1. Academic Validation
  2. Exogenous IGF-1 alleviates depression-like behavior and hippocampal mitochondrial dysfunction in high-fat diet mice

Exogenous IGF-1 alleviates depression-like behavior and hippocampal mitochondrial dysfunction in high-fat diet mice

  • Physiol Behav. 2021 Feb 1;229:113236. doi: 10.1016/j.physbeh.2020.113236.
Caixia Yang 1 Guanghong Sui 2 Dai Li 3 Lu Wang 3 Shishuang Zhang 3 Ping Lei 3 Zheng Chen 4 Feng Wang 5
Affiliations

Affiliations

  • 1 Department of Rehabilitation, Tianjin Anding Hospital, Tianjin 300074, China.
  • 2 Department of Child and Adolescent Psychology, Tianjin Anding Hospital, Tianjin 300074, China.
  • 3 Department of Psychology, Tianjin Anding Hospital, Tianjin 300074, China; Department of Geriatrics, Tianjin Medical University General Hospital; Tianjin Geriatrics Institute, Tianjin 300052, China.
  • 4 Department of Psychology, Tianjin Anding Hospital, Tianjin 300074, China. Electronic address: Zheng4365@126.com.
  • 5 Department of Psychology, Tianjin Anding Hospital, Tianjin 300074, China; Department of Geriatrics, Tianjin Medical University General Hospital; Tianjin Geriatrics Institute, Tianjin 300052, China. Electronic address: wangfeng0921@126.com.
Abstract

Background: Some evidence suggests that depression is more common in obese patients. This fact gives us a hint that obesity might be a promoter of depression, though a conclusion can not be drawn. The aim of the study was: (1) to confirm whether obesity induced by high-fat diet (HFD) promotes depression-like behaviors in mice, (2) to explore the protective role of insulin-like growth factor-1 (IGF-1) in such behavioral disorder of the Animals and (3) to reveal whether mitochondrial mechanism was involved in such protective effect of the reagent.

Methods: C57BL/6 J mice were fed with HFD to establish a model of obesity. Then, the Animals were separately or simultaneously treated with PEG-IGF-1, 666-15 (CREB blocker) and SR-18292 (PGC-1α blocker). After that, depression-like behaviors were assessed using sucrose preference test and tail suspension test. In hippocampus, respiratory control ratio, ATP generation and red/green fluorescence ratio were adopted to reveal mitochondrial function. Also in hippocampus, expressions of p-CREB and PGC-1α were measured using western blotting.

Results: HFD mice showed depression-like behaviors compared with control mice. Such diet also caused mitochondrial dysfunction and inhibition of CREB/PGC-1α signal pathway in hippocampus of these Animals. After PEG-IGF-1 intervention, all the abnormalities mentioned above can be partly reversed. After 666-15 or SR-18292 treatment, such protective effect of PEG-IGF-1 can be attenuated, and the mice suffered from the re-deterioration of behavioral and mitochondrial abnormalities in hippocampus.

Conclusion: IGF-1 alleviated depression-like behaviors and mitochondrial dysfunction through the activation of CREB/PGC-1α signal pathway in HFD mice.

Keywords

Depression; Insulin-like growth factor I; Mitochondrial dysfunction; Obesity; cAMP-response element binding protein.

Figures
Products
Inhibitors & Agonists
Other Products