{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:27:00Z","timestamp":1790832420455,"version":"4.1.0"},"reference-count":122,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001543","name":"Neurological Foundation of New Zealand","doi-asserted-by":"publisher","award":["1835-PG"],"award-info":[{"award-number":["1835-PG"]}],"id":[{"id":"10.13039\/501100001543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["16-597"],"award-info":[{"award-number":["16-597"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Anatomy, University of Otago, New Zealand","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Synaptic plasticity events, including long-term potentiation (LTP), are often regarded as correlates of brain functions of memory and cognition. One of the central players in these plasticity-related phenomena is the \u03b1-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR). Increased levels of AMPARs on postsynaptic membranes thus constitute a biochemical measure of LTP. Isolated synaptic terminals (synaptosomes) are an excellent ex vivo tool to monitor synaptic physiology in healthy and diseased brains, particularly in human research. We herein describe three protocols for chemically-induced LTP (cLTP) in synaptosomes from both rodent and human brain tissues. Two of these chemical stimulation protocols are described for the first time in synaptosomes. A pharmacological block of synaptosomal actin dynamics confirmed the efficiency of the cLTP protocols. Furthermore, the study prototypically evaluated the deficiency of cLTP in cortical synaptosomes obtained from human cases of early-onset Alzheimer\u2019s disease (EOAD) and frontotemporal lobar degeneration (FLTD), as well as an animal model that mimics FLTD.<\/jats:p>","DOI":"10.3390\/cells10051174","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T10:59:12Z","timestamp":1620817152000},"page":"1174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Chemical Stimulation of Rodent and Human Cortical Synaptosomes: Implications in Neurodegeneration"],"prefix":"10.3390","volume":"10","author":[{"given":"Faraz","family":"Ahmad","sequence":"first","affiliation":[{"name":"Department of Anatomy, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5066-4150","authenticated-orcid":false,"given":"Albert","family":"Llad\u00f3","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Cl\u00ednic, Institut Investigaci\u00f3 Biom\u00e8dica August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrn3677","article-title":"Hippocampal synaptic plasticity, spatial memory and anxiety","volume":"15","author":"Bannerman","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a005751","DOI":"10.1101\/cshperspect.a005751","article-title":"Synapses and memory storage","volume":"4","author":"Mayford","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20130288","DOI":"10.1098\/rstb.2013.0288","article-title":"The synaptic plasticity and memory hypothesis: Encoding, storage and persistence","volume":"369","author":"Takeuchi","year":"2014","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.neuron.2018.10.018","article-title":"The AMPA receptor code of synaptic plasticity","volume":"100","author":"Diering","year":"2018","journal-title":"Neuron"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nrn.2016.37","article-title":"Synaptic AMPA receptor composition in development, plasticity and disease","volume":"17","author":"Henley","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.neuron.2013.10.025","article-title":"AMPARs and synaptic plasticity: The last 25 years","volume":"80","author":"Huganir","year":"2013","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.neuron.2009.01.015","article-title":"Synaptic AMPA Receptor Plasticity and Behavior","volume":"61","author":"Kessels","year":"2009","journal-title":"Neuron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3389\/fncel.2018.00286","article-title":"Recent findings on AMPA receptor recycling","volume":"12","author":"Moretto","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev.neuro.25.112701.142758","article-title":"AMPA receptor trafficking and synaptic plasticity","volume":"25","author":"Malinow","year":"2002","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3389\/fncel.2014.00381","article-title":"Actin-dependent mechanisms in AMPA receptor trafficking","volume":"8","author":"Hanley","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"147009","DOI":"10.1016\/j.brainres.2020.147009","article-title":"Synaptosome as a tool in Alzheimer\u2019s disease research","volume":"1746","author":"Ahmad","year":"2020","journal-title":"Brain Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1101\/pdb.top074450","article-title":"The synaptosome as a model system for studying synaptic