{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:45:08Z","timestamp":1793508308217,"version":"4.5.0"},"reference-count":118,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common neurodegenerative disorder worldwide. Mitochondrial dysfunction is thought to be an early event in the onset and progression of AD; however, the precise underlying mechanisms remain unclear. In this study, we investigated mitochondrial proteins involved in organelle dynamics, morphology and energy production in the medial prefrontal cortex (mPFC) and hippocampus (HIPP) of young (1\u223c2 months), adult (4\u223c5 months) and aged (9\u223c10, 12\u223c18 months) APP\/PS1 mice. We observed increased levels of mitochondrial fission protein, Drp1, and decreased levels of ATP synthase subunit, ATP5A, leading to abnormal mitochondrial morphology, increased oxidative stress, glial activation, apoptosis, and altered neuronal morphology as early as 4\u223c5 months of age in APP\/PS1 mice. Electrophysiological recordings revealed abnormal miniature excitatory postsynaptic current in the mPFC together with a minor connectivity change between the mPFC and HIPP, correlating with social deficits. These results suggest that abnormal mitochondrial dynamics, which worsen with disease progression, could be a biomarker of early-stage AD. Therapeutic interventions that improve mitochondrial function thus represent a promising approach for slowing the progression or delaying the onset of AD.<\/jats:p>","DOI":"10.3389\/fnagi.2021.748388","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T14:23:02Z","timestamp":1639146182000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Mitochondrial Deficits With Neural and Social Damage in Early-Stage Alzheimer\u2019s Disease Model Mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Afzal","family":"Misrani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidra","family":"Tabassum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwei","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaiya","family":"Tabassum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxiang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeel","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangmao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.bbadis.2016.11.005","article-title":"Nrf2 signaling pathway: Pivotal roles in inflammation.","volume":"1863","author":"Ahmed","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2020.566615","article-title":"Early-Occurring Dendritic Spines Alterations in Mouse Models of Alzheimer\u2019s Disease Inform on Primary Causes of Neurodegeneration.","volume":"12","author":"Ammassari-Teule","year":"2020","journal-title":"Front. Synaptic. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.freeradbiomed.2008.04.038","article-title":"Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury.","volume":"45","author":"Ansari","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"5099","DOI":"10.1523\/JNEUROSCI.2385-16.2017","article-title":"Inhibition of Drp1 Ameliorates Synaptic Depression, Abeta Deposition, and Cognitive Impairment in an Alzheimer\u2019s Disease Model.","volume":"37","author":"Baek","year":"2017","journal-title":"J. Neurosci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1080\/00207454.2020.1713776","article-title":"3-Nitrotyrosine: a versatile oxidative stress biomarker for major neurodegenerative diseases.","volume":"130","author":"Bandookwala","year":"2020","journal-title":"Int. J. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.nbd.2015.10.011","article-title":"Mitochondrial fusion\/fission dynamics in neurodegeneration and neuronal plasticity.","volume":"90","author":"Bertholet","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.1093\/cercor\/bhs239","article-title":"Dendritic morphology of pyramidal neurons in the chimpanzee neocortex: regional specializations and comparison to humans.","volume":"23","author":"Bianchi","year":"2013","journal-title":"Cereb Cortex"},{"key":"B8","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s13311-014-0324-8","article-title":"Targeting the prodromal stage of Alzheimer\u2019s disease: bioenergetic and mitochondrial opportunities.","volume":"12","author":"Caldwell","year":"2015","journal-title":"Neurotherapeutics"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16074-2","article-title":"Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer\u2019s disease.","volume":"11","author":"Calvo-Rodriguez","year":"2020","journal-title":"Nat. