Nuclear factor of activated T cells 4 in the prefrontal cortex is required for prophylactic actions of (R)-ketamine

• DOI: 10.1038/s41398-022-01803-6
• Publication Date: 2022-01-21T07:02:53Z
• Authors: Li Ma; Jiancheng Zhang; Yuko Fujita; Youge Qu; Jiajing Shan; Xiayun Wan; Xingming Wang; Tamaki Ishima; Kenta Kobayashi; Long Wang; Kenji Hashimoto
• Keywords: Lipopolysaccharides; Depression; T-Lymphocytes; Prefrontal Cortex; Neurosciences. Biological psychiatry. Neuropsychiatry; Article; Antidepressive Agents; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Ketamine; RC321-571

(R, S)-ketamine has prophylactic antidepressant-like effects in rodents; however, the precise molecular mechanisms underlying its action remain unknown. Using RNA-sequencing analysis, we searched novel target(s) that contribute to of (R)-ketamine, a more potent enantiomer S)-ketamine. Pretreatment with (R)-ketamine (10 mg/kg, 6 days before) significantly ameliorated body weight loss, splenomegaly, and increased immobility time forced swimming test lipopolysaccharide (LPS: 1.0 mg/kg)-treated mice. analysis prefrontal cortex (PFC) subsequent IPA (Ingenuity Pathway Analysis) revealed nuclear factor activated T cells 4 (NFATc4) signaling might sustained (R)-ketamine. Quantitative RT-PCR confirmed attenuated gene expression NFATc4 (Nfatc4, Cd4, Cd79b, H2-ab1, H2-aa) PFC LPS-treated Furthermore, pretreatment NFAT inhibitors (i.e., inhibitor cyclosporin A) showed Similar knockdown Nfatc4 by bilateral injection adeno-associated virus (AAV) into mPFC could elicit In conclusion, our data implicate pathway for inflammation-related depression.