physiology","volume":"2015","author":"Evans","year":"2015","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Murphy, K.M. (2018). Synaptosomes (Neuromethods 141), Humana Press.","DOI":"10.1007\/978-1-4939-8739-9"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0005-2728(96)00103-X","article-title":"Metabolic and energetic properties of isolated nerve ending particles (synaptosomes)","volume":"1277","author":"Erecinska","year":"1996","journal-title":"Biochim. Biophys. Acta Bioenergy"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s40120-017-0070-z","article-title":"The Study of Postmortem Human Synaptosomes for Understanding Alzheimer\u2019s Disease and Other Neurological Disorders: A Review","volume":"6","author":"Jhou","year":"2017","journal-title":"Neurol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/BF02834357","article-title":"Optimization of freezing, storage, and thawing conditions for the preparation of metabolically active synaptosomes from frozen rat and human brain","volume":"4","author":"Dodd","year":"1986","journal-title":"Neurochem. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hardy, J.A., and Dodd, P.R. (1985). CHAPTER 2\u2014Metabolic and functional studies on post-mortem human brain. Selected Topics from Neurochemistry, Elsevier.","DOI":"10.1016\/B978-0-08-031994-0.50007-4"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/0304-3940(82)90392-5","article-title":"Use of post-mortem human synaptosomes for studies of metabolism and transmitter amino acid release","volume":"33","author":"Hardy","year":"1982","journal-title":"Neurosci. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1111\/j.1471-4159.1983.tb08024.x","article-title":"Metabolically active synaptosomes can be prepared from frozen rat and human brain","volume":"40","author":"Hardy","year":"1983","journal-title":"J. Neurochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1073\/pnas.87.7.2452","article-title":"Regulatory changes in presynaptic cholinergic function assessed in rapid autopsy material from patients with Alzheimer disease: Implications for etiology and therapy","volume":"87","author":"Slotkin","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1007\/s00702-003-0012-z","article-title":"Synaptic vesicle transport and synaptic membrane transporter sites in excitatory amino acid nerve terminals in Alzheimer disease","volume":"110","author":"Westphalen","year":"2003","journal-title":"J. Neural Transm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.neuropharm.2018.07.012","article-title":"Methylene blue activates the PMCA activity and cross-interacts with amyloid \u03b2-peptide, blocking A\u03b2-mediated PMCA inhibition","volume":"139","author":"Berrocal","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ajpath.2015.09.018","article-title":"Synaptic amyloid-\u03b2 oligomers precede p-Tau and differentiate high pathology control cases","volume":"186","author":"Bilousova","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/j.ajpath.2012.06.033","article-title":"The synaptic accumulation of hyperphosphorylated tau oligomers in alzheimer disease is associated with dysfunction of the ubiquitin-proteasome system","volume":"181","author":"Tai","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/jnc.12991","article-title":"Pre-synaptic C-terminal truncated tau is released from cortical synapses in Alzheimer\u2019s disease","volume":"133","author":"Sokolow","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1089\/ars.2016.6860","article-title":"Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer\u2019s Disease","volume":"27","author":"Ahmad","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Williams, C., Shai, R.M., Wu, Y., Hsu, Y.H., Sitzer, T., Spann, B., McCleary, C., Mo, Y., and Miller, C.A. (2009). Transcriptome analysis of synaptoneurosomes identifies neuroplasticity genes overexpressed in incipient Alzheimer\u2019s disease. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004936"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1523\/JNEUROSCI.2127-17.2017","article-title":"A\u03b2 mediates F-actin disassembly in dendritic spines leading to cognitive deficits in alzheimer\u2019s disease","volume":"38","author":"Kommaddi","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10349","DOI":"10.1523\/JNEUROSCI.1409-18.2018","article-title":"Synaptotoxicity in Alzheimer\u2019s disease involved a dysregulation of actin cytoskeleton dynamics through cofilin 1 phosphorylation","volume":"38","author":"Rush","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13119","DOI":"10.1038\/s41598-018-31073-6","article-title":"Isoform-specific hyperactivation of calpain-2 occurs presymptomatically at the synapse in Alzheimer\u2019s disease mice and correlates with memory deficits in human