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/7854_2015_413","article-title":"Recognizing Others: Rodent\u2019s Social Memories.","volume":"30","author":"Camats Perna","year":"2017","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"6492","DOI":"10.1093\/hmg\/ddv358","article-title":"Mitochondrial ATP synthase activity is impaired by suppressed O-GlcNAcylation in Alzheimer\u2019s disease.","volume":"24","author":"Cha","year":"2015","journal-title":"Hum. Mole. Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.medengphy.2011.10.005","article-title":"Brain connectivity of patients with Alzheimer\u2019s disease by coherence and cross mutual information of electroencephalograms during photic stimulation.","volume":"35","author":"Chan","year":"2013","journal-title":"Med. Eng. Phys."},{"key":"B13","doi-asserted-by":"publisher","first-page":"R169","DOI":"10.1093\/hmg\/ddp326","article-title":"Mitochondrial dynamics\u2013fusion, fission, movement, and mitophagy\u2013in neurodegenerative diseases.","volume":"18","author":"Chen","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1083\/jcb.200211046","article-title":"Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development.","volume":"160","author":"Chen","year":"2003","journal-title":"J. Cell Biol."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00434-7","article-title":"Enhancing GABAergic signaling ameliorates aberrant gamma oscillations of olfactory bulb in AD mouse models.","volume":"16","author":"Chen","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.20142","article-title":"APP modulates KCC2 expression and function in hippocampal GABAergic inhibition.","volume":"2017","author":"Chen","year":"2017","journal-title":"Elife"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3791\/59310","article-title":"Evaluation of Hemisphere Lateralization with Bilateral Local Field Potential Recording in Secondary Motor Cortex of Mice.","volume":"149","author":"Chen","year":"2019","journal-title":"J. Vis. Exp"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00213","article-title":"Noradrenaline Increases mEPSC Frequency in Pyramidal Cells in Layer II of Rat Barrel Cortex via Calcium Release From Presynaptic Stores.","volume":"12","author":"Choy","year":"2018","journal-title":"Front. Cell Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"15927","DOI":"10.1073\/pnas.0407043101","article-title":"OPA1 requires mitofusin 1 to promote mitochondrial fusion.","volume":"101","author":"Cipolat","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"B20","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41586-021-03489-0","article-title":"Meningeal lymphatics affect microglia responses and anti-Abeta immunotherapy.","volume":"593","author":"Da Mesquita","year":"2021","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nn.2709","article-title":"Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer\u2019s disease.","volume":"14","author":"D\u2019amelio","year":"2011","journal-title":"Nat. Neurosci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1038\/nrm2275","article-title":"Functions and dysfunctions of mitochondrial dynamics.","volume":"8","author":"Detmer","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B23","doi-asserted-by":"publisher","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":"B24","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/nrn.2017.170","article-title":"Mitochondria at the neuronal presynapse in health and disease.","volume":"19","author":"Devine","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1089\/ars.2011.4277","article-title":"Synaptic mitochondrial pathology in Alzheimer\u2019s disease.","volume":"16","author":"Du","year":"2012","journal-title":"Antioxid Redox Signal"},{"key":"B26","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/35094565","article-title":"Dynamic predictions: oscillations and synchrony in top-down processing.","volume":"2","author":"Engel","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000016604","article-title":"Evaluation of hippocampal volume and serum brain-derived neurotrophic factor as potential diagnostic markers of conversion from amnestic mild cognitive impairment to Alzheimer disease: A STROBE-compliant article.","volume":"98","author":"Fang","year":"2019","journal-title":"Medicine"},{"key":"B28","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1016\/j.physbeh.2011.05.023","article-title":"Anomalies in social behaviors and exploratory activities in an APPswe\/PS1 mouse model of Alzheimer\u2019s disease.","volume":"104","author":"Filali","year":"2011","journal-title":"Physiol. Behav."