{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:20:00Z","timestamp":1790824800303,"version":"4.1.0"},"reference-count":79,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-Aid for Scientific Research C","award":["23K06348"],"award-info":[{"award-number":["23K06348"]}]},{"name":"Grants-in-Aid for Scientific Research C","award":["16H05129"],"award-info":[{"award-number":["16H05129"]}]},{"name":"Grants-in-Aid for Scientific Research C","award":["19H03402"],"award-info":[{"award-number":["19H03402"]}]},{"name":"Grants-in-Aid for Scientific Research C","award":["26115518"],"award-info":[{"award-number":["26115518"]}]},{"DOI":"10.13039\/501100000646","name":"Scientific Research B","doi-asserted-by":"publisher","award":["23K06348"],"award-info":[{"award-number":["23K06348"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Scientific Research B","doi-asserted-by":"publisher","award":["16H05129"],"award-info":[{"award-number":["16H05129"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Scientific Research B","doi-asserted-by":"publisher","award":["19H03402"],"award-info":[{"award-number":["19H03402"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Scientific Research B","doi-asserted-by":"publisher","award":["26115518"],"award-info":[{"award-number":["26115518"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research in Innovative Areas","award":["23K06348"],"award-info":[{"award-number":["23K06348"]}]},{"name":"Scientific Research in Innovative Areas","award":["16H05129"],"award-info":[{"award-number":["16H05129"]}]},{"name":"Scientific Research in Innovative Areas","award":["19H03402"],"award-info":[{"award-number":["19H03402"]}]},{"name":"Scientific Research in Innovative Areas","award":["26115518"],"award-info":[{"award-number":["26115518"]}]},{"name":"YU AI project of the Center for Information and Data Science Education","award":["23K06348"],"award-info":[{"award-number":["23K06348"]}]},{"name":"YU AI project of the Center for Information and Data Science Education","award":["16H05129"],"award-info":[{"award-number":["16H05129"]}]},{"name":"YU AI project of the Center for Information and Data Science Education","award":["19H03402"],"award-info":[{"award-number":["19H03402"]}]},{"name":"YU AI project of the Center for Information and Data Science Education","award":["26115518"],"award-info":[{"award-number":["26115518"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>A\u03b21-42 (amyloid beta) oligomers, the major neurotoxic culprits in Alzheimer\u2019s disease, initiate early pathophysiological events, including neuronal hyperactivity, that underlie aberrant network activity and cognitive impairment. Although several synaptotoxic effects have been extensively studied, neuronal hyperexcitability, which may also contribute to cognitive deficits, is not fully understood. Here, we found several adverse effects of in vivo injection of A\u03b21-42 oligomers on contextual memory and intrinsic properties of CA1 pyramidal neurons. Male rats underwent behavioral and electrophysiological studies 1 week after microinjections into the dorsal CA1 region, followed by histological analysis. After 1 week, A\u03b21-42 oligomers impaired contextual learning without affecting basic physiological functions and triggered training-induced neuronal excitability. Furthermore, riluzole, a persistent sodium current (INaP) blocker, dose-dependently reduced A\u03b21-42 oligomer-induced hyperexcitability. Congo red staining, which detects insoluble amyloid deposits, further identified labeling of CA1 pyramidal neurons while immunohistochemistry with lecanemab, which detects soluble A\u03b2 oligomers, revealed immunoreactivity of both pyramidal and non-pyramidal cells in the target area. Therefore, our study suggests that a single injection of A\u03b21-42 oligomers resulted in contextual memory deficits along with concomitant neuronal hyperexcitability and amyloid deposition in the CA1 region after 1 week.<\/jats:p>","DOI":"10.3390\/biom14111425","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T03:52:07Z","timestamp":1731297127000},"page":"1425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Adverse Effects of A\u03b21-42 Oligomers: Impaired Contextual Memory and Altered Intrinsic Properties of CA1 Pyramidal Neurons"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6953-9599","authenticated-orcid":false,"family":"Min-Kaung-Wint-Mon","sequence":"first","affiliation":[{"name":"Department of Physiology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kida","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itsuki","family":"Kanehisa","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Kurose","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Sakimoto","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Paw-Min-Thein-Oo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoichi","family":"Kimura","sequence":"additional","affiliation":[{"name":"Center for Liberal Arts and Sciences, Sanyo-Onoda City University, Sanyo-Onoda 