The Mitochondrion as Potential Interface in Early-Life Stress Brain Programming.

Anke Hoffmann,Dietmar Spengler

doi:10.3389/fnbeh.2018.00306

Abstract

Mitochondria play a central role in cellular energy-generating processes and are master regulators of cell life. They provide the energy necessary to reinstate and sustain homeostasis in response to stress, and to launch energy intensive adaptation programs to ensure an organism’s survival and future well-being. By this means, mitochondria are particularly apt to mediate brain programming by early-life stress (ELS) and to serve at the same time as subcellular substrate in the programming process. With a focus on mitochondria’s integrated role in metabolism, steroidogenesis and oxidative stress, we review current findings on altered mitochondrial function in the brain, the placenta and peripheral blood cells following ELS-dependent programming in rodents and recent insights from humans exposed to early life adversity (ELA). Concluding, we propose a role of the mitochondrion as subcellular intersection point connecting ELS, brain programming and mental well-being, and a role as a potential site for therapeutic interventions in individuals exposed to severe ELS.

Highlights

Life experiences can cause lasting changes in brain structure and function
Maternal exposure to adversity during pregnancy impacts the quality of fetal growth and development and enhances the risk for disturbed HPA-axis regulation in the offspring, a known risk factor for various psychiatric disorders such as schizophrenia or major depression (O’Donnell and Meaney, 2017)
Estrogen receptors translocate to the mitochondrion, increase adenosine triphosphate (ATP) levels in primary neuronal cultures, maximize mitochondrial respiratory rate in neurons and glia, and protect against ETC inhibitors (Nilsen and Diaz Brinton, 2003). These results suggest that estrogens coordinate the response of mitochondrial enzymes and improve mitochondrial bioenergetics in the brain

Summary

Introduction

Life experiences can cause lasting changes in brain structure and function. This process is often referred to as developmental programming (Gluckman and Hanson, 2004) and evolves from developmental plasticity. Over the past 20 years, increasing evidence indicates a role of mitochondrial steroidogenesis in ELS-dependent brain programming extending from intrauterine to perinatal life and beyond, and by modulation of maternal stress responsivity. In light of mitochondrion’s role in the mediation and regulation of early stress responses, we focus on concrete examples supporting the role of mitochondrial function and ROS production in ELS-dependent programming of rodent brains.

Results

Conclusion