دورية أكاديمية
Microglial activation in the medial prefrontal cortex after remote fear recall participates in the regulation of auditory fear extinction.
| العنوان: | Microglial activation in the medial prefrontal cortex after remote fear recall participates in the regulation of auditory fear extinction. |
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| المؤلفون: | Zou GJ; Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan, 410013, China; School of Basic Medicine, Yiyang Medical College, Yiyang, Hunan, 413000, China., Chen ZR; Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan, 410013, China; Hunan University of Chinese Medicine, Changsha, Hunan, 410219, China., Wang XQ; Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Neurodegenerative Diseases, Changsha Medical University, Changsha, Hunan, 410219, China., Cui YH; Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan, 410013, China., Li F; Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan, 410013, China., Li CQ; Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan, 410013, China., Wang LF; Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Neurodegenerative Diseases, Changsha Medical University, Changsha, Hunan, 410219, China. Electronic address: laifawang@126.com., Huang FL; School of Basic Medicine, Yiyang Medical College, Yiyang, Hunan, 413000, China. Electronic address: hflscience@126.com. |
| المصدر: | European journal of pharmacology [Eur J Pharmacol] 2024 Sep 05; Vol. 978, pp. 176759. Date of Electronic Publication: 2024 Jun 18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2005- : Amsterdam : Elsevier Science Original Publication: Amsterdam, North Holland Pub. Co. |
| مواضيع طبية MeSH: | Fear*/physiology , Fear*/psychology , Prefrontal Cortex*/metabolism , Prefrontal Cortex*/physiology , Microglia*/metabolism , Extinction, Psychological*/physiology , Mental Recall*/physiology , Mice, Inbred C57BL* , Kruppel-Like Factor 4*, Animals ; Male ; Mice ; Microfilament Proteins/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Disks Large Homolog 4 Protein/metabolism ; Acoustic Stimulation/adverse effects ; Signal Transduction |
| مستخلص: | Excessive or inappropriate fear responses can lead to anxiety-related disorders, such as post-traumatic stress disorder (PTSD). Studies have shown that microglial activation occurs after fear conditioning and that microglial inhibition impacts fear memory. However, the role of microglia in fear memory recall remains unclear. In this study, we investigated the activated profiles of microglia after the recall of remote-cued fear memory and the role of activated microglia in the extinction of remote-cued fear in adult male C57BL/6 mice. The results revealed that the expression of the microglia marker Iba1 increased in the medial prefrontal cortex (mPFC) at 10 min and 1 h following remote-cued fear recall, which was accompanied by amoeboid morphology. Inhibiting microglial activation through PLX3397 treatment before remote fear recall did not affect recall, reconsolidation, or regular extinction but facilitated recall-extinction and mitigated spontaneous recovery. Moreover, our results demonstrated reduced co-expression of Iba1 and postsynaptic density protein 95 (PSD95) in the mPFC, along with decreases in the p-PI3K/PI3K ratio, p-Akt/Akt ratio, and KLF4 expression after PLX3397 treatment. Our results suggest that microglial activation after remote fear recall impedes fear extinction through the pruning of synapses in the mPFC, accompanied by alterations in the expression of the PI3K/AKT/KLF4 pathway. This finding can help elucidate the mechanism involved in remote fear extinction, contributing to the theoretical foundation for the intervention and treatment of PTSD. Competing Interests: Declaration of competing interest The authors declare no conflict of interest. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Fear extinction; Microglia; PLX3397; Recall; Remote memory |
| المشرفين على المادة: | 0 (Kruppel-Like Factor 4) 0 (Klf4 protein, mouse) 0 (Microfilament Proteins) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) 0 (Disks Large Homolog 4 Protein) |
| تواريخ الأحداث: | Date Created: 20240620 Date Completed: 20240725 Latest Revision: 20240725 |
| رمز التحديث: | 20240726 |
| DOI: | 10.1016/j.ejphar.2024.176759 |
| PMID: | 38901527 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0712 |
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| DOI: | 10.1016/j.ejphar.2024.176759 |