756-0884, Yamaguchi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-7714","authenticated-orcid":false,"given":"Dai","family":"Mitsushima","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan"},{"name":"The Research Institute for Time Studies, Yamaguchi University, Yamaguchi 753-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease: Progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1038\/s41593-020-0687-6","article-title":"Synergy between amyloid-\u03b2 and tau in Alzheimer\u2019s disease","volume":"23","author":"Busche","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.neurobiolaging.2003.08.012","article-title":"Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer\u2019s disease","volume":"24","author":"Oddo","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1074\/jbc.M507892200","article-title":"Temporal profile of amyloid-\u03b2 (A\u03b2) oligomerization in an in vivo model of Alzheimer disease","volume":"281","author":"Oddo","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1111\/j.1471-4159.2007.04607.x","article-title":"Genetically augmenting tau levels does not modulate the onset or progression of A\u03b2 pathology in transgenic mice","volume":"102","author":"Oddo","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1001\/jamaneurol.2019.1424","article-title":"Association of amyloid and tau with cognition in preclinical Alzheimer disease: A longitudinal study","volume":"76","author":"Hanseeuw","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1126\/science.286.5440.735","article-title":"\u03b2-secretase cleavage of Alzheimer\u2019s amyloid precursor protein by the transmembrane aspartic protease BACE","volume":"286","author":"Vassar","year":"1999","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3233\/JAD-2009-0957","article-title":"\u03b3-secretase catalyzes sequential cleavages of the A\u03b2pp transmembrane domain","volume":"16","author":"Xu","year":"2009","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7013","DOI":"10.1074\/jbc.270.13.7013","article-title":"Amyloid \u03b2 protein (A\u03b2) in Alzheimer\u2019s disease brain","volume":"270","author":"Gravina","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1073\/pnas.222681699","article-title":"Amyloid \u03b2-protein (A\u03b2) assembly: A\u03b240 and A\u03b242 oligomerize through distinct pathways","volume":"100","author":"Bitan","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.jmb.2008.09.039","article-title":"Amyloid \u03b2-protein monomer folding: Free-energy surfaces reveal alloform-specific differences","volume":"384","author":"Yang","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nsmb.1799","article-title":"Structural conversion of neurotoxic amyloid-\u03b21\u201342 oligomers to fibrils","volume":"17","author":"Ahmed","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1046\/j.1460-9568.2003.02444.x","article-title":"Age-dependent cognitive decline in the APP23 model precedes amyloid deposition","volume":"17","author":"Staufenbiel","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4050","DOI":"10.1523\/JNEUROSCI.20-11-04050.2000","article-title":"High-level neuronal expression of A\u03b2 1\u201342 in wild-type human amyloid protein precursor transgenic mice: Synaptotoxicity without plaque formation","volume":"20","author":"Mucke","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/ana.22052","article-title":"Days to criterion as an indicator of toxicity associated with human Alzheimer amyloid-\u03b2 oligomers","volume":"68","author":"Gandy","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1074\/jbc.271.8.4077","article-title":"Water-soluble A\u03b2 (N-40, N-42) oligomers in normal and Alzheimer disease brains","volume":"271","author":"Kuo","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20631","DOI":"10.1074\/jbc.271.34.20631","article-title":"Morphology and toxicity of A\u03b2-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer\u2019s disease","volume":"271","author":"Roher","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10417","DOI":"10.1073\/pnas.1834302100","article-title":"Alzheimer\u2019s disease-affected brain: Presence of oligomeric A\u03b2 ligands (ADDLs) suggests a molecular basis for reversible memory loss","volume":"100","author":"Gong","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13629","DOI":"10.1523\/JNEUROSCI.1353-14.2014","article-title":"Alzheimer\u2019s disease-like pathology induced by amyloid-\u03b2 oligomers in nonhuman Primates","volume":"34","author":"Batista","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrm2101","article-title":"Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer\u2019s amyloid \u03b2-peptide","volume":"8","author":"Haass","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s00441-017-2744-3","article-title":"The storage and recall of memories in the hippocampo-cortical system","volume":"373","author":"Rolls","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1515\/REVNEURO.2004.15.5.333","article-title":"A behavioral assessment of hippocampal function based on a subregional analysis","volume":"15","author":"Kesner","year":"2004","journal-title":"Rev. