Transcriptomic analysis reveals mitochondrial pathways associated with distinct adolescent behavioral phenotypes and...

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Adolescent brain development shows significant variability in cortical dynamics and behavior.
• Mitochondrial gene expression in the prefrontal cortex (PFC) is crucial for brain maturation and mental health.
• The impact of adolescent stress on PFC mitochondria and associated behaviors is not fully understood.

Purpose of the Study:

• To investigate changes in PFC mitochondria-related genes and respiratory capacity in adolescent rats with distinct behavioral phenotypes.
• To examine the effects of early adolescent stress on these mitochondrial features and behaviors.

Main Methods:

• Behavioral characterization of adolescent rats (anxiety, sociability, cognition) using standardized tests.
• Genome-wide transcriptional profiling to analyze mitochondria-related gene expression.
• High-resolution respirometry to assess mitochondrial respiratory chain capacity.

Main Results:

• Principal component analysis identified three distinct behavioral clusters: high-behavioral z-score (HBZ), low-behavioral z-score (LBZ), and stressed animals.
• Mitochondria-related genes, particularly those for oxidative phosphorylation, were down-regulated in LBZ and stressed animals.
• LBZ and stressed animals showed reduced PFC phosphorylation capacity and redox dysregulation, with specific genes (Ndufa10, Cox6a1) identified as central.
• Down-regulation of oxidative phosphorylation genes correlated positively with behavioral z-scores.

Conclusions:

• Distinct adolescent behavioral phenotypes are associated with specific alterations in PFC mitochondria.
• Early adolescent stress negatively impacts PFC mitochondria function, leading to reduced respiratory capacity and redox dysregulation.
• Mitochondrial dysfunction in the PFC may underlie behavioral variability and the consequences of adolescent stress.