1. Social support rescues acute stress-induced cognitive impairments by modulating ERK1/2 phosphorylation in adolescent mice.
- Author
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Kim JW, Ko MJ, Gonzales EL, Kang RJ, Kim DG, Kim Y, Seung H, Oh HA, Eun PH, and Shin CY
- Subjects
- Age Factors, Aminoacetonitrile administration & dosage, Aminoacetonitrile analogs & derivatives, Animals, Cognitive Dysfunction blood, Cognitive Dysfunction etiology, Corticosterone blood, Early Growth Response Protein 1 metabolism, MAP Kinase Signaling System drug effects, MAP Kinase Signaling System physiology, Male, Maze Learning physiology, Memory, Short-Term physiology, Mice, Mice, Inbred ICR, Mitogen-Activated Protein Kinase 1 antagonists & inhibitors, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 antagonists & inhibitors, Mitogen-Activated Protein Kinase 3 metabolism, Phosphorylation drug effects, Phosphorylation physiology, Prefrontal Cortex metabolism, Protease Inhibitors administration & dosage, Stress, Psychological blood, Stress, Psychological psychology, Transcriptional Activation drug effects, Up-Regulation drug effects, Animal Communication, Cognitive Dysfunction prevention & control, Social Behavior, Stress, Psychological complications
- Abstract
Social support can relieve stress-induced behavioural outcomes, although its underlying molecular mechanisms are not fully understood. Here, we evaluated whether social interactions can prevent the restraint stress (RS)-induced cognitive impairments in male adolescent mice by utilizing molecular, cellular, and behavioural approaches. Acute RS in adolescent ICR mice impaired the working memory in the Y-maze test and memory consolidation and retrieval in the novel-object-recognition test (NORT). In addition, RS increased the extracellular signal-regulated kinases 1/2 phosphorylation (p-ERK1/2) in the prefrontal cortex (PFC) and corticosterone levels in the plasma. Interestingly, these outcomes were normalized by the presence of a conspecific animal (social support) during RS. RS also significantly upregulated the expression levels of known stress-relevant genes such as Egr1, Crh, and Crhr1, which were normalized by social support. Systemic injection of SL327 (an inhibitor of MEK1/2 that also blocks its downstream signal ERK1/2) prior to RS rescued the working memory impairments and the increased p-ERK1/2 while normalizing the expression of Egr1. Our results suggest that social support can alleviate the RS-induced cognitive impairments partly by modulating ERK1/2 phosphorylation and gene transcription in the PFC, and provide novel insights into the molecular mechanisms of the stress-buffering effects of social support.
- Published
- 2018
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