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nn790","article-title":"Differential contribution of NMDA receptors in hippocampal subregions to spatial working memory","volume":"5","author":"Lee","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nature02965","article-title":"Role for a cortical input to hippocampal area CA1 in the consolidation of a long-term memory","volume":"431","author":"Remondes","year":"2004","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/hipo.10177","article-title":"Differential contributions of dorsal hippocampal subregions to memory acquisition and retrieval in contextual fear-conditioning","volume":"14","author":"Lee","year":"2004","journal-title":"Hippocampus"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"12503","DOI":"10.1073\/pnas.1104558108","article-title":"Contextual learning requires synaptic AMPA receptor delivery in the hippocampus","volume":"108","author":"Mitsushima","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1152\/jn.00278.2019","article-title":"Object and place information processing by CA1 hippocampal neurons of C57BL\/6J mice","volume":"123","author":"Cohen","year":"2020","journal-title":"J. Neurophysiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1111\/ejn.12876","article-title":"Stereological estimation of neuron number and plaque load in the hippocampal region of a transgenic rat model of A lzheimer\u2019s disease","volume":"41","author":"Heggland","year":"2015","journal-title":"Eur. J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1002\/hipo.22403","article-title":"Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous amyloid \u03b2 peptide","volume":"25","author":"Tamagnini","year":"2015","journal-title":"Hippocampus"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e13455","DOI":"10.1111\/acel.13455","article-title":"Synaptic dysregulation and hyperexcitability induced by intracellular amyloid beta oligomers","volume":"20","author":"Peters","year":"2021","journal-title":"Aging Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.neuroscience.2015.07.087","article-title":"Alterations in CA1 pyramidal neuronal intrinsic excitability mediated by Ih channel currents in a rat model of amyloid beta pathology","volume":"305","author":"Eslamizade","year":"2015","journal-title":"Neuroscience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"816174","DOI":"10.3389\/fnins.2022.816174","article-title":"Mitigating effect of estrogen in Alzheimer\u2019s disease-mimicking cerebral organoid","volume":"16","author":"Kim","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11612","DOI":"10.1074\/jbc.M210207200","article-title":"In vitro characterization of conditions for amyloid-\u03b2 Peptide oligomerization and fibrillogenesis","volume":"278","author":"Stine","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7199","DOI":"10.1038\/s41598-022-10453-z","article-title":"A critical period for learning and plastic changes at hippocampal CA1 synapses","volume":"12","author":"Sakimoto","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/0091-3057(86)90195-4","article-title":"Effects of scopolamine and unilateral lesions of the basal forebrain on T-maze spatial discrimination and alternation in rats","volume":"24","author":"Beninger","year":"1986","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/0306-4522(96)00161-3","article-title":"Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice","volume":"74","author":"Yamada","year":"1996","journal-title":"Neuroscience"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.bbr.2013.05.035","article-title":"Use of the light\/dark test for anxiety in adult and adolescent male rats","volume":"256","author":"Arrant","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"539","DOI":"10.5607\/en.2018.27.6.539","article-title":"Striatal inhibition of MeCP2 or TSC1 produces sociability deficits and repetitive behaviors","volume":"27","author":"Lee","year":"2018","journal-title":"Exp. Neurobiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3738","DOI":"10.1038\/srep03738","article-title":"Developmental trajectory of contextual learning and 24-h acetylcholine release in the hippocampus","volume":"4","author":"Takase","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Koppensteiner, P., Trinchese, F., F\u00e0, M., Puzzo, D., Gulisano, W., Yan, S., Poussin, A., Liu, S., Orozco, I., and Dale, E. (2016). Time-dependent reversal of synaptic plasticity induced by physiological concentrations of oligomeric A\u03b242: An early index of Alzheimer\u2019s disease. Sci. Rep., 6.","DOI":"10.1038\/srep32553"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"56","DOI":"10.55782\/ane-2010-1774","article-title":"The relationship between pain sensitivity and conditioned fear response in rats","volume":"70","author":"Lehner","year":"2010","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_42","first-page":"55876","article-title":"Slice patch clamp technique for analyzing learning-induced plasticity","volume":"129","author":"Kida","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_43","unstructured":"Paxinos, G., and Watson, C. (2006). The Rat Bain in Stereotaxic Coordinates, Academic Press. [6th ed.]