{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:32:48Z","timestamp":1791192768933,"version":"4.1.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2013,7,3]],"date-time":"2013-07-03T00:00:00Z","timestamp":1372809600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0068722","type":"journal-article","created":{"date-parts":[[2013,7,4]],"date-time":"2013-07-04T05:48:54Z","timestamp":1372916934000},"page":"e68722","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":54,"title":["The Impact of Bdnf Gene Deficiency to the Memory Impairment and Brain Pathology of APPswe\/PS1dE9 Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.1371","volume":"8","author":[{"given":"Tomi","family":"Rantam\u00e4ki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Kemppainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Autio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saara","family":"Stav\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hennariikka","family":"Koivisto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Antila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasi O.","family":"Miettinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"K\u00e4rkk\u00e4inen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Karpova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liisa","family":"Vesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"Lindemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius C.","family":"Hoener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"Tanila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eero","family":"Castr\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,7,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.nbd.2006.08.017","article-title":"Characterization of amyloid deposition in the APPswe\/PS1dE9 mouse model of Alzheimer disease","volume":"24","author":"M Garcia-Alloza","year":"2006","journal-title":"Neurobiol Dis"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.nbd.2004.10.022","article-title":"Episodic-like memory deficits in the APPswe\/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities","volume":"18","author":"A Savonenko","year":"2005","journal-title":"Neurobiol Dis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1111\/j.1471-4159.2007.05147.x","article-title":"Age-related decrease in stimulated glutamate release and vesicular glutamate transporters in APP\/PS1 transgenic and wild-type mice","volume":"105","author":"R Minkeviciene","year":"2008","journal-title":"J Neurochem"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1001\/archneur.65.11.1509","article-title":"Frequent amyloid deposition without significant cognitive impairment among the elderly","volume":"65","author":"HJ Aizenstein","year":"2008","journal-title":"Arch Neurol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"198.e1","DOI":"10.1016\/j.neurobiolaging.2010.06.015","article-title":"Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer\u2019s disease","volume":"33","author":"A Kadir","year":"2012","journal-title":"Neurobiol Aging"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.neuro.24.1.677","article-title":"Neurotrophins: roles in neuronal development and function","volume":"24","author":"EJ Huang","year":"2001","journal-title":"Annu Rev Neurosci"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1523\/JNEUROSCI.06-08-02155.1986","article-title":"Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections","volume":"6","author":"F Hefti","year":"1986","journal-title":"J Neurosci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/329065a0","article-title":"Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor","volume":"329","author":"W Fischer","year":"1987","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"7288","DOI":"10.1523\/JNEUROSCI.17-19-07288.1997","article-title":"Disruption of a single allele of the nerve growth factor gene results in atrophy of basal forebrain cholinergic neurons and memory deficits","volume":"17","author":"KS Chen","year":"1997","journal-title":"J Neurosci"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.neuro.22.1.295","article-title":"Neurotrophins and synaptic plasticity","volume":"22","author":"AK McAllister","year":"1999","journal-title":"Annu Rev Neurosci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/35049004","article-title":"Neurotrophins as synaptic modulators","volume":"2","author":"MM Poo","year":"2001","journal-title":"Nat Rev Neurosci"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1601-183X.2007.00378.x","article-title":"Neurotrophic factors in Alzheimer\u2019s disease: role of axonal transport","volume":"7","author":"K Schindowski","year":"2008","journal-title":"Genes Brain Behav"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1006\/mcne.2001.1016","article-title":"The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer\u2019s disease","volume":"18","author":"M Fahnestock","year":"2001","journal-title":"Mol Cell Neurosci"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/0896-6273(91)90273-3","article-title":"BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer\u2019s disease","volume":"7","author":"HS Phillips","year":"1991","journal-title":"Neuron"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0306-4522(94)90202-X","article-title":"Differential