subjects","volume":"8","author":"Ahmad","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.nbd.2007.11.004","article-title":"Loss of phospholipid asymmetry and elevated brain apoptotic protein levels in subjects with amnestic mild cognitive impairment and Alzheimer disease","volume":"29","author":"Cenini","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0304-3940(94)90074-4","article-title":"Phosphoinositide kinase activities in synaptosomes prepared from brains of patients with Alzheimer\u2019s disease and controls","volume":"176","author":"Bothmer","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.trci.2018.01.002","article-title":"Elevated phospholipase D isoform 1 in Alzheimer\u2019s disease patients\u2019 hippocampus: Relevance to synaptic dysfunction and memory deficits","volume":"4","author":"Krishnan","year":"2018","journal-title":"Alzheimers Dement. Transl. Res. Clin. Interv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"833.e1","DOI":"10.1016\/j.neurobiolaging.2011.08.001","article-title":"Interaction between NH2-tau fragment and A\u03b2 in Alzheimer\u2019s disease mitochondria contributes to the synaptic deterioration","volume":"33","author":"Amadoro","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9057","DOI":"10.1523\/JNEUROSCI.1469-06.2006","article-title":"Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer\u2019s disease brain is associated with mitochondrial dysfunction","volume":"26","author":"Devi","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Reddy, P.H., and Oliver, D.M. (2019). Amyloid beta and phosphorylated tau-induced defective autophagy and mitophagy in Alzheimer\u2019s disease. Cells, 8.","DOI":"10.3390\/cells8050488"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Corera, A.T., Doucet, G., and Fon, E.A. (2009). Long-term potentiation in isolated dendritic spines. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006021"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e48143","DOI":"10.15252\/embr.201948143","article-title":"NPC 1 enables cholesterol mobilization during long-term potentiation that can be restored in Niemann\u2013Pick disease type C by CYP 46A1 activation","volume":"20","author":"Mitroi","year":"2019","journal-title":"EMBO Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E5078","DOI":"10.1073\/pnas.1514486112","article-title":"Synapse-specific IL-1 receptor subunit reconfiguration augments vulnerability to IL-1\u03b2 in the aged hippocampus","volume":"112","author":"Prieto","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11064-018-2517-8","article-title":"TNF\u03b1 and IL-1\u03b2 but not IL-18 suppresses hippocampal long-term potentiation directly at the synapse","volume":"44","author":"Prieto","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1523\/JNEUROSCI.2774-16.2016","article-title":"Pharmacological rescue of long-term potentiation in Alzheimer diseased synapses","volume":"37","author":"Prieto","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13217","DOI":"10.1073\/pnas.172504199","article-title":"Amyloid \u03b2-peptide inhibition of the PKA\/CREB pathway and long-term potentiation: Reversibility by drugs that enhance cAMP signaling","volume":"99","author":"Vitolo","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1111\/ejn.12188","article-title":"Social isolation perturbs experience-driven synaptic glutamate receptor subunit 4 delivery in the developing rat barrel cortex","volume":"37","author":"Miyazaki","year":"2013","journal-title":"Eur. J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.cell.2009.02.034","article-title":"Coincident pre- and postsynaptic activation induces dendritic filopodia via neurotrypsin-dependent agrin cleavage","volume":"136","author":"Sokolowska","year":"2009","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1074\/jbc.M509677200","article-title":"Extrasynaptic membrane trafficking regulated by GluR1 serine 845 phosphorylation primes AMPA receptors for long-term potentiation","volume":"281","author":"Oh","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.neuron.2007.08.020","article-title":"Activity-induced protocadherin arcadlin regulates dendritic spine number by triggering N-cadherin endocytosis via TAO2\u03b2 and p38 MAP kinases","volume":"56","author":"Yasuda","year":"2007","journal-title":"Neuron"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6965","DOI":"10.1096\/fj.201902122RR","article-title":"Microtubule-associated protein 2 mediates induction of long-term potentiation in hippocampal neurons","volume":"34","author":"Kim","year":"2020","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/349067a0","article-title":"Novel form of long-term potentiation produced by a K+ channel blocker in the hippocampus","volume":"349","author":"Aniksztejn","year":"1991","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.brainres.2008.09.101","article-title":"TEA-induced long-term potentiation at hippocampal mossy fiber-CA3 synapses: Characteristics of its induction and expression","volume":"1247","author":"Suzuki","year":"2009","journal-title":"Brain Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0304-3940(00)01081-8","article-title":"Activation of pre- and postsynaptic protein kinase C during tetraethylammonium-induced long-term potentiation in the CA1 field of the hippocampus","volume":"286","author":"Ramakers","year":"2000","journal-title":"Neurosci. