Intergenerational trauma transmission is associated with brain metabotranscriptome remodeling and mitochondrial...

Area of Science:

• Neuroscience
• Psychiatry
• Developmental Biology

Background:

• Intergenerational trauma elevates the risk for depression and psychiatric disorders.
• The mechanisms of intergenerational trauma transmission, whether via in-utero neurodevelopmental disruptions or early-life interactions, remain unclear.

Purpose of the Study:

• To investigate the impact of prenatal trauma exposure on offspring behavior and brain function in mice.
• To elucidate the contributing factors to intergenerational trauma transmission, specifically in-utero versus early-life environment.
• To explore potential therapeutic interventions for trauma-induced behavioral deficits.

Main Methods:

• Mice were exposed to trauma during pregnancy.
• Offspring behavior was assessed for social deficits and depressive-like behaviors.
• Brain metabotranscriptome analysis was performed on neonates and adults.
• Pharmacological intervention with acetyl-L-carnitine (ALCAR) was administered.

Main Results:

• Prenatal trauma exposure induced social deficits and depressive-like behaviors in mouse offspring.
• Both biologically related and adopted pups raised by traumatized mothers showed similar deficits, suggesting a two-hit model (in-utero and early-life environment).
• Elevated 2-hydroxyglutaric acid levels indicated mitochondrial dysfunction and epigenetic alterations.
• ALCAR supplementation provided long-lasting protection against these trauma-induced behavioral changes.

Conclusions:

• Intergenerational trauma involves both prenatal neurodevelopmental disruptions and early-life environmental factors.
• Mitochondrial dysfunction and epigenetic modifications are key mechanisms underlying these effects.
• Early ALCAR supplementation is a promising therapeutic strategy for mitigating the long-term consequences of intergenerational trauma.