regulation of brain-derived neurotrophic factor and type II calcium\/calmodulin-dependent protein kinase messenger RNA expression in Alzheimer\u2019s disease","volume":"60","author":"KD Murray","year":"1994","journal-title":"Neuroscience"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1097\/00001756-199611250-00024","article-title":"Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer\u2019s disease","volume":"7","author":"M Narisawa-Saito","year":"1996","journal-title":"Neuroreport"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0169-328X(97)00125-3","article-title":"Brain-derived neurotrophic factor is reduced in Alzheimer\u2019s disease","volume":"49","author":"B Connor","year":"1997","journal-title":"Brain Res Mol Brain Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1001\/archneur.57.6.846","article-title":"Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas","volume":"57","author":"C Hock","year":"2000","journal-title":"Arch Neurol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0169-328X(00)00023-1","article-title":"Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: decreased levels in Alzheimer\u2019s disease","volume":"76","author":"RM Holsinger","year":"2000","journal-title":"Brain Res Mol Brain Res"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Fahnestock M, Garzon D, Holsinger RM, Michalski B (2002) Neurotrophic factors and Alzheimer\u2019s disease: are we focusing on the wrong molecule? J Neural Transm Suppl 241\u2013252.","DOI":"10.1007\/978-3-7091-6139-5_22"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0169-328X(03)00003-2","article-title":"Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer\u2019s disease","volume":"111","author":"B Michalski","year":"2003","journal-title":"Brain Res Mol Brain Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1111\/j.1471-4159.2005.03135.x","article-title":"Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer\u2019s disease","volume":"93","author":"S Peng","year":"2005","journal-title":"J Neurochem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"9321","DOI":"10.1523\/JNEUROSCI.4736-08.2009","article-title":"Decreased brain-derived neurotrophic factor depends on amyloid aggregation state in transgenic mouse models of Alzheimer\u2019s disease","volume":"29","author":"S Peng","year":"2009","journal-title":"J Neurosci"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S0736-5748(00)00046-0","article-title":"Brain-derived neurotrophic factor and neurotrophin-3 levels in Alzheimer\u2019s disease brains","volume":"18","author":"N Durany","year":"2000","journal-title":"Int J Dev Neurosci"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nrd3366","article-title":"Potential therapeutic uses of BDNF in neurological and psychiatric disorders","volume":"10","author":"AH Nagahara","year":"2011","journal-title":"Nat Rev Drug Discov"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s12031-007-9022-x","article-title":"Transplantation of NGF-gene-modified bone marrow stromal cells into a rat model of Alzheimer\u2019 disease","volume":"34","author":"LY Li","year":"2008","journal-title":"J Mol Neurosci"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nm1239","article-title":"A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease","volume":"11","author":"MH Tuszynski","year":"2005","journal-title":"Nat Med"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nm.1912","article-title":"Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer\u2019s disease","volume":"15","author":"AH Nagahara","year":"2009","journal-title":"Nat Med"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1122.e23","DOI":"10.1016\/j.neurobiolaging.2011.11.006","article-title":"Impaired TrkB receptor signaling contributes to memory impairment in APP\/PS1 mice","volume":"33","author":"S Kemppainen","year":"2012","journal-title":"Neurobiol Aging"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.neurobiolaging.2003.09.008","article-title":"APP processing and amyloid deposition in mice haplo-insufficient for presenilin 1","volume":"25","author":"JL Jankowsky","year":"2004","journal-title":"Neurobiol Aging"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/368147a0","article-title":"Mice lacking brain-derived neurotrophic factor develop with sensory deficits","volume":"368","author":"P Ernfors","year":"1994","journal-title":"Nature"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1046\/j.1471-4159.1999.0721930.x","article-title":"Brain-derived neurotrophic factor levels in the nervous system of wild-type and neurotrophin gene mutant mice","volume":"72","author":"R Kolbeck","year":"1999","journal-title":"J Neurochem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s10571-010-9544-6","article-title":"Darkness reduces BDNF expression in the visual cortex and induces repressive chromatin remodeling at the BDNF gene in both hippocampus and visual cortex","volume":"30","author":"NN Karpova","year":"2010","journal-title":"Cell Mol Neurobiol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1210\/mend.15.10.0706","article-title":"Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity","volume":"15","author":"M Rios","year":"2001","journal-title":"Mol