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0304-3940(00)01715-8","article-title":"Tetraethylammonium-induced long-term potentiation in layer V horizontal connections of rat motor cortex","volume":"298","author":"Jagodzinski","year":"2001","journal-title":"Neurosci. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/cercor\/6.6.771","article-title":"Tetraethylammonium-induced synaptic plasticity in rat neocortex","volume":"6","author":"Pelletier","year":"1996","journal-title":"Cereb. Cortex"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1139\/y91-133","article-title":"Forskolin and phosphodiesterase inhibitors release adenosine but inhibit morphine-evoked release of adenosine from spinal cord synaptosomes","volume":"69","author":"Nicholson","year":"1991","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0028-3908(02)00379-9","article-title":"GABAB receptor-mediated presynaptic potentiation of ATP ionotropic receptors in rat midbrain synaptosomes","volume":"44","author":"Pintor","year":"2003","journal-title":"Neuropharmacology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1523\/JNEUROSCI.05-10-02685.1985","article-title":"Evidence for a presynaptic adenylate cyclase system facilitating [3H]norepinephrine release from rat brain neocortex slices and synaptosomes","volume":"5","author":"Schoffelmeer","year":"1985","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"104482","DOI":"10.1016\/j.nbd.2019.104482","article-title":"The loss of \u03b2 adrenergic receptor mediated release potentiation in a mouse model of fragile X syndrome","volume":"130","author":"Torres","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev.neuro.28.061604.135757","article-title":"The actin cytoskeleton: Integrating form and function at the synapse","volume":"28","author":"Dillon","year":"2005","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-3-7091-0932-8_4","article-title":"Regulation of the actin cytoskeleton in dendritic spines","volume":"970","author":"Penzes","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2014.05.024","article-title":"The structure and function of actin cytoskeleton in mature glutamatergic dendritic spines","volume":"1573","author":"Bellot","year":"2014","journal-title":"Brain Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1152\/physiol.00029.2009","article-title":"The roles of CaMKII and F-Actin in the structural plasticity of dendritic Spines: A potential molecular identity of a synaptic tag?","volume":"24","author":"Okamoto","year":"2009","journal-title":"Physiology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2371970","DOI":"10.1155\/2016\/2371970","article-title":"Regulation of the postsynaptic compartment of excitatory synapses by the actin cytoskeleton in health and its disruption in disease","volume":"2016","author":"Stefen","year":"2016","journal-title":"Neural Plast."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1083\/jcb.201003008","article-title":"Actin in dendritic spines: Connecting dynamics to function","volume":"189","author":"Hotulainen","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/cm.21280","article-title":"Dendritic spine actin dynamics in neuronal maturation and synaptic plasticity","volume":"73","author":"Hlushchenko","year":"2016","journal-title":"Cytoskeleton"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.conb.2010.08.013","article-title":"The dynamic cytoskeleton: Backbone of dendritic spine plasticity","volume":"21","author":"Dent","year":"2011","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S0896-6273(00)80467-5","article-title":"Rapid actin-based plasticity in dendritic spines","volume":"20","author":"Fischer","year":"1998","journal-title":"Neuron"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1038\/nn.2634","article-title":"ADF\/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity","volume":"13","author":"Gu","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1038\/nn1311","article-title":"Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity","volume":"7","author":"Okamoto","year":"2004","journal-title":"Nat. