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Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Mature brain-derived neurotrophic factor has long been known to as an epigenetic regulator. It is excessively secreted after status epilepticus, leading to a variety of permanent structural and functional changes in the brain. While its precursor forms proBDNF regulates nerve development, neural transmission and cognitive function, it is not fully known whether the expression of proBDNF is changed\n                      <jats:italic>in vivo<\/jats:italic>\n                      or how it influences neuronal signaling and function ultimately leading to spatial cognitive impairments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we investigated changes in proBDNF levels in the hippocampus of the pentylenetetrazole (pentylenetetrazole)-induced epileptic rat model. Functional blocking of proBDNF singling and its related pathway in the hippocampal regions was conducted to explore the potential mechanisms. Meanwhile, local field potentials were recorded in the hippocampal CA3-CA1 pathway and the directionality of neural information flow (NIF) between two regions was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that seizures were induced by PTZ-treated rats, which exhibited excessive proBDNF expression in the hippocampus only after undergoing behavioral training. Intra-hippocampal infusions of anti-proBDNF antibody into the CA1 but not the CA3 region could mitigate the PTZ-induced memory consolidation deficits and we confirmed the involvement of p75\n                      <jats:sup>NTR<\/jats:sup>\n                      rather than TrkB signaling. The excessive proBDNF could act on both presynaptic and postsynaptic sites through p75\n                      <jats:sup>NTR<\/jats:sup>\n                      signaling to exaggerate neural activity of putative fast-spiking interneurons. This was evidenced by increased spontaneous excitatory postsynaptic current frequency and amplitude, and further corroborated by action potential-independent miniature EPSC (mEPSC) recordings, which revealed concurrent increases in both mEPSC frequency and amplitude specifically in the epilepsy group. Importantly, this over-expression of proBDNF disrupted phase synchronization and directional coupling strength at the CA3 to CA1 synapses. However, blocking proBDNF or inactivation of the p75\n                      <jats:sup>NTR<\/jats:sup>\n                      signaling could effectively enhance the phase-locked value and neural information flow at the gamma and high-frequency oscillations, and significantly alleviate the PTZ-induced impairments in memory processing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings are consistent with the hypothesis and provide the first direct evidence that the over-activation of proBDNF signaling represents a potential mechanism involved in neural dysfunction and NIF disruption leading to memory impairments in kindled animals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1881525","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:11:11Z","timestamp":1784095871000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pentylenetetrazole kindling impairs place recognition memory associated with suppressing proBDNF-mediated neural information flows at the hippocampal CA3-CA1 synapses"],"prefix":"10.3389","volume":"17","author":[{"given":"Wei","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Emergency, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine","place":["Guiyang, China"]},{"name":"Department of Neonatology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanyong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Langfang Normal University","place":["Langfang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Jinan Geriatric\/Rehabilitation Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chundan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Langfang Normal University","place":["Langfang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"An","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine","place":["Guiyang, China"]},{"name":"Department of Neonatology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine","place":["Guiyang, China"]},{"name":"Department of Neurology, Jinan Geriatric\/Rehabilitation Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.conb.2021.05.005","article-title":"From synapse to network: models of information storage and retrieval in neural circuits","volume":"70","author":"Aljadeff","year":"2021","journal-title":"Curr. 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