Endocrinol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1038\/sj.npp.1301345","article-title":"Pharmacologically diverse antidepressants rapidly activate brain-derived neurotrophic factor receptor TrkB and induce phospholipase-Cgamma signaling pathways in mouse brain","volume":"32","author":"T Rantam\u00e4ki","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"7539","DOI":"10.1523\/JNEUROSCI.15-11-07539.1995","article-title":"Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments","volume":"15","author":"M Nibuya","year":"1995","journal-title":"J Neurosci"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nn2038","article-title":"Biosynthesis and processing of endogenous BDNF: CNS neurons store and secrete BDNF, not pro-BDNF","volume":"11","author":"T Matsumoto","year":"2008","journal-title":"Nat Neurosci"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.neuron.2006.03.044","article-title":"Cell survival through Trk neurotrophin receptors is differentially regulated by ubiquitination","volume":"50","author":"JC Arevalo","year":"2006","journal-title":"Neuron"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"e20567","DOI":"10.1371\/journal.pone.0020567","article-title":"Antidepressant drugs transactivate TrkB neurotrophin receptors in the adult rodent brain independently of BDNF and monoamine transporter blockade","volume":"6","author":"T Rantam\u00e4ki","year":"2011","journal-title":"PLoS One"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e32869","DOI":"10.1371\/journal.pone.0032869","article-title":"The Responsiveness of TrkB to BDNF and Antidepressant Drugs Is Differentially Regulated during Mouse Development","volume":"7","author":"A Di Lieto","year":"2012","journal-title":"PLoS One"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.euroneuro.2008.09.002","article-title":"Long-lasting behavioural and molecular alterations induced by early postnatal fluoxetine exposure are restored by chronic fluoxetine treatment in adult mice","volume":"19","author":"NN Karpova","year":"2009","journal-title":"Eur Neuropsychopharmacol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nature05957","article-title":"Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo","volume":"448","author":"P Lindholm","year":"2007","journal-title":"Nature"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1093\/emboj\/19.6.1290","article-title":"BDNF regulates eating behavior and locomotor activity in mice","volume":"19","author":"SG Kernie","year":"2000","journal-title":"EMBO J"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1523\/JNEUROSCI.5599-03.2004","article-title":"Induction of brain-derived neurotrophic factor in plaque-associated glial cells of aged APP23 transgenic mice","volume":"24","author":"GJ Burbach","year":"2004","journal-title":"J Neurosci"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.nbd.2004.04.010","article-title":"Late onset loss of hippocampal 5-HT and NE is accompanied by increases in BDNF protein expression in mice co-expressing mutant APP and PS1","volume":"16","author":"ME Szapacs","year":"2004","journal-title":"Neurobiol Dis"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/j.1601-183X.2012.00784.x","article-title":"Reduction of BDNF expression in Fmr1 knockout mice worsens cognitive deficits but improves hyperactivity and sensorimotor deficits","volume":"11","author":"M Uutela","year":"2012","journal-title":"Genes Brain Behav"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1097\/00005072-199907000-00007","article-title":"BDNF and full-length and truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies","volume":"58","author":"I Ferrer","year":"1999","journal-title":"J Neuropathol Exp Neurol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"17301","DOI":"10.1074\/jbc.M010450200","article-title":"Beta -amyloid-(1\u201342) impairs activity-dependent cAMP-response element-binding protein signaling in neurons at concentrations in which cell survival Is not compromised","volume":"276","author":"L Tong","year":"2001","journal-title":"J Biol Chem"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/S0306-4522(98)00219-X","article-title":"An immunohistochemical study of the distribution of brain-derived neurotrophic factor in the adult human brain, with particular reference to Alzheimer\u2019s disease","volume":"88","author":"MG Murer","year":"1999","journal-title":"Neuroscience"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"e39566","DOI":"10.1371\/journal.pone.0039566","article-title":"Genetic knockdown of brain-derived neurotrophic factor in 3xTg-AD mice does not alter Abeta or tau pathology","volume":"7","author":"NA Castello","year":"2012","journal-title":"PLoS One"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0068722","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T02:55:14Z","timestamp":1563332114000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0068722"}},"subtitle":[],"editor":[{"given":"Maya","family":"Koronyo-Hamaoui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,7,3]]},"references-count":50,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2013,7,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0068722","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,3]]}}}