TAK-653 Reverses Core Depressive Symptoms in Chronic Stress-Induced Monkey Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Experimental Procedures
2.3. Measurement of Blood Cortisol and Inflammatory Cytokines
2.4. Behavioral Tests
2.5. TAK-653 Administration
2.6. Statistical Analysis
3. Results
3.1. Effective Modeling of MDD in Monkeys
3.2. TAK-653 Demonstrates Promising Antidepressant Effects
3.3. Fluctuation of Inflammatory Cytokines Concentration Provides Hints for Mechanism of Action
4. Discussion
4.1. The CUMS Paradigm Is Effective in Modeling MDD in Monkeys
4.2. The Effect of TAK-653 as an Antidepressant
4.3. Potential Mechanism of Antidepressant Effects
4.4. Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
MDD | Major Depressive Disorder |
AMPAR | α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors |
NMDAR | N-methyl-D-aspartate receptor |
BDNF | Brain-derived neurotrophic factor |
NHP | Non-human primate |
HPA | Hypothalamic-pituitary-adrenal |
CUMS | Chronic unpredictable mild stress |
AAT | The Attempt for Apple Test |
HIT | The Human Intruder Test |
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Stressor | Definition |
---|---|
Fasting | Food was withheld for a continuous duration of 24 h, commencing at 7:00 a.m. and concluding at 7:00 a.m. the next day. |
No water | Water access was deliberately limited for a continuous 12 h interval, precisely from 7:00 a.m. to 7:00 p.m., within a rigorously controlled experimental framework. |
Noise | A sound-emitting apparatus was installed inside the experimental unit to produce continuous noise over a 12 h interval, precisely from 7:00 p.m. to 7:00 a.m. the next morning. |
Stroboscope | A strobe light was installed one meter ahead of the monkey cages and activated to emit flashes at a frequency of 5 Hz continuously for a 12 h period. |
Inescapable foot shocks | Electrodes were firmly attached to the plantar surfaces of the monkeys’ feet to administer electrical stimulation. Each stimulus involved a current intensity between 1.0 and 1.25 mA, delivered for a duration of 3 to 5 s, followed by a 10 s pause before the next stimulus. This sequence was systematically repeated three to four times. |
Audiovisual stimulation | This presentation delivers a serious and detailed audiovisual depiction of the innate behavioral traits of large carnivores and raptors, encompassing actions such as roaring, running, and the pursuit and attack of prey. |
Spatial restriction | The adjustable lever inside the cage was set to restrict the monkey’s range of movement, allowing just enough room for the monkey to turn around. |
Behavior | Definition |
---|---|
Freezing | Remaining completely still in the same posture for a duration exceeding two seconds. |
Skin scratching | Repetitive motion of the fingers or toes moving across the fur. |
Yawning | Open mouth and yawn. |
Displaying signs of fear | The act of baring one’s canines, accompanied by widened eyes and an open mouth, serves as a deliberate display intended to intimidate others. |
Retreating to the bottom of the cage | A swift withdrawal to the base of the cage, ensuring that no fewer than three limbs maintain contact with the cage floor. |
Slow movements | Displaying at least three successive slow steps. |
Shaking the cage | Firmly grasp the cage and shake it with force. |
Swaying | Maintains an upright posture while swiftly oscillating from side to side. |
Grooming | Grooming hair or skin. |
Lip smacking | Swift and silent lip smacking. |
Behavior | Definition |
---|---|
Huddling posture | The position in which the head is situated between the shoulders and held lower than them while the individual is awake. |
Locomotion | Moving and walking in the cage |
Stereotypical behaviors | A consistent and recurring behavioral pattern that manifests no fewer than three times within a short timeframe. |
Environmental responses | Responses to novel environment, including activities such as exploration and feeding. |
Climbing | Climbing to the side walls or the top of the cage. |
Self-grooming | Self-grooming |
Ball play | Engaging in play with a ball that is suspended outside the confines of the cage. |
Observing | Gazing beyond the confines of the cage to examine the surrounding environment. |
Sitting | Remaining still, either seated or reclining at the base of the cage. |
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Li, L.; Zhang, Z.; Liu, X.; Zhou, M.; Wen, S.; Dai, J. TAK-653 Reverses Core Depressive Symptoms in Chronic Stress-Induced Monkey Model. Biomedicines 2025, 13, 1389. https://doi.org/10.3390/biomedicines13061389
Li L, Zhang Z, Liu X, Zhou M, Wen S, Dai J. TAK-653 Reverses Core Depressive Symptoms in Chronic Stress-Induced Monkey Model. Biomedicines. 2025; 13(6):1389. https://doi.org/10.3390/biomedicines13061389
Chicago/Turabian StyleLi, Ling, Zhiting Zhang, Xinhe Liu, Mengni Zhou, Shenglin Wen, and Ji Dai. 2025. "TAK-653 Reverses Core Depressive Symptoms in Chronic Stress-Induced Monkey Model" Biomedicines 13, no. 6: 1389. https://doi.org/10.3390/biomedicines13061389
APA StyleLi, L., Zhang, Z., Liu, X., Zhou, M., Wen, S., & Dai, J. (2025). TAK-653 Reverses Core Depressive Symptoms in Chronic Stress-Induced Monkey Model. Biomedicines, 13(6), 1389. https://doi.org/10.3390/biomedicines13061389