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/srep32656","article-title":"Inhibition of Drp1 mitochondrial translocation provides neural protection in dopaminergic system in a Parkinson\u2019s disease model induced by MPTP.","volume":"2016","author":"Filichia","year":"2016","journal-title":"Sci. Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/nature20156","article-title":"Correcting mitochondrial fusion by manipulating mitofusin conformations.","volume":"540","author":"Franco","year":"2016","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.neuron.2017.11.028","article-title":"Alzheimer\u2019s Disease: From Firing Instability to Homeostasis Network Collapse.","volume":"97","author":"Frere","year":"2018","journal-title":"Neuron"},{"key":"B32","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/S1474-4422(17)30159-X","article-title":"Strategic roadmap for an early diagnosis of Alzheimer\u2019s disease based on biomarkers.","volume":"16","author":"Frisoni","year":"2017","journal-title":"Lancet Neurol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"16129","DOI":"10.1523\/JNEUROSCI.2323-12.2012","article-title":"Targeting astrocytes ameliorates neurologic changes in a mouse model of Alzheimer\u2019s disease.","volume":"32","author":"Furman","year":"2012","journal-title":"J. Neurosci."},{"key":"B34","doi-asserted-by":"publisher","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":"Garcia-Alloza","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.nbd.2018.09.020","article-title":"Cyclophilin D deficiency attenuates mitochondrial F1Fo ATP synthase dysfunction via OSCP in Alzheimer\u2019s disease.","volume":"121","author":"Gauba","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009764","article-title":"Synaptic plasticity in the hippocampus of a APP\/PS1 mouse model of Alzheimer\u2019s disease is impaired in old but not young mice.","volume":"5","author":"Gengler","year":"2010","journal-title":"PLoS One"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1007\/s10571-020-00790-w","article-title":"Silencing the Cytoskeleton Protein Iba1 (Ionized Calcium Binding Adapter Protein 1) Interferes with BV2 Microglia Functioning.","volume":"40","author":"Gheorghe","year":"2020","journal-title":"Cell Mol. Neurobiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1016\/j.bbadis.2014.09.014","article-title":"Region-specific metabolic alterations in the brain of the APP\/PS1 transgenic mice of Alzheimer\u2019s disease.","volume":"1842","author":"Gonzalez-Dominguez","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"B39","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1093\/brain\/124.4.739","article-title":"Altered brain functional connectivity and impaired short-term memory in Alzheimer\u2019s disease.","volume":"124","author":"Grady","year":"2001","journal-title":"Brain"},{"key":"B40","doi-asserted-by":"publisher","first-page":"17102","DOI":"10.1523\/JNEUROSCI.4623-10.2010","article-title":"More is less: a disinhibited prefrontal cortex impairs cognitive flexibility.","volume":"30","author":"Gruber","year":"2010","journal-title":"J. Neurosci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1196\/annals.1379.003","article-title":"Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer\u2019s disease.","volume":"1097","author":"Grutzendler","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1038\/nature01276","article-title":"Long-term dendritic spine stability in the adult cortex.","volume":"420","author":"Grutzendler","year":"2002","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.1016\/j.neurobiolaging.2014.03.026","article-title":"Neuronal driven pre-plaque inflammation in a transgenic rat model of Alzheimer\u2019s disease.","volume":"35","author":"Hanzel","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1016\/j.neurobiolaging.2007.12.005","article-title":"Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice.","volume":"30","author":"Hauptmann","year":"2009","journal-title":"Neurobiol. Aging"},{"key":"B45","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease.","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease.","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.2337\/db14-0758","article-title":"Drp1-mediated mitochondrial abnormalities link to synaptic injury in diabetes model.","volume":"64","author":"Huang","year":"2015","journal-title":"Diabetes"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008310","article-title":"Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer\u2019s disease.","volume":"4","author":"Iijima-Ando","year":"2009","journal-title":"PLoS One"},{"key":"B49","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1093\/hmg\/ddh019","article-title":"Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase.","volume":"13","author":"Jankowsky","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"B50","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/s1389-0344(01)00067-3","article-title":"Co-expression of multiple transgenes in mouse CNS: a comparison of strategies.","volume":"17","author":"Jankowsky","year":"2001","journal-title":"Biomol. Eng."