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nn811","article-title":"Rapid turnover of actin in dendritic spines and its regulation by activity","volume":"5","author":"Star","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_69","first-page":"587","article-title":"Developmental neuroplasticity and the origin of neurodegenerative diseases","volume":"17","author":"Schaefers","year":"2016","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Vester, A., and Caudle, W.M. (2016). The synapse as a central target for neurodevelopmental susceptibility to pesticides. Toxics, 4.","DOI":"10.3390\/toxics4030018"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.yfrne.2006.02.001","article-title":"Hippocampal neuroplasticity induced by early-life stress: Functional and molecular aspects","volume":"27","author":"Fenoglio","year":"2006","journal-title":"Front. Neuroendocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.tins.2008.11.007","article-title":"Tau pathophysiology in neurodegeneration: A tangled issue","volume":"32","author":"Stoothoff","year":"2009","journal-title":"Trends Neurosci."},{"key":"ref_73","first-page":"319836","article-title":"Spines, plasticity, and cognition in Alzheimer\u2019s model mice","volume":"2012","author":"Knafo","year":"2012","journal-title":"Neural Plast."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.3233\/JAD-161088","article-title":"Oxidative stress, synaptic dysfunction, and Alzheimer\u2019s disease","volume":"57","author":"Trushina","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.pharmthera.2018.11.006","article-title":"Synaptic dysfunction in Alzheimer\u2019s disease: Mechanisms and therapeutic strategies","volume":"195","author":"Chen","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/cm.21282","article-title":"Actin dynamics and cofilin-actin rods in Alzheimer disease","volume":"73","author":"Bamburg","year":"2016","journal-title":"Cytoskeleton"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.brainresrev.2011.01.003","article-title":"Impaired regulation of synaptic actin cytoskeleton in Alzheimer\u2019s disease","volume":"67","author":"Penzes","year":"2011","journal-title":"Brain Res. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Bardai, F.H., Ordonez, D.G., Bailey, R.M., Hamm, M., Lewis, J., and Feany, M.B. (2018). Lrrk promotes tau neurotoxicity through dysregulation of actin and mitochondrial dynamics. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2006265"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/ncb1528","article-title":"Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo","volume":"9","author":"Fulga","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2016.03.005","article-title":"Acetylated tau obstructs KIBRA-mediated signaling in synaptic plasticity and promotes tauopathy-related memory loss","volume":"90","author":"Tracy","year":"2016","journal-title":"Neuron"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","article-title":"Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model","volume":"53","author":"Yoshiyama","year":"2008","journal-title":"Neuron"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1097\/NEN.0000000000000241","article-title":"Neuroinflammatory gene regulation, mitochondrial function, oxidative stress, and brain lipid modifications with disease progression in tau P301S transgenic mice as a model of frontotemporal lobar degeneration-tau","volume":"74","author":"Aso","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s00726-018-02687-x","article-title":"Altered brain arginine metabolism in a mouse model of tauopathy","volume":"51","author":"Vemula","year":"2019","journal-title":"Amino Acids"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41398-018-0149-z","article-title":"Altered plasma arginine metabolome precedes behavioural and brain arginine metabolomic profile changes in the APPswe\/PS1\u0394E9 mouse model of Alzheimer\u2019s disease","volume":"8","author":"Bergin","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"152492","DOI":"10.1016\/j.tox.2020.152492","article-title":"Developmental lead (Pb)-induced deficits in redox and bioenergetic status of cerebellar synapses are ameliorated by ascorbate supplementation","volume":"440","author":"Ahmad","year":"2020","journal-title":"Toxicology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jneumeth.2017.08.005","article-title":"Proteome profiling of S-nitrosylated synaptosomal proteins by isobaric mass tags","volume":"291","author":"Wijasa","year":"2017","journal-title":"J. Neurosci. Methods"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Plum, S., Eggers, B., Helling, S., Stepath, M., Theiss, C., Leite, R.E.P., Molina, M., Grinberg, L.T., Riederer, P., and Gerlach, M. (2020). Proteomic characterization of synaptosomes from human substantia nigra indicates altered mitochondrial translation in Parkinson\u2019s disease. Cells, 