{"doi":"10.1101/2023.08.31.555794","title":"Neuronal acid-sensing ion channel 1a regulates neuron-to-glioma synapses","abstract":"ABSTRACT Neuronal activity promotes high-grade glioma progression via secreted proteins and neuron-to-glioma synapses, and glioma cells boost neuronal activity to further reinforce the malignant cycle. Whereas strong evidence supports that the activity of neuron-to-glioma synapses accelerates tumor progression, the molecular mechanisms that modulate the formation and function of neuron-to-glioma synapses remain largely unknown. Our recent findings suggest that a proton (H + ) signaling pathway actively mediates neuron-to-glioma synaptic communications by activating neuronal acid-sensing ion channel 1a (Asic1a), a predominant H + receptor in the central nervous system (CNS). Supporting this idea, our preliminary data revealed that local acid puff on neurons in high-grade glioma-bearing brain slices induces postsynaptic currents of glioma cells. Stimulating Asic1a knockout (Asic1a -/- ) neurons results in lower AMPA receptor-dependent excitatory postsynaptic currents (EPSCs) in glioma cells than stimulating wild-type (WT) neurons. Moreover, glioma-bearing Asic1a -/- mice exhibited reduced tumor size and survived longer than the glioma-bearing WT mice. Finally, pharmacologically targeting brain Asic1a inhibited high-grade glioma progression. In conclusion, our findings suggest that the neuronal H + -Asic1a axis plays a key role in regulating the neuron-glioma synapse. The outcomes of this study will greatly expand our understanding of how this deadly tumor integrates into the neuronal microenvironment.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":393603,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1167671,"name":"Zhen Jin","orcid":"0000-0003-0540-5173","position":1,"is_corresponding":false},{"id":1168138,"name":"Qian Ge","orcid":null,"position":2,"is_corresponding":false},{"id":282268,"name":"Yuan Pan","orcid":"0000-0002-9465-8289","position":3,"is_corresponding":false},{"id":792317,"name":"Jianyang Du","orcid":"0000-0002-4342-0975","position":4,"is_corresponding":false},{"id":1167670,"name":"Kyung Ah Park","orcid":"0000-0003-4368-8813","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T01:19:05.913428Z","pmid":"37693494","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":[]}