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1038\/s41593-019-0486-0","article-title":"Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration.","volume":"22","author":"Joshi","year":"2019","journal-title":"Nat. Neurosci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"4881","DOI":"10.1093\/hmg\/ddw312","article-title":"Reduced dynamin-related protein 1 protects against phosphorylated Tau-induced mitochondrial dysfunction and synaptic damage in Alzheimer\u2019s disease.","volume":"25","author":"Kandimalla","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"B53","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/hmg\/ddx381","article-title":"Hippocampal phosphorylated tau induced cognitive decline, dendritic spine loss and mitochondrial abnormalities in a mouse model of Alzheimer\u2019s disease.","volume":"27","author":"Kandimalla","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"B54","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.neuroimage.2018.12.049","article-title":"Brain networks for engaging oneself in positive-social emotion regulation.","volume":"189","author":"Koush","year":"2019","journal-title":"Neuroimage"},{"key":"B55","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1126\/science.1115035","article-title":"Caspases 3 and 7: key mediators of mitochondrial events of apoptosis.","volume":"311","author":"Lakhani","year":"2006","journal-title":"Science"},{"key":"B56","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/nature20555","article-title":"Multiple dynamin family members collaborate to drive mitochondrial division.","volume":"540","author":"Lee","year":"2016","journal-title":"Nature"},{"key":"B57","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.cell.2004.11.003","article-title":"The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses.","volume":"119","author":"Li","year":"2004","journal-title":"Cell"},{"key":"B59","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1093\/hmg\/ddr139","article-title":"Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer\u2019s disease: implications for neuronal damage.","volume":"20","author":"Manczak","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"B60","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/hmg\/ddy335","article-title":"Mitochondrial division inhibitor 1 reduces dynamin-related protein 1 and mitochondrial fission activity.","volume":"28","author":"Manczak","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"B61","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.neuropharm.2013.08.005","article-title":"Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP\/PS1 mice, a model of Alzheimer\u2019s disease.","volume":"76","author":"Mcclean","year":"2014","journal-title":"Neuropharmacology"},{"key":"B62","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2021.617588","article-title":"Mitochondrial Dysfunction and Oxidative Stress in Alzheimer\u2019s Disease.","volume":"13","author":"Misrani","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.neuroscience.2018.12.042","article-title":"Functional Connectivity between Hippocampus and Lateral Septum is Affected in Very Young Alzheimer\u2019s Transgenic Mouse Model.","volume":"401","author":"Mondragon-Rodriguez","year":"2019","journal-title":"Neuroscience"},{"key":"B64","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/jmicro\/dfy125","article-title":"Scanning transmission electron microscopic analysis of nitrogen generated by 3, 3\u2019-diaminobenzidine-besed peroxidase reaction with resin ultrathin sections of rhinoceros parotid gland acinar cells.","volume":"68","author":"Moriguchi","year":"2019","journal-title":"Microscopy"},{"key":"B65","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/j.cmet.2014.07.024","article-title":"Amyloid-beta peptide induces mitochondrial dysfunction by inhibition of preprotein maturation.","volume":"20","author":"Mossmann","year":"2014","journal-title":"Cell Metab."