Evidence map›Paper›PMID 40944731›Full record

ArticlePsychopharmacology2026

Chemogenetic activation of the medial prefrontal cortex alleviates the impaired extinction of fear memory through the increase in the binding of EGR1 and TET1 in an animal model of PTSD.

Sho Fujita, Manabu Fuchikami, Satoshi Fujita, Tatsuhiro Miyagi, Satoshi Okada, Jun Omura, Shigeru Morinobu

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Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Sho FujitaDepartment of Psychiatry and Neuroscience, Division of Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-Ku, Kasumi 1-2-3, Hiroshima, Japan.
Manabu FuchikamiDepartment of Psychiatry and Neuroscience, Division of Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-Ku, Kasumi 1-2-3, Hiroshima, Japan. mf547@hiroshima-u.ac.jp.ORCID http://orcid.org/0000-0002-7759-6813
Satoshi FujitaDepartment of Psychiatry and Neuroscience, Division of Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-Ku, Kasumi 1-2-3, Hiroshima, Japan.
Tatsuhiro MiyagiDepartment of Psychiatry and Neuroscience, Division of Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-Ku, Kasumi 1-2-3, Hiroshima, Japan.
Satoshi OkadaDepartment of Psychiatry and Neuroscience, Division of Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-Ku, Kasumi 1-2-3, Hiroshima, Japan.
Jun OmuraDepartment of Psychiatry and Neuroscience, Division of Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-Ku, Kasumi 1-2-3, Hiroshima, Japan.
Shigeru MorinobuDepartment of Psychology, School of Faculty of Health and Wellness Sciences, Hiroshima International University, Kure, Japan.

Funding

Japan Society for the Promotion of Science JP25K19060
6 · The paper itself

Abstract

rationaleImpaired extinction of fear memory (EFM) is one of the principal symptoms of posttraumatic stress disorder (PTSD). We recently reported that chemogenetic activation (CA) of the infralimbic cortex (ILC) during extinction training did not reduce fear instantly but rather facilitated later extinction retrieval in a single prolonged stress (SPS) rats, an animal model of PTSD.

objectiveWe examined the mechanism by which CA alleviates the impaired EFM in SPS rats.

methodsWe measured protein levels of Early Growth Response 1 (EGR1) and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) by western blotting, levels of binding of these two proteins by co-immunoprecipitation and western blotting, and levels of 5-hydroxymethylcytosine (5hmC), an indicator of DNA demethylation, by ELISA. Bobcat339 was used as a selective TET inhibitor, and EFM was evaluated using extinction training and extinction testing following contextual fear conditioning.

resultsCA of the ILC increased the binding of EGR1 and TET1 and increased the 5hmc level in the prefrontal cortex. Administration of Bobcat339 inhibited the 5hmc increase and the alleviation of impaired EFM by the CA of the ILC in SPS rats. The extinction training was indispensable for the increased binding of EGR1 and TET1 and the alleviation of impaired EFM in response to the CA of the ILC.

conclusionOur results suggest that CA alleviates the impaired EFM via the increase in EGR1-TET1 binding in SPS rats. Pharmacotherapy promoting DNA demethylation through the activation of the TET1 cascade may be pivotal in the treatment of PTSD.

Indexed as

DNA-Binding ProteinsEarly Growth Response Protein 1Extinction, PsychologicalFearMemoryPrefrontal CortexProto-Oncogene ProteinsStress Disorders, Post-Traumatic5-MethylcytosineAnimalsChemogeneticsDioxygenasesDisease Models, AnimalMaleRatsRats, Sprague-Dawley5-MethylcytosineDioxygenasesDNA-Binding ProteinsEarly Growth Response Protein 1Egr1 protein, ratProto-Oncogene ProteinsTET1 protein, ratChemogenetic activationDNA methylationEarly growth response 1 (EGR1)Fear memory extinctionMedial prefrontal cortexPost-traumatic stress disorder (PTSD)Ten-eleven translocation methylcytosine dioxygenase 1 (TET1)

Identifiers

PMID40944731

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.