Esketamine induces tripartite motif-containing protein 24 to improve cognitive dysfunction in Alzheimer's disease.
Yingbing Tu, Bin Xu
Neuroscience Letters June 21, 2024 DOI: 10.1016/j.neulet.2024.137836 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Triple transgenic Alzheimer's disease (3xTg-AD) mice |
| Intervention | Esketamine |
| Topics | Esketamine |
| Keywords | 3xtg-ad mice Alzheimer’s disease Pi3k/akt pathway Trim24 Alzheimer's disease ad Dementia Neurodegenerative disease Drug development Drug discovery Clinical trials Neuroscience brain research Neurology Neural science Brain studies |
| Citations | 3 |
| Key findings | Esketamine ameliorates cognitive deficits and reduces neuroinflammation in 3xTg-AD mice via TRIM24-mediated activation of the PI3K/AKT pathway. |
Abstract
Esketamine has been revealed to improve cognitive impairments under different conditions, while its function in Alzheimer's disease (AD) has not been well characterized. We expounded the effects and detailed mechanism of esketamine in triple transgenic AD (3xTg-AD) mice in the present study. The impaired spatial learning and memory retention of 3xTg-AD mice were ameliorated by esketamine, whereas tripartite motif-containing protein 24 (TRIM24) depletion reversed the ameliorative effects of esketamine in 3xTg-AD mice. Esketamine elevated the extent of PI3K and AKT phosphorylation in the hippocampus by promoting TRIM24 expression, and knockdown of TRIM24 impaired the PI3K/AKT pathway. AD-like mice had increased expression of pro-inflammatory molecules and elevated expression of GFAP and p-Tau. Esketamine reduced inflammation, but its therapeutic effect was reversed by TRIM24 knockdown. The PI3K/AKT pathway blockage exacerbated cognitive deficits and neuroinflammatory responses in mice. Thus, esketamine has the potential to improve the cognitive and memory functions of 3xTg-AD mice by repressing neuroinflammation by activating TRIM24 and the downstream PI3K/AKT pathway.
Comparable studies
Other preclinical and animal studies on esketamine, most cited first.
Citations in the library
Cited by 2
- Combinatorial targeting of NMDARs and 5-HT4Rs exerts beneficial effects in a mouse model of Alzheimer's disease. Alzheimer's Research & Therapy July 15, 2025
- Esketamine alleviates neuroinflammation and cognitive impairment in male 3xTg-AD mice by regulating the TAOK1/IL-17 axis. Canadian journal of physiology and pharmacology January 1, 2026
Cites 3
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- The therapeutic role of ketamine and esketamine in treating psychopathological domains of depression. Neuropharmacology November 1, 2022
- Esketamine alleviates postoperative depression-like behavior through anti-inflammatory actions in mouse prefrontal cortex. Journal of Affective Disorders April 1, 2022