},{"key":"B66","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1212\/01.wnl.0000338622.27876.0d","article-title":"Microglial activation and amyloid deposition in mild cognitive impairment: a PET study.","volume":"72","author":"Okello","year":"2009","journal-title":"Neurology"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1126\/science.aaf7003","article-title":"Ventral CA1 neurons store social memory.","volume":"353","author":"Okuyama","year":"2016","journal-title":"Science"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3390\/cells8090961","article-title":"Dynamics of Dynamin-Related Protein 1 in Alzheimer\u2019s Disease and Other Neurodegenerative Diseases.","volume":"2019","author":"Oliver","year":"2019","journal-title":"Cells"},{"key":"B69","doi-asserted-by":"publisher","first-page":"282","DOI":"10.21307\/ane-2017-027","article-title":"Age-dependent concomitant changes in synaptic dysfunction and GABAergic pathway in the APP\/PS1 mouse model.","volume":"76","author":"Oyelami","year":"2016","journal-title":"Acta Neurobiol. Exp."},{"key":"B70","article-title":"Amyloid-Beta interaction with mitochondria.","volume":"2011","author":"Pagani","year":"2011","journal-title":"Int. J. Alzheimers Dis."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1038\/npp.2017.56","article-title":"Bidirectional Control of Anxiety-Related Behaviors in Mice: Role of Inputs Arising from the Ventral Hippocampus to the Lateral Septum and Medial Prefrontal Cortex.","volume":"42","author":"Parfitt","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.44182","article-title":"Ventral hippocampal projections to the medial prefrontal cortex regulate social memory.","volume":"2019","author":"Phillips","year":"2019","journal-title":"Elife"},{"key":"B73","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1007\/s00401-018-1903-2","article-title":"Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer\u2019s disease.","volume":"136","author":"Pickett","year":"2018","journal-title":"Acta Neuropathol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"e1017","DOI":"10.1016\/j.neurobiolaging.2011.09.012","article-title":"Early development of social deficits in APP and APP-PS1 mice.","volume":"33","author":"Pietropaolo","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1016\/j.bbabio.2014.02.007","article-title":"Mitochondrial import and degradation of amyloid-beta peptide.","volume":"1837","author":"Pinho","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"B76","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","article-title":"Emerging roles of caspase-3 in apoptosis.","volume":"6","author":"Porter","year":"1999","journal-title":"Cell Death Differ"},{"key":"B77","doi-asserted-by":"crossref","first-page":"R764","DOI":"10.1016\/j.cub.2013.05.041","article-title":"Interplay of hippocampus and prefrontal cortex in memory.","volume":"23","author":"Preston","year":"2013","journal-title":"Curr. Biol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s12017-008-8044-z","article-title":"Mitochondrial medicine for aging and neurodegenerative diseases.","volume":"10","author":"Reddy","year":"2008","journal-title":"Neuromolecular. Med."},{"key":"B79","doi-asserted-by":"publisher","first-page":"147","DOI":"10.3233\/JAD-170051","article-title":"Mitochondria-Division Inhibitor 1 Protects Against Amyloid-beta induced Mitochondrial Fragmentation and Synaptic Damage in Alzheimer\u2019s Disease.","volume":"58","author":"Reddy","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"B80","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S0002-9440(10)62963-X","article-title":"Age-related loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL, PS1M146L, and APP751SL\/PS1M146L transgenic mice.","volume":"167","author":"Rutten","year":"2005","journal-title":"Am. J. Pathol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/s41583-020-0325-z","article-title":"Cellular senescence and Alzheimer disease: the egg and the chicken scenario.","volume":"21","author":"Saez-Atienzar","year":"2020","journal-title":"Nat. Rev. Neurosci."},{"key":"B82","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1159\/000329155","article-title":"Emotional working memory in Alzheimer\u2019s disease patients.","volume":"1","author":"Satler","year":"2011","journal-title":"Dement Geriatr. Cogn. Dis. Extra"},{"key":"B83","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1126\/science.1074069","article-title":"Alzheimer\u2019s disease is a synaptic failure.","volume":"298","author":"Selkoe","year":"2002","journal-title":"Science"},{"key":"B84","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/nrn3156","article-title":"Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration.","volume":"13","author":"Sheng","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.94","article-title":"Dynamin-related protein 1 is required for normal mitochondrial bioenergetic and synaptic function in CA1 hippocampal neurons.","volume":"6","author":"Shields","year":"2015","journal-title":"Cell Death Dis."