institute. [http:\/\/www.tgen.org\/neurogenomic\/data]"},{"key":"227_CR15","unstructured":"NIH Neuroscience Microarray Consortium. [http:\/\/arrayconsortium.tgen.org]"},{"key":"227_CR16","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1203\/01.PDR.0000049517.47493.E9","volume":"53","author":"MV Johnston","year":"2003","unstructured":"Johnston MV, Alemi L, Harum KH: Learning, memory, and transcription factors. Ped Res. 2003, 53: 369-374. 10.1203\/01.PDR.0000049517.47493.E9.","journal-title":"Ped Res"},{"key":"227_CR17","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1016\/S0006-291X(03)00048-2","volume":"301","author":"K Ueda","year":"2003","unstructured":"Ueda K, Ohta Y, Hosoya H: The carboxy-terminal pleckstrin homology domain of ROCK interacts with filamin-A. Biochem Biophys Res Commun. 2003, 301: 886-90. 10.1016\/S0006-291X(03)00048-2.","journal-title":"Biochem Biophys Res Commun"},{"key":"227_CR18","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/317073a0","volume":"317","author":"ST Brady","year":"1985","unstructured":"Brady ST: A novel brain ATPase with properties expected for the fast axonal transport motor. Nature. 1985, 317: 73-75. 10.1038\/317073a0.","journal-title":"Nature"},{"key":"227_CR19","volume-title":"J Invest Dermatol","author":"S De Schepper","year":"2006","unstructured":"De Schepper S, Boucneau JM, Westbroek W, Mommaas M, Onderwater J, Messiaen L, Naeyaert JM, Lambert JL: Neurofibromatosis Type 1 Protein and Amyloid Precursor Protein Interact in Normal Human Melanocytes and Colocalize with Melanosomes. J Invest Dermatol. 2006, [Epub ahead of print]"},{"key":"227_CR20","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1124\/mol.52.3.508","volume":"52","author":"SW Robinson","year":"1997","unstructured":"Robinson SW, Caron MG: Selective inhibition of adenylate cyclase type V by the dopamine D3 receptor. Mol Pharmaco. 1997, 52: 508-514.","journal-title":"Mol Pharmaco"},{"key":"227_CR21","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1038\/sj.bjp.0702905","volume":"128","author":"PG Zaworski","year":"1999","unstructured":"Zaworski PG, Alberts GL, Pregenzer JF, Im WB, Slightom JL, Gill GS: Efficient functional coupling of the human D3 dopamine receptor to Go subtype of G proteins in SH-SY5Y cells. Brt J of Pharmac. 1999, 128: 1181-1188. 10.1038\/sj.bjp.0702905.","journal-title":"Brt J of Pharmac"},{"key":"227_CR22","unstructured":"Jackson Laboratory. [http:\/\/www.jax.org]"},{"issue":"5","key":"227_CR23","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1158\/0008-5472.CAN-04-2463","volume":"65","author":"MB Mintz","year":"2005","unstructured":"Mintz MB, Sowers R, Brown KM, Hilmer SC, Mazza B, Huvos AG, Meyers PA, Lafleur B, McDonough WS, Henry MM, Ramsey KE, Antonescu CR, Chen W, Healey JH, Daluski A, Berens ME, Macdonald TJ, Gorlick R, Stephan DA: An expression signature classifies chemotherapy-resistant pediatric osteosarcoma. Cancer Res. 2005, 65 (5): 1748-54. 10.1158\/0008-5472.CAN-04-2463.","journal-title":"Cancer Res"},{"key":"227_CR24","first-page":"4190","volume":"61","author":"L Mariani","year":"2001","unstructured":"Mariani L, McDonough WS, Hoelzinger DB, Beaudry C, Kaczmarek E, Coons SW, Giese A, Moghaddam M, Seiler RW, Berens ME: Identification and validation of P311 as a glioblastoma invasion gene using laser capture microdissection. Cancer Res. 2001, 61: 4190-4196.","journal-title":"Cancer Res"},{"key":"227_CR25","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1016\/S0002-9440(10)65059-6","volume":"156","author":"U Lehmann","year":"2000","unstructured":"Lehmann U, Gloeckner S, Kleeberger W, von Wasielevsky HFR, Kreipe H: Detection of gene amplification in archival breast cancer specimens by laser-assisted microdissection and quantitative real-time polymerase chain reaction. Am Pathol. 2000, 156: 1855-1864.","journal-title":"Am Pathol"}],"container-title":["BMC Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2202-7-22.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T02:21:12Z","timestamp":1630462872000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurosci.biomedcentral.com\/articles\/10.1186\/1471-2202-7-22"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3,8]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,12]]}},"alternative-id":["227"],"URL":"https:\/\/doi.org\/10.1186\/1471-2202-7-22","relation":{},"ISSN":["1471-2202"],"issn-type":[{"value":"1471-2202","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,3,8]]},"assertion":[{"value":"3 November 2005","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2006","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2006","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"22"}}