Social support rescues acute stress-induced cognitive impairments by modulating ERK1/2 phosphorylation in adolescent...

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• Social support is known to mitigate stress, but its molecular underpinnings remain unclear.
• Adolescent stress can lead to cognitive impairments, impacting memory and executive functions.
• Understanding the neurobiological basis of social buffering is crucial for developing interventions.

Purpose of the Study:

• To investigate if social interactions can prevent restraint stress (RS)-induced cognitive impairments in adolescent mice.
• To elucidate the molecular and cellular mechanisms underlying the stress-buffering effects of social support.
• To explore the role of extracellular signal-regulated kinases 1/2 (ERK1/2) signaling in stress-induced cognitive deficits.

Main Methods:

• Utilized molecular, cellular, and behavioral approaches in male adolescent mice.
• Assessed cognitive functions using Y-maze and novel-object-recognition tests (NORT).
• Measured plasma corticosterone levels, prefrontal cortex (PFC) p-ERK1/2, and stress-related gene expression (Egr1, Crh, Crhr1).
• Administered SL327, a MEK1/2 inhibitor, to block ERK1/2 signaling.

Main Results:

• Acute restraint stress (RS) impaired working memory and recognition memory in adolescent mice.
• RS increased plasma corticosterone and PFC p-ERK1/2 levels, alongside upregulated stress-related genes.
• Social support during RS normalized cognitive performance, corticosterone levels, and gene expression.
• MEK1/2 inhibition with SL327 before RS rescued cognitive impairments and normalized p-ERK1/2 and Egr1 expression.

Conclusions:

• Social support alleviates RS-induced cognitive impairments in adolescent mice.
• The stress-buffering effect of social support involves modulation of ERK1/2 phosphorylation and gene transcription in the PFC.
• This study provides novel insights into the molecular mechanisms of social support in mitigating stress.