},{"key":"B86","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.tins.2009.08.002","article-title":"Molecular dissection of reactive astrogliosis and glial scar formation.","volume":"32","author":"Sofroniew","year":"2009","journal-title":"Trends Neurosci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/nature14445","article-title":"Hippocampal-prefrontal input supports spatial encoding in working memory.","volume":"522","author":"Spellman","year":"2015","journal-title":"Nature"},{"key":"B88","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/s41556-018-0124-1","article-title":"The multifaceted contributions of mitochondria to cellular metabolism.","volume":"20","author":"Spinelli","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.cortex.2010.12.002","article-title":"Working memory, attention, and executive function in Alzheimer\u2019s disease and frontotemporal dementia.","volume":"48","author":"Stopford","year":"2012","journal-title":"Cortex"},{"key":"B90","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41593-018-0080-x","article-title":"Imbalance between firing homeostasis and synaptic plasticity drives early-phase Alzheimer\u2019s disease.","volume":"21","author":"Styr","year":"2018","journal-title":"Nat. Neurosci."},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.100894","article-title":"Ventral Hippocampal-Prefrontal Interaction Affects Social Behavior via Parvalbumin Positive Neurons in the Medial Prefrontal Cortex.","volume":"23","author":"Sun","year":"2020","journal-title":"iScience"},{"key":"B92","doi-asserted-by":"publisher","first-page":"69","DOI":"10.4161\/bioa.1.2.15469","article-title":"To branch or not to branch: How PSD-95 regulates dendrites and spines.","volume":"1","author":"Sweet","year":"2011","journal-title":"Bioarchitecture"},{"key":"B93","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/bs.pmbts.2016.12.017","article-title":"Mitochondria, Cybrids, Aging, and Alzheimer\u2019s Disease.","volume":"146","author":"Swerdlow","year":"2017","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41114-3","article-title":"Jujuboside A prevents sleep loss-induced disturbance of hippocampal neuronal excitability and memory impairment in young APP\/PS1 mice.","volume":"9","author":"Tabassum","year":"2019","journal-title":"Sci. Rep."},{"key":"B95","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/s0896-6273(00)81248-9","article-title":"Mitochondrial involvement in post-tetanic potentiation of synaptic transmission.","volume":"18","author":"Tang","year":"1997","journal-title":"Neuron"},{"key":"B96","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1111\/j.1750-3639.2009.00266.x","article-title":"Mitochondrial ATP-synthase in the entorhinal cortex is a target of oxidative stress at stages I\/II of Alzheimer\u2019s disease pathology.","volume":"20","author":"Terni","year":"2010","journal-title":"Brain Pathol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/1098-1063(2000)10:4<411::AID-HIPO7>3.0.CO;2-A","article-title":"Hippocampo-prefrontal cortex pathway: anatomical and electrophysiological characteristics.","volume":"10","author":"Thierry","year":"2000","journal-title":"Hippocampus"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.3233\/jad-161088","article-title":"Oxidative Stress, Synaptic Dysfunction, and Alzheimer\u2019s Disease.","volume":"57","author":"Tonnies","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"B99","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1038\/nn1335","article-title":"Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches.","volume":"7","author":"Tsai","year":"2004","journal-title":"Nat. Neurosci."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1038\/s41593-020-00737-w","article-title":"Acute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life.","volume":"23","author":"Uhlmann","year":"2020","journal-title":"Nat. Neurosci."},{"key":"B101","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41583-019-0240-3","article-title":"Amyloid-beta-independent regulators of tau pathology in Alzheimer disease.","volume":"21","author":"Van Der Kant","year":"2020","journal-title":"Nat. Rev. Neurosci."},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2017.06.050","article-title":"Inflammation and mitochondrial dysfunction: A vicious circle in neurodegenerative disorders?","volume":"710","author":"Van Horssen","year":"2019","journal-title":"Neurosci. Lett."