."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e45250","DOI":"10.1371\/journal.pone.0045250","article-title":"The neuron-astrocyte-microglia triad in normal brain ageing and in a model of neuroinflammation in the rat hippocampus","volume":"7","author":"Cerbai","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3389\/fnagi.2017.00296","article-title":"Alterations in the interplay between neurons, astrocytes and microglia in the rat dentate gyrus in experimental models of neurodegeneration","volume":"9","author":"Lana","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1042\/BCJ20200290","article-title":"Rationally designed peptide-based inhibitor of A\u03b242 fibril formation and toxicity: A potential therapeutic strategy for Alzheimer\u2019s disease","volume":"477","author":"Horsley","year":"2020","journal-title":"Biochem. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1038\/nprot.2006.277","article-title":"Quantification of cerebral amyloid angiopathy and parenchymal amyloid plaques with Congo red histochemical stain","volume":"1","author":"Wilcock","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/1873-3468.12590","article-title":"Amyloidogenicity and toxicity of the reverse and scrambled variants of amyloid-\u03b2 1-42","volume":"591","author":"Vadukul","year":"2017","journal-title":"FEBS Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"30182","DOI":"10.1038\/srep30182","article-title":"A critical role for the self-assembly of amyloid-\u03b21-42 in neurodegeneration","volume":"6","author":"Marshall","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"183337","DOI":"10.1016\/j.bbamem.2020.183337","article-title":"The monomers, oligomers, and fibrils of amyloid-\u03b2 inhibit the activity of mitoBKCa channels by a membrane-mediated mechanism","volume":"1862","author":"Kravenska","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/(SICI)1097-4547(19990815)57:4<458::AID-JNR5>3.0.CO;2-4","article-title":"Alzheimer amyloid abeta1-42 channels: Effects of solvent, pH, and Congo Red","volume":"57","author":"Hirakura","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/npp.2009.207","article-title":"Treatment strategies targeting excess hippocampal activity benefit aged rats with cognitive Impairment","volume":"35","author":"Koh","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.neuroimage.2010.03.040","article-title":"High-resolution structural and functional MRI of hippocampal CA3 and dentate gyrus in patients with amnestic Mild Cognitive Impairment","volume":"51","author":"Yassa","year":"2010","journal-title":"NeuroImage"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41598-017-18729-5","article-title":"Amyloid \u03b2 causes excitation\/inhibition imbalance through dopamine receptor 1-dependent disruption of fast-spiking GABAergic input in anterior cingulate cortex","volume":"8","author":"Ren","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1523\/JNEUROSCI.0876-20.2020","article-title":"Implications of oligomeric amyloid-beta (oA\u03b242) signaling through \u03b17\u03b22-nicotinic acetylcholine receptors (nAChRs) on basal forebrain cholinergic neuronal intrinsic excitability and cognitive decline","volume":"41","author":"George","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9162","DOI":"10.1523\/JNEUROSCI.2454-05.2005","article-title":"Differential expression of TASK channels between horizontal interneurons and pyramidal cells of rat hippocampus","volume":"25","author":"Taverna","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1113\/jphysiol.2002.029249","article-title":"Two forms of electrical resonance at theta frequencies, generated by M-current, h-current and persistent Na+ current in rat hippocampal pyramidal cells","volume":"545","author":"Hu","year":"2002","journal-title":"J. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9905","DOI":"10.1038\/s41598-018-28232-0","article-title":"Dependence and homeostasis of membrane impedance on cell morphology in cultured hippocampal neurons","volume":"8","author":"Matsumura","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"25841","DOI":"10.1038\/srep25841","article-title":"Amyloid beta oligomers induce neuronal elasticity changes in age-dependent manner: A force spectroscopy study on living hippocampal neurons","volume":"6","author":"Ungureanu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"17294","DOI":"10.1074\/jbc.M500997200","article-title":"Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers","volume":"280","author":"Demuro","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1523\/JNEUROSCI.4771-07.2008","article-title":"Amyloid \u03b2 oligomers (A\u03b21\u201342 globulomer) suppress spontaneous synaptic activity by inhibition of P\/Q-Type calcium currents","volume":"28","author":"Nimmrich","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5180","DOI":"10.1038\/s41598-019-41526-1","article-title":"GluR2 endocytosis-dependent protein degradation in the amygdala mediates memory updating","volume":"9","author":"Ferrara","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1043664","DOI":"10.3389\/fnsys.2023.1043664","article-title":"Endocytosis is required for consolidation of pattern-separated memories in the perirhinal cortex","volume":"17","author":"Miranda","year":"2023","journal-title":"Front. Syst. