Effects of early-life stress on peripheral and central mitochondria in male mice across ages

S R Ruigrok; K Yim; T L Emmerzaal; B Geenen; N Stöberl; J L den Blaauwen; M R Abbink; A J Kiliaan; E M van Schothorst; T Kozicz; A Korosi

doi:10.1016/j.psyneuen.2021.105346

Effects of early-life stress on peripheral and central mitochondria in male mice across ages

Psychoneuroendocrinology. 2021 Oct:132:105346. doi: 10.1016/j.psyneuen.2021.105346. Epub 2021 Jun 29.

Authors

S R Ruigrok¹, K Yim¹, T L Emmerzaal², B Geenen³, N Stöberl¹, J L den Blaauwen¹, M R Abbink¹, A J Kiliaan³, E M van Schothorst⁴, T Kozicz², A Korosi⁵

Affiliations

¹ Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
² Department of Medical Imaging - Anatomy, Radboud University Medical Center, Donders Institute for Brain Cognition and Behaviour, Nijmegen, The Netherlands; Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
³ Department of Medical Imaging - Anatomy, Radboud University Medical Center, Donders Institute for Brain Cognition and Behaviour, Nijmegen, The Netherlands.
⁴ Human and Animal Physiology, Wageningen University, 6700AH Wageningen, The Netherlands.
⁵ Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: a.korosi@uva.nl.

PMID: 34274734
DOI: 10.1016/j.psyneuen.2021.105346

Abstract

Exposure to early-life stress (ES) increases the vulnerability to develop metabolic diseases as well as cognitive dysfunction, but the specific biological underpinning of the ES-induced programming is unknown. Metabolic and cognitive disorders are often comorbid, suggesting possible converging underlying pathways. Mitochondrial dysfunction is implicated in both metabolic diseases and cognitive dysfunction and chronic stress impairs mitochondrial functioning. However, if and how mitochondria are impacted by ES and whether they are implicated in the ES-induced programming remains to be determined. ES was applied by providing mice with limited nesting and bedding material from postnatal day (P)2-P9, and metabolic parameters, cognitive functions and multiple aspects of mitochondria biology (i.e. mitochondrial electron transport chain (ETC) complex activity, mitochondrial DNA copy number, expression of genes relevant for mitochondrial function, and the antioxidant capacity) were studied in muscle, hypothalamus and hippocampus at P9 and late adulthood (10-12 months of age). We show that ES altered bodyweight (gain), adiposity and glucose levels at P9, but not in late adulthood. At this age, however, ES exposure led to cognitive impairments. ES affected peripheral and central mitochondria in an age-dependent manner. At P9, both muscle and hypothalamic ETC activity were affected by ES, while in hippocampus, ES altered the expression of genes involved in fission and antioxidant defence. In adulthood, alterations in ETC complex activity were observed in the hypothalamus specifically, whereas in muscle and hippocampus ES affected the expression of genes involved in mitophagy and fission, respectively. Our study demonstrates that ES affects peripheral and central mitochondria biology throughout life, thereby uncovering a converging mechanism that might contribute to the ES-induced vulnerability for both metabolic diseases and cognitive dysfunction, which could serve as a novel target for intervention.

Keywords: Cognition; Early-life stress; Metabolism; Mitochondria.

MeSH terms

Age Factors
Animals
Male
Mice
Mitochondria* / physiology
Stress, Psychological* / physiopathology