},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11915","article-title":"Early synaptic deficits in the APP\/PS1 mouse model of Alzheimer\u2019s disease involve neuronal adenosine A2A receptors.","volume":"7","author":"Viana Da Silva","year":"2016","journal-title":"Nat. Commun."},{"key":"B104","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nrneurol.2018.9","article-title":"Imaging tau and amyloid-beta proteinopathies in Alzheimer disease and other conditions.","volume":"14","author":"Villemagne","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"2339","DOI":"10.1016\/j.celrep.2018.10.103","article-title":"The Mitochondrial Apoptotic Effectors BAX\/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1beta Activation.","volume":"25","author":"Vince","year":"2018","journal-title":"Cell Rep."},{"key":"B106","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.neuroimage.2005.12.033","article-title":"Changes in hippocampal connectivity in the early stages of Alzheimer\u2019s disease: evidence from resting state fMRI.","volume":"31","author":"Wang","year":"2006","journal-title":"Neuroimage"},{"key":"B107","doi-asserted-by":"publisher","first-page":"4118","DOI":"10.1093\/hmg\/ddx299","article-title":"Inhibition of mitochondrial fragmentation protects against Alzheimer\u2019s disease in rodent model.","volume":"26","author":"Wang","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-020-00376-6","article-title":"Mitochondria dysfunction in the pathogenesis of Alzheimer\u2019s disease: recent advances.","volume":"15","author":"Wang","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"B109","doi-asserted-by":"publisher","first-page":"9090","DOI":"10.1523\/JNEUROSCI.1357-09.2009","article-title":"Impaired balance of mitochondrial fission and fusion in Alzheimer\u2019s disease.","volume":"29","author":"Wang","year":"2009","journal-title":"J. Neurosci."},{"key":"B110","doi-asserted-by":"publisher","first-page":"15801","DOI":"10.1523\/JNEUROSCI.1569-10.2010","article-title":"Task-dependent changes in short-term memory in the prefrontal cortex.","volume":"30","author":"Warden","year":"2010","journal-title":"J. Neurosci."},{"key":"B111","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/nn.2476","article-title":"Amyloid beta from axons and dendrites reduces local spine number and plasticity.","volume":"13","author":"Wei","year":"2010","journal-title":"Nat. Neurosci."},{"key":"B112","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1038\/nrm3013","article-title":"Mitochondrial fusion and fission in cell life and death.","volume":"11","author":"Westermann","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4606752","article-title":"Ligustilide Ameliorates Memory Deficiency in APP\/PS1 Transgenic Mice via Restoring Mitochondrial Dysfunction.","volume":"2018","author":"Xu","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00326","article-title":"Altered Directed Functional Connectivity of the Hippocampus in Mild Cognitive Impairment and Alzheimer\u2019s Disease: A Resting-State fMRI Study.","volume":"11","author":"Xue","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"B115","doi-asserted-by":"publisher","first-page":"14670","DOI":"10.1073\/pnas.0903563106","article-title":"Mitochondrial bioenergetic deficit precedes Alzheimer\u2019s pathology in female mouse model of Alzheimer\u2019s disease.","volume":"106","author":"Yao","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"B116","doi-asserted-by":"publisher","first-page":"S221","DOI":"10.3233\/JAD-2012-120709","article-title":"Donepezil effects on hippocampal and prefrontal functional connectivity in Alzheimer\u2019s disease: preliminary report.","author":"Zaidel","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2020.585513","article-title":"Optimized Golgi-Cox Staining Validated in the Hippocampus of Spared Nerve Injury Mouse Model.","volume":"14","author":"Zhang","year":"2020","journal-title":"Front. Neuroanat."},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2019.00399","article-title":"Brain Connectivity Based Prediction of Alzheimer\u2019s Disease in Patients With Mild Cognitive Impairment Based on Multi-Modal Images.","volume":"13","author":"Zheng","year":"2019","journal-title":"Front. Hum. Neurosci."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2021.748388\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T14:23:11Z","timestamp":1639146191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2021.748388\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,10]]},"references-count":118,"alternative-id":["10.3389\/fnagi.2021.748388"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2021.748388","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,10]]},"article-number":"748388"}}