Regional and cell type-specific activation of the unfolded protein response after kainate injection in mice.
| Title: | Regional and cell type-specific activation of the unfolded protein response after kainate injection in mice. |
|---|---|
| Authors: | Nguyen LH; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Nguyen LD; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Dao DX; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Hattori T; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Kashihara, Nara, Japan.; Ishii H; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Takarada-Iemata M; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Hori O; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan. Electronic address: osamuh3@staff.kanazawa-u.ac.jp. |
| Source: | Neurochemistry international [Neurochem Int] 2025 Dec; Vol. 191, pp. 106071. Date of Electronic Publication: 2025 Oct 09. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Pergamon Press Country of Publication: England NLM ID: 8006959 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9754 (Electronic) Linking ISSN: 01970186 NLM ISO Abbreviation: Neurochem Int Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford [Elmsford, N. Y.] Pergamon Press. |
| MeSH Terms: | Unfolded Protein Response*/drug effects ; Unfolded Protein Response*/physiology ; Kainic Acid*/administration & dosage ; Kainic Acid*/toxicity ; Kainic Acid*/pharmacology ; Hippocampus*/drug effects ; Hippocampus*/metabolism ; Neurons*/drug effects ; Neurons*/metabolism; Endoplasmic Reticulum Stress/drug effects ; Animals ; Mice ; Mice, Transgenic ; Male ; Mice, Inbred C57BL |
| Abstract: | The unfolded protein response (UPR) is activated under different neuropathological conditions, such as brain ischemia, epilepsy, and neurodegeneration. We previously reported that a UPR transducer, activating transcription factor 6 (ATF6), and its downstream molecular chaperones in the endoplasmic reticulum (ER) have neuroprotective properties against excitotoxicity. In this study, we examined the temporal and spatial changes in the UPR activation after administration of an excitotoxic reagent, kainate (KA), into mice. RT-qPCR revealed enhanced expression of UPR genes, with peaks either on day 1 or day 3 after intrahippocampal KA injection. The status of the UPR was analyzed using ER stress-activated indicator (ERAI)-transgenic mice, in which the spliced form of XBP-1, downstream of the IRE1 branch of the UPR, can be monitored. ERAI-derived GFP signals were strongly observed in CA3 neurons and moderately observed in dentate gyrus neurons, but not in CA1 neurons, after KA injection. A small portion of the activated astrocytes was also positive for ERAI signals. Further studies revealed that ERAI signals were observed in both the soma and dendrites of neurons in regions with enhanced neuronal activity and resistance to KA toxicity. These results suggest that the UPR may be associated with the neuronal activity and survival after KA injection.; (Copyright © 2025 Elsevier Ltd. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare no conflicts of interest. |
| Contributed Indexing: | Keywords: Excitotoxity; Proteostasis; Unfolded protein response |
| Substance Nomenclature: | SIV03811UC (Kainic Acid) |
| Entry Date(s): | Date Created: 20251009 Date Completed: 20251205 Latest Revision: 20260428 |
| Update Code: | 20260428 |
| DOI: | 10.1016/j.neuint.2025.106071 |
| PMID: | 41067391 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't