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Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain

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Neurosteroids and early-life programming: An updated perspective.

Ying Sze¹, Paula J Brunton¹

¹Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, Scotland, UK.

Current Opinion in Endocrine and Metabolic Research

|December 23, 2022

Summary

Early-life stress impacts offspring by disrupting neurosteroids, increasing risks for mood disorders. Understanding neurosteroid function is key to addressing these stress-induced changes.

Keywords:

Allopregnanolone Anxiety GABA receptors HPA axis Mass spectrometry Sex differences THDOC

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Area of Science:

Neuroendocrinology
Developmental Neuroscience
Behavioral Neuroscience

Background:

Early-life stress (ELS) has profound, lasting effects on offspring, including mood disorders and hypothalamic-pituitary-adrenal (HPA) axis dysregulation.
Neurosteroids are critical modulators of neuronal excitability and stress response termination.
Reduced neurosteroidogenesis is linked to aberrant neuroendocrine and behavioral phenotypes in ELS rodents.

Purpose of the Study:

To review recent advances in understanding the interaction between neurosteroids and ELS outcomes.
To examine the role of neurosteroids during development and their long-term programming effects.
To highlight future research directions, including quantification, sex differences, and therapeutic potential.

Main Methods:

Literature review of recent scientific advances.
Focus on studies investigating neurosteroidogenesis and its impact on stress-related outcomes.
Analysis of research concerning perinatal and adult offspring exposed to ELS.

Main Results:

Disruptions in neurosteroid generation and action during development can lead to long-term programming of brain and behavior.
Reduced neurosteroidogenesis is a key factor in the neuroendocrine and behavioral abnormalities seen in adult ELS rodents.
Neurosteroids rapidly modulate neuronal activity and aid in stress response termination.

Conclusions:

Neurosteroids play a crucial role in mitigating the adverse effects of early-life stress.
Further research is needed to explore quantification methods, sex-specific effects, and the therapeutic potential of neurosteroids for ELS-related disorders.