A systematic review and multilevel meta-analysis of the prenatal and early life stress effects on rodent microglia, astrocyte, and oligodendrocyte density and morphology.

Exposure to stress during early development may lead to altered neurobiological functions, thus increasing the risk for psychiatric illnesses later in life. One potential mechanism associated with those outcomes is the disruption of glial density and morphology, despite results from rodent studies have been conflicting. To address that we performed a systematic review and meta-analysis of rodent studies that investigated the effects of prenatal stress (PNS) and early life stress (ELS) on microglia, astrocyte, and oligodendrocyte density and morphology within the offspring. Our meta-analysis demonstrates that animals exposed to PNS or ELS showed significant increase in microglia density, as well as decreased oligodendrocyte density. Moreover, ELS exposure induced an increase in microglia soma size. However, we were unable to identify significant effects on astrocytes. Meta-regression indicated that experimental stress protocol, sex, age, and type of tissue analyzed are important covariates that impact those results. Importantly, PNS microglia showed higher estimates in young animals, while the ELS effects were stronger in adult animals. This set of data reinforces that alterations in glial cells could play a role in stress-induced dysfunctions throughout development.

Effects of early life stress on brain cytokines: A systematic review and meta-analysis of rodent studies.

Exposure to early life stress (ELS) may lead to long-lasting neurobiological and behavioral impairments. Alterations in the immune system and neuroinflammatory state induced by ELS exposure are considered risk factors for developing psychiatric disorders. Here, we performed a systematic review and meta-analysis of rodent studies investigating the short and long-term effects of ELS exposure on anti and pro-inflammatory cytokines in brain tissues. Our analysis shows that animals exposed to ELS present an increase in pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. On the other hand, no alteration was observed in the anti-inflammatory cytokine IL-10. Meta-regression revealed that alterations were more prominent in the hippocampus of adult animals that were exposed to more extended periods of ELS. These inflammatory effects were not permanent since few alterations were identified in aged animals. Our findings suggest that ELS exposure alters pro-inflammatory cytokines expression and may act as a primer for a secondary challenge that may induce lifelong immune alterations. Moreover, the actual evidence is insufficient to comprehend the relationship between anti-inflammatory cytokines and ELS fully.

Neurotrophic Factor Levels in Preterm Infants: A Systematic Review and Meta-Analysis.

Objectives: Through a systematic review and meta-analysis of the literature we aimed to compare the levels of BDNF, NGF, NT-3, NT-4, and GDNF between human term and preterm infants, and investigate factors implicated in the variability of effect size estimates. Methods: The analysis was performed in three online databases, MEDLINE Complete, PsycINFO, and CINAHL. A random effects model was used to calculate the standardized mean difference (SMD) of neurotrophic factor levels in preterm infants vs. term within a 95% confidence interval (CI). To explore sources of heterogeneity meta-regression models were implemented. Results: Sixteen studies were included in this meta-analysis. A combined sample of 1,379 preterm and 1,286 term newborns were evaluated. We identified significant lower BDNF (SMD = -0.32; 95% CI: -0.59, -0.06; p = 0.014) and NT-3 (SMD = -0.31; 95% CI: -0.52, -0.09; p = 0.004) levels in preterm compared to term infants. No significant difference was observed in NGF and NT-4 levels between groups. Given that only two effect sizes were generated for GDNF levels, no meta-analytical model was performed. Meta-regression models revealed sample type (placental tissue, cerebrospinal fluid, peripheral blood, and umbilical cord blood) as a significant moderator of heterogeneity for BDNF meta-analysis. No significant associations were found for gestational week, birth weight, and clinical comorbidity of newborns with effect sizes. Conclusions: Our findings indicated that lower BDNF and NT-3 levels may be associated with preterm birth. Future studies with larger samples sizes should investigate neurodevelopmental manifestations resulting from neurotrophic factor dysregulation among preterm infants.