9.","DOI":"10.3390\/cells9122580"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.niox.2019.03.006","article-title":"Altered neurovascular coupling and brain arginine metabolism in endothelial nitric oxide synthase deficient mice","volume":"87","author":"Hariharan","year":"2019","journal-title":"Nitric Oxide Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Forner, S., Martini, A.C., Prieto, G.A., Dang, C.T., Rodriguez-Ortiz, C.J., Reyes-Ruiz, J.M., Trujillo-Estrada, L., da Cunha, C., Andrews, E.J., and Phan, J. (2019). Intra- and extracellular \u03b2-amyloid overexpression via adeno-associated virus-mediated gene transfer impairs memory and synaptic plasticity in the hippocampus. Sci. Rep.","DOI":"10.1038\/s41598-019-52324-0"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1152\/jn.00941.2003","article-title":"Forskolin-induced LTP in the CA1 hippocampal region is NMDA receptor dependent","volume":"91","author":"Otmakhov","year":"2004","journal-title":"J. Neurophysiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"22945","DOI":"10.1074\/jbc.M115.663450","article-title":"Phosphorylation of tyrosine 1070 at the GluN2B subunit is regulated by synaptic activity and critical for surface expression of N-methyl-D-aspartate (NMDA) receptors","volume":"290","author":"Lu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1523\/JNEUROSCI.2463-11.2012","article-title":"RNA binding proteins accumulate at the postsynaptic density with synaptic activity","volume":"32","author":"Zhang","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"jcs234237","DOI":"10.1242\/jcs.234237","article-title":"A retention\u2013release mechanism based on RAB11FIP2 for AMPA receptor synaptic delivery during long-term potentiation","volume":"132","author":"Royo","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1038\/s41598-018-38412-7","article-title":"Neuronal plasticity affects correlation between the size of dendritic spine and its postsynaptic density","volume":"9","author":"Borczyk","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1083\/jcb.201612042","article-title":"Phosphoinositide-dependent enrichment of actin monomers in dendritic spines regulates synapse development and plasticity","volume":"216","author":"Lei","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1756-6606-3-10","article-title":"Inhibition of AMPA receptor trafficking at hippocampal synapses by -amyloid oligomers: The mitochondrial contribution","volume":"3","author":"Rui","year":"2010","journal-title":"Mol. Brain"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.neuroscience.2014.05.046","article-title":"Extracellular proteolysis of reelin by tissue plasminogen activator following synaptic potentiation","volume":"274","author":"Trotter","year":"2014","journal-title":"Neuroscience"},{"key":"ref_98","first-page":"4","article-title":"Structural plasticity of hippocampal mossy fiber synapses as revealed by high-pressure freezing","volume":"53","author":"Zhao","year":"2012","journal-title":"J. Comp. Neurol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0896-6273(03)00206-X","article-title":"Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo","volume":"38","author":"Fukazawa","year":"2003","journal-title":"Neuron"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1038\/nature06416","article-title":"Locally dynamic synaptic learning rules in pyramidal neuron dendrites","volume":"450","author":"Harvey","year":"2007","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1038\/nn736","article-title":"Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons","volume":"4","author":"Matsuzaki","year":"2001","journal-title":"Nat. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"11388","DOI":"10.1073\/pnas.0802978105","article-title":"Delivery of AMPA receptors to perisynaptic sites precedes the full expression of long-term potentiation","volume":"105","author":"Yang","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/0006-8993(92)90767-4","article-title":"Long-term potentiation is associated with increased [3H]AMPA binding in rat hippocampus","volume":"573","author":"Tocco","year":"1992","journal-title":"Brain Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1046\/j.1471-4159.1998.70062434.x","article-title":"High- and low-affinity \u03b1-[3H] amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) binding sites. Represent immature and mature forms of AMPA receptors and are composed of differentially glycosylated subunits","volume":"70","author":"Standley","year":"1998","journal-title":"J. Neurochem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3389\/fnana.2019.00100","article-title":"Developmental changes of glutamate and GABA receptor densities in Wistar rats","volume":"13","author":"Behuet","year":"2019","journal-title":"Front. Neuroanat."