Abstract
BackgroundEarly-life stress in the form of maternal separation can be associated with alterations in offspring neurodevelopment and brain functioning. Here, we aimed to investigate the potential impact of prolonged maternal separation on proteomic profiling of prefrontal cortex, hippocampus and cerebellum of juvenile and young adult rats. A special attention was devoted to proteins involved in the process of cell death and redox state maintenance.MethodsLong-Evans pups were separated from their mothers for 3 h daily over the first 3 weeks of life (during days 2–21 of age). Brain tissue samples collected from juvenile (22-day-old) and young adult (90-day-old) rats were used for label-free quantitative (LFQ) proteomic analysis. In parallel, selected oxidative stress markers and apoptosis-related proteins were assessed biochemically and by Western blot, respectively.ResultsIn total, 5526 proteins were detected in our proteomic analysis of rat brain tissue. Approximately one tenth of them (586 proteins) represented those involved in cell death processes or regulation of oxidative stress balance. Prolonged maternal separation caused changes in less than half of these proteins (271). The observed alterations in protein expression levels were age-, sex- and brain region-dependent. Interestingly, the proteins detected by mass spectrometry that are known to be involved in the maintenance of redox state were not markedly altered. Accordingly, we did not observe any significant differences between selected oxidative stress markers, such as the levels of hydrogen peroxide, reduced glutathione, protein carbonylation and lipid peroxidation in brain samples from rats that underwent maternal separation and from the corresponding controls. On the other hand, a number of changes were found in cell death-associated proteins, mainly in those involved in the apoptotic and autophagic pathways. However, there were no detectable alterations in the levels of cleaved products of caspases or Bcl-2 family members. Taken together, these data indicate that the apoptotic and autophagic cell death pathways were not activated by maternal separation either in adolescent or young adult rats.ConclusionProlonged maternal separation can distinctly modulate expression profiles of proteins associated with cell death pathways in prefrontal cortex, hippocampus and cerebellum of juvenile rats and the consequences of early-life stress may last into adulthood and likely participate in variations in stress reactivity.
Highlights
Early-life stress in the form of maternal separation can be associated with alterations in offspring neurodevelopment and brain functioning
Prolonged maternal separation may have a great impact on cell death-related protein expression profiling in different brain regions of both juvenile and adult rats
Because a 3-week regimen of maternal separation apparently did not elicit oxidative stress and cleavage of some caspases and other members of the apoptotic machinery, we assume that if apoptosis or autophagic cell death was triggered by this type of early postnatal stress in the course of the first three weeks, the activation of these processes would be only transitory and suppressed by adaptive responses
Summary
Early-life stress in the form of maternal separation can be associated with alterations in offspring neurodevelopment and brain functioning. A wide range of consequences of exposure to ELS was identified, involving morphological, neuroendocrine, behavioral, metabolic and epigenetic alterations in the offspring’s development. These changes can underlie the increased susceptibility to infectious, metabolic, cardiovascular and psychiatric diseases in later life [1]. The large individual variability and disease susceptibility arise from the interaction between biological (e.g., sex, age of assessment, predisposing genetic polymorphisms in genes and epigenetic signature in genes) and environmental factors (e.g., nature of stressors, timing and duration of exposure during development, severity and cumulative exposure effects, maternal care and health, nutrition) [3, 4]
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