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Upregulating TrkB\/C signaling could reduce Alzheimer's disease (AD)\u2010related degenerative signaling, memory loss, and synaptic dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      PTX\u2010BD10\u20102 (BD10\u20102), a small molecule TrkB\/C receptor partial agonist, was orally administered to aged London\/Swedish\u2010APP mutant mice (APP\n                      <jats:sup>L\/S<\/jats:sup>\n                      ) and wild\u2010type controls. Effects on memory and hippocampal long\u2010term potentiation (LTP) were assessed using electrophysiology, behavioral studies, immunoblotting, immunofluorescence staining, and RNA sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In APP\n                      <jats:sup>L\/S<\/jats:sup>\n                      mice, BD10\u20102 treatment improved memory and LTP deficits. This was accompanied by normalized phosphorylation of protein kinase B (Akt), calcium\u2010calmodulin\u2013dependent kinase II (CaMKII), and AMPA\u2010type glutamate receptors containing the subunit GluA1; enhanced activity\u2010dependent recruitment of synaptic proteins; and increased excitatory synapse number. BD10\u20102 also had potentially favorable effects on LTP\u2010dependent complement pathway and synaptic gene transcription.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      BD10\u20102 prevented APP\n                      <jats:sup>L\/S<\/jats:sup>\n                      \/A\u03b2\u2010associated memory and LTP deficits, reduced abnormalities in synapse\u2010related signaling and activity\u2010dependent transcription of synaptic genes, and bolstered transcriptional changes associated with microglial immune response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Small molecule modulation of tropomyosin related kinase B (TrkB) and C (TrkC) restores long\u2010term potentiation (LTP) and behavior in an Alzheimer's disease (AD) model.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Modulation of TrkB and TrkC regulates synaptic activity\u2010dependent transcription.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>TrkB and TrkC receptors are candidate targets for translational therapeutics.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Electrophysiology combined with transcriptomics elucidates synaptic restoration.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>LTP identifies neuron and microglia AD\u2010relevant human\u2010mouse co\u2010expression modules.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.13857","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T04:41:24Z","timestamp":1716439284000},"page":"4434-4460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A TrkB and TrkC partial agonist restores deficits in synaptic function and promotes activity\u2010dependent synaptic and microglial transcriptomic changes in a late\u2010stage Alzheimer's mouse model"],"prefix":"10.1002","volume":"20","author":[{"given":"Amira","family":"Latif\u2010Hernandez","sequence":"first","affiliation":[{"name":"Department of Neurology &amp; 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