We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Behavioral and transcriptional effects of repeated electroconvulsive seizures in the neonatal MK-801-treated rat model of schizophrenia.
- Authors
Lee, Jeonghoon; Huh, Seonghoo; Park, Kyungtaek; Kang, Nuree; Yu, Hyun Sook; Park, Hong Geun; Kim, Yong Sik; Kang, Ung Gu; Won, Sungho; Kim, Se Hyun
- Abstract
Rationale: Electroconvulsive therapy (ECT) is an effective treatment modality for schizophrenia. However, its antipsychotic-like mechanism remains unclear. Objectives: To gain insight into the antipsychotic-like actions of ECT, this study investigated how repeated treatments of electroconvulsive seizure (ECS), an animal model for ECT, affect the behavioral and transcriptomic profile of a neurodevelopmental animal model of schizophrenia. Methods: Two injections of MK-801 or saline were administered to rats on postnatal day 7 (PN7), and either repeated ECS treatments (E10X) or sham shock was conducted daily from PN50 to PN59. Ultimately, the rats were divided into vehicle/sham (V/S), MK-801/sham (M/S), vehicle/ECS (V/E), and MK-801/ECS (M/E) groups. On PN59, prepulse inhibition and locomotor activity were tested. Prefrontal cortex transcriptomes were analyzed with mRNA sequencing and network and pathway analyses, and quantitative real-time polymerase chain reaction (qPCR) analyses were subsequently conducted. Results: Prepulse inhibition deficit was induced by MK-801 and normalized by E10X. In M/S vs. M/E model, Egr1, Mmp9, and S100a6 were identified as center genes, and interleukin-17 (IL-17), nuclear factor kappa B (NF-κB), and tumor necrosis factor (TNF) signaling pathways were identified as the three most relevant pathways. In the V/E vs. V/S model, mitophagy, NF-κB, and receptor for advanced glycation end products (RAGE) pathways were identified. qPCR analyses demonstrated that Igfbp6, Btf3, Cox6a2, and H2az1 were downregulated in M/S and upregulated in M/E. Conclusions: E10X reverses the behavioral changes induced by MK-801 and produces transcriptional changes in inflammatory, insulin, and mitophagy pathways, which provide mechanistic insight into the antipsychotic-like mechanism of ECT.
- Subjects
RECEPTOR for advanced glycation end products (RAGE); NF-kappa B; ADVANCED glycation end-products; TUMOR necrosis factors; NEURAL inhibition; ELECTROCONVULSIVE therapy
- Publication
Psychopharmacology, 2024, Vol 241, Issue 4, p817
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-023-06511-7