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0006-8993(96)01468-0","article-title":"Sialic acid residues indirectly modulate the binding properties of AMPA-type glutamate receptors","volume":"753","author":"Hoffman","year":"1997","journal-title":"Brain Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.neuint.2011.08.014","article-title":"In vitro neuropharmacological evaluation of penitrem-induced tremorgenic syndromes: Importance of the GABAergic system","volume":"59","author":"Fonnum","year":"2011","journal-title":"Neurochem. Int."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1476-5381.1995.tb15876.x","article-title":"Subcellular localization and molecular pharmacology of distinct populations of [3H]-AMPA binding sites in rat hippocampus","volume":"115","author":"Henley","year":"1995","journal-title":"Br. J. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1111\/adb.12624","article-title":"Inhibition of alpha7 nicotinic receptors in the ventral hippocampus selectively attenuates reinstatement of morphine-conditioned place preference and associated changes in AMPA receptor binding","volume":"24","author":"Wright","year":"2019","journal-title":"Addict. Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"134488","DOI":"10.1016\/j.neulet.2019.134488","article-title":"Electrophysiological characterization of a novel AMPA receptor potentiator, TAK-137, in rat hippocampal neurons","volume":"712","author":"Suzuki","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3389\/fphar.2019.00105","article-title":"Bin The impact and mechanism of a novel allosteric AMPA receptor modulator LCX001 on protection against respiratory depression in rodents","volume":"10","author":"Dai","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/s41386-018-0213-7","article-title":"TAK-137, an AMPA-R potentiator with little agonistic effect, has a wide therapeutic window","volume":"44","author":"Kunugi","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Szepesi, Z., Bijata, M., Ruszczycki, B., Kaczmarek, L., and Wlodarczyk, J. (2013). Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063314"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.conb.2017.05.016","article-title":"Regulation of postsynaptic signaling in structural synaptic plasticity","volume":"45","author":"Fu","year":"2017","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.neuron.2008.01.013","article-title":"The subspine organization of actin fibers regulates the structure and plasticity of dendritic spines","volume":"57","author":"Honkura","year":"2008","journal-title":"Neuron"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.pneurobio.2011.04.011","article-title":"Control of synapse development and plasticity by Rho GTPase regulatory proteins","volume":"94","author":"Tolias","year":"2011","journal-title":"Prog. Neurobiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0896-6273(89)90039-1","article-title":"Cycling of actin assembly in synaptosomes and neurotransmitter release","volume":"3","author":"Bernstein","year":"1989","journal-title":"Neuron"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1093\/cercor\/bhu081","article-title":"ADF\/Cofilin controls synaptic actin dynamics and regulates synaptic vesicle mobilization and exocytosis","volume":"25","author":"Wolf","year":"2015","journal-title":"Cereb. Cortex"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Pelucchi, S., Stringhi, R., and Marcello, E. (2020). Dendritic spines in Alzheimer\u2019s disease: How the actin cytoskeleton contributes to synaptic failure. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030908"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e045764","DOI":"10.1002\/alz.045764","article-title":"Elucidating emerging therapeutics: P75 receptor modulation reverts tauopathy associated alterations in synapse-relevant gene expression signatures","volume":"16","author":"Losada","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00401-018-1880-5","article-title":"MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways","volume":"136","author":"Li","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e12791","DOI":"10.1111\/acel.12791","article-title":"Impaired AMPA signaling and cytoskeletal alterations induce early synaptic dysfunction in a mouse model of Alzheimer\u2019s disease","volume":"17","author":"Prieto","year":"2018","journal-title":"Aging Cell"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/5\/1174\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:59:37Z","timestamp":1760162377000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/5\/1174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,12]]},"references-count":122,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["cells10051174"],"URL":"https:\/\/doi.org\/10.3390\/cells10051174","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,12]]}}}