{"doi":"10.1101/642207","title":"Unique axon-to-soma signaling pathways mediate dendritic spine loss and hyper-excitability post-axotomy","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Axon damage may cause axon regeneration, retrograde synapse loss, and hyper-excitability, all of which affect recovery following acquired brain injury. While axon regeneration is studied extensively, less is known about signaling mediating retrograde synapse loss and hyper-excitability, especially in long projection pyramidal neurons. To investigate intrinsic injury signaling within neurons, we use an\n                  <jats:italic>in vitro</jats:italic>\n                  microfluidic platform that models dendritic spine loss and delayed hyper-excitability following remote axon injury. Our data show that sodium influx and reversal of sodium calcium exchangers (NCXs) at the site of axotomy, mediate dendritic spine loss following axotomy. In contrast, sodium influx and NCX reversal alone are insufficient to cause retrograde hyper-excitability. We found that calcium release from axonal ER is critical for the induction of hyper-excitability and inhibition loss. These data suggest that synapse loss and hyper-excitability are uncoupled responses following axon injury. Further, axonal ER may play a critical and underappreciated role in mediating retrograde hyper-excitability within the CNS.\n                </jats:p>","journal":null,"year":null,"id":661837,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":533447,"name":"Anne Marion Taylor","orcid":"0000-0003-0998-087X","position":1,"is_corresponding":false},{"id":596647,"name":"Tharkika Nagendran","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Unique axon-to-soma signaling pathways mediate dendritic spine loss and hyper-excitability post-axotomy","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Axon damage may cause axon regeneration, retrograde synapse loss, and hyper-excitability, all of which affect recovery following acquired brain injury. While axon regeneration is studied extensively, less is known about signaling mediating retrograde synapse loss and hyper-excitability, especially in long projection pyramidal neurons. To investigate intrinsic injury signaling within neurons, we use an\n                  <jats:italic>in vitro</jats:italic>\n                  microfluidic platform that models dendritic spine loss and delayed hyper-excitability following remote axon injury. Our data show that sodium influx and reversal of sodium calcium exchangers (NCXs) at the site of axotomy, mediate dendritic spine loss following axotomy. In contrast, sodium influx and NCX reversal alone are insufficient to cause retrograde hyper-excitability. We found that calcium release from axonal ER is critical for the induction of hyper-excitability and inhibition loss. These data suggest that synapse loss and hyper-excitability are uncoupled responses following axon injury. Further, axonal ER may play a critical and underappreciated role in mediating retrograde hyper-excitability within the CNS.\n                </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31607869","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"5P30NS045892-03","title":"Core--Expression localization"},{"funder_name":"National Institutes of Health","grant_id":"1R41NS108895-01","title":"A user-friendly microfluidic chip for anti-epileptogenic drug screening"},{"funder_name":"National Institutes of Health","grant_id":"2P30CA014195-31","title":"Senior Leadership"},{"funder_name":"National Institutes of Health","grant_id":"3R42MH097377-04S1","title":"A user-friendly scalable microfluidic platform for enhanced neuron-cell culture"},{"funder_name":"National Institutes of Health","grant_id":"5P30NS045892-18","title":"UNC Neuroscience Center Research Cores"}],"total_grants":5,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"CC BY","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2019/05/20/642207.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/642207","host_type":"publisher"},{"url":"https://doi.org/10.1101/642207","host_type":""},{"url":"https://www.frontiersin.org/articles/10.3389/fncel.2019.00431/pdf","host_type":""},{"url":"https://doi.org/10.3389/fncel.2019.00431","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/31607869","host_type":""},{"url":"http://dx.doi.org/10.3389/fncel.2019.00431","host_type":""},{"url":"https://doaj.org/article/877bd88baf6f4f3c85e81d3d7d559242","host_type":""},{"url":"https://dx.doi.org/10.1101/642207","host_type":""},{"url":"https://dx.doi.org/10.3389/fncel.2019.00431","host_type":""},{"url":"http://dx.doi.org/10.1101/642207","host_type":""}],"fields_of_study":["0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["retrograde signaling","axotomy","axon-to-soma","injury model","Neurosciences. Biological psychiatry. Neuropsychiatry","hyper-excitability","dendritic spine loss","RC321-571","Neuroscience"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T11:45:08.394338Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}