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"11100","DOI":"10.1523\/JNEUROSCI.6752-10.2011","article-title":"Suppression of a neocortical potassium channel activity by intracellular amyloid-\u03b2 and its rescue with Homer1a","volume":"31","author":"Yamamoto","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13592","DOI":"10.1038\/s41598-019-50018-1","article-title":"Amyloid \u03b2-induced upregulation of Nav1.6 underlies neuronal hyperactivity in Tg2576 Alzheimer\u2019s disease mouse model","volume":"9","author":"Ciccone","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"19590","DOI":"10.1074\/jbc.M115.691840","article-title":"Amyloid-\u03b2 (1-42) aggregation initiates its cellular uptake and cytotoxicity","volume":"291","author":"Jin","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00424-010-0801-9","article-title":"Biophysical characterisation of the persistent sodium current of the Nav1.6 neuronal sodium channel: A single-channel analysis","volume":"460","author":"Chatelier","year":"2010","journal-title":"Pfl\u00fcgers Arch.-Eur. J. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2005.12.022","article-title":"Contrasting effects of the persistent Na+ current on neuronal excitability and spike timing","volume":"49","author":"Vervaeke","year":"2006","journal-title":"Neuron"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.neulet.2014.07.050","article-title":"Persistent sodium currents contribute to A\u03b21-42-induced hyperexcitation of hippocampal CA1 pyramidal neurons","volume":"580","author":"Ren","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_70","unstructured":"Kimura, R., and Mitsuhsima, D. (2025). Riluzole improves hippocampus-dependent learning deficits caused by A\u03b21\u201342 oligomers. Abstract for the 102nd Annual Meeting of the Physiological Society of Japan. J. Physiol. Sci., 75, in press."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.neuroscience.2007.04.011","article-title":"\u03b2-Amyloid pathology in the entorhinal cortex of rats induces memory deficits: Implications for Alzheimer\u2019s disease","volume":"147","author":"Sipos","year":"2007","journal-title":"Neuroscience"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.neuint.2018.09.005","article-title":"Activation of \u03b17 nicotinic acetylcholine receptor alleviates A\u03b21-42-induced neurotoxicity via downregulation of p38 and JNK MAPK signaling pathways","volume":"120","author":"Chang","year":"2008","journal-title":"Neurochem. Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.expneurol.2007.10.009","article-title":"A\u03b2 (1\u201342) injection causes memory impairment, lowered cortical and serum BDNF levels, and decreased hippocampal 5-HT2A levels","volume":"210","author":"Christensen","year":"2008","journal-title":"Exp. Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7852","DOI":"10.1523\/JNEUROSCI.5901-11.2012","article-title":"Neurotoxicity and memory deficits induced by soluble low-molecular-weight amyloid- 1-42 oligomers are revealed in vivo by using a novel animal model","volume":"32","author":"Brouillette","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.neuropharm.2018.03.007","article-title":"Rhynchophylline suppresses soluble A\u03b21-42-induced impairment of spatial cognition function via inhibiting excessive activation of extrasynaptic NR2B-containing NMDA receptors","volume":"135","author":"Yang","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3109\/13506129.2012.755122","article-title":"Intrahippocampal injection of A\u03b2 1-42 inhibits neurogenesis and down-regulates IFN-\u03b3 and NF-\u03baB expression in hippocampus of adult mouse brain","volume":"20","author":"Zheng","year":"2013","journal-title":"Amyloid"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s13311-022-01308-6","article-title":"Lecanemab, Aducanumab, and Gantenerumab-binding profiles to different forms of amyloid-Beta might explain efficacy and side effects in clinical trials for Alzheimer\u2019s disease","volume":"20","author":"Johannesson","year":"2023","journal-title":"Neurotherapeutics"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0006-8993(98)01002-6","article-title":"Delayed behavioral effects following intrahippocampal injection of aggregated A\u03b2 (1\u201342)","volume":"815","author":"Weldon","year":"1999","journal-title":"Brain Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat. Protoc."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/11\/1425\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:29:00Z","timestamp":1760113740000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/11\/1425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,8]]},"references-count":79,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["biom14111425"],"URL":"https:\/\/doi.org\/10.3390\/biom14111425","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,8]]}}}