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. 2023 Apr 17:10:1113570.
doi: 10.3389/fmolb.2023.1113570. eCollection 2023.

Porcine blood cell and brain tissue energy metabolism: Effects of "early life stress"

Franziska Münz  1   2 , Eva-Maria Wolfschmitt  1 , Fabian Zink  1 , Nadja Abele  1 , Melanie Hogg  1 , Andrea Hoffmann  1 , Michael Gröger  1 , Enrico Calzia  1 , Christiane Waller  3 , Peter Radermacher  1 , Tamara Merz  1   2
Affiliations

Porcine blood cell and brain tissue energy metabolism: Effects of "early life stress"

Franziska Münz et al. Front Mol Biosci. .

Abstract

Background: Early Life Stress (ELS) may exert long-lasting biological effects, e.g., on PBMC energy metabolism and mitochondrial respiration. Data on its effect on brain tissue mitochondrial respiration is scarce, and it is unclear whether blood cell mitochondrial activity mirrors that of brain tissue. This study investigated blood immune cell and brain tissue mitochondrial respiratory activity in a porcine ELS model. Methods: This prospective randomized, controlled, animal investigation comprised 12 German Large White swine of either sex, which were weaned at PND (postnatal day) 28-35 (control) or PND21 (ELS). At 20-24 weeks, animals were anesthetized, mechanically ventilated and surgically instrumented. We determined serum hormone, cytokine, and "brain injury marker" levels, superoxide anion (O2 •¯) formation and mitochondrial respiration in isolated immune cells and immediate post mortem frontal cortex brain tissue. Results: ELS animals presented with higher glucose levels, lower mean arterial pressure. Most determined serum factors did not differ. In male controls, TNFα and IL-10 levels were both higher than in female controls as well as, no matter the gender in ELS animals. MAP-2, GFAP, and NSE were also higher in male controls than in the other three groups. Neither PBMC routine respiration and brain tissue oxidative phosphorylation nor maximal electron transfer capacity in the uncoupled state (ETC) showed any difference between ELS and controls. There was no significant relation between brain tissue and PBMC, ETC, or brain tissue, ETC, and PBMC bioenergetic health index. Whole blood O2 •¯ concentrations and PBMC O2 •¯ production were comparable between groups. However, granulocyte O2 •¯ production after stimulation with E. coli was lower in the ELS group, and this effect was sex-specific: increased O2 •¯ production increased upon stimulation in all control animals, which was abolished in the female ELS swine. Conclusion: This study provides evidence that ELS i) may, gender-specifically, affect the immune response to general anesthesia as well as O2 •¯ radical production at sexual maturity, ii) has limited effects on brain and peripheral blood immune cell mitochondrial respiratory activity, and iii) mitochondrial respiratory activity of peripheral blood immune cells and brain tissue do not correlate.

Keywords: PBMC; electron spin resonance; granulocyte; high resolution respirometry; mitochondrial respiration; superoxide anion.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Serum cortisol, tumor necrosis factor (TNF, left panel) and interleukin-10 (IL-10, right panel) levels in the in the control (blue symbols) and Early Life Stress (ELS; red symbols) groups separated for male (“m”, solid squares) and female (“f”, open circles) swine. Note that male control animals showed markedly higher cytokine concentrations than females, while there was no sex-related difference in the ELS swine.
FIGURE 2
FIGURE 2
Serum microtubule-associated protein 2 (MAP-2) (upper left panel), glial fibrillary acidic protein (GFAP) (upper right panel), neuron-specific enolase (NSE) (lower left panel) and protein S100β (lower right panel) in the control and Early Life Stress (ELS) groups for the control (blue symbols) and Early Life Stress (ELS; red symbols) groups separated for male (“m”, solid squares) and female (“f”, open circles) swine. Note that male control animals showed markedly higher “serum brain injury marker” concentrations than females, while there was no sex-related difference in the ELS swine.
FIGURE 3
FIGURE 3
Mitochondrial respiration (left column: oxidative phosphorylation (OxPhos)/physiological coupling state (Routine); right column: maximum electron transport capacity of the respiratory chain in the uncoupled state) in immediate post mortem brain specimen (JO 2 [pmol/s/mgtissue]) (upper panel) as well as in isolated peripheral blood mononuclear cells (PBMC, middle panel) (JO 2 [pmol/s/106 cells]) and granulocytes (lower panel) JO 2 [pmol/s/106 cells(]) for the control (blue symbols) and Early Life Stress (ELS; red symbols) groups in male (solid squares) and female (open circles) swine. Note that as expected, ETC., in PBMC was markedly higher than in granulocytes.
FIGURE 4
FIGURE 4
Whole blood superoxide anion (O2 •¯) concentration in the control (blue symbols) and Early Life Stress (ELS; red symbols) groups separated for male (“m”, solid squares) and female (“f”, open circles) swine (upper panel). Granulocyte superoxide anion (O2 •¯) production at baseline and after stimulation of phagocytosis with E. coli in control (blue symbols) and Early Life Stress (ELS; red symbols) animals separated for male (solid symboles) and female (open symboles) swine (lower panel). Each symbol refers to samples from an individual animal. Note that O2 •¯ release increased upon stimulation in all samples from male swine irrespective of the presence/absence of ELS, while this response was abolished in female animals with ELS.
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