Tracing the trajectory of behavioral impairments and oxidative stress in an animal model of neonatal inflammation

MacRae, M.; Macrina, T.; Khoury, Antoine E.; Migliore, Mattia M.; Kentner, Amanda C.

doi:10.1016/j.neuroscience.2015.04.048

Cited by 38 publications

(33 citation statements)

References 67 publications

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“…Therefore, the ratio of oxidative stress to anti-oxidant may uncover MS effects that were not observed here. Indeed, as previously described, rearing in an enriched environment can protect against adolescent PFC oxidative stress after a neonatal inflammatory insult (MacRae et al, 2015). We also note that the PFC tissue analyzed was not free of blood contamination, which potentially interfered with oxidative stress measures.…”

Section: Discussionsupporting

confidence: 65%

“…We have reported that males but not females expressed heightened cyclooxygenase‐2 in the PFC after MS (Holland et al, ), suggesting that males may be more vulnerable than females to the inflammatory consequences of early life stress. Further supporting this hypothesis are the reports that males are more sensitive than females to the long‐term effects of early‐life immune challenges (Bilbo, Smith, & Schwarz, ; MacRae et al, ; Schwarz & Bilbo, ), and that the effect of MS on later endotoxin‐induced sickness behavior is more severe in males compared to females (Avitsur & Sheridan, ). The developmental mechanisms underpinning these sex‐dependent effects are not known.…”

Section: Discussionmentioning

confidence: 90%

“…Protective effects of EE have been most readily studied in the hippocampus, with compelling evidence that EE prevents against MS-induced decreases in N-acetylaspartate-a mitochondrial protein associated with energy production (Hui et al, 2011). Although fewer investigations have studied the effects of EE on the PFC after early life stress, recent data demonstrate that rearing in an enriched environment can protect against adolescent PFC oxidative stress after a neonatal inflammatory insult (MacRae, Macrina, Khoury, Migliore, & Kentner, 2015). Furthermore, in typically developing and aged animals and humans, EE has anti-inflammatory (Arranz et al, 2010) and anti-oxidant effects (Sampedro-Piquero, Zancada-Menendez, Begega, Rubio, & Arias, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Effects of early adolescent environmental enrichment on cognitive dysfunction, prefrontal cortex development, and inflammatory cytokines after early life stress

Prado

Narahari

Holland

et al. 2015

Developmental Psychobiology

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Early postnatal stress such as maternal separation causes cognitive dysfunction later in life, including working memory deficits that are largely mediated by the prefrontal cortex. Maternal separation in male rats also yields a loss of parvalbumin-containing prefrontal cortex interneurons in adolescence, which may occur via inflammatory or oxidative stress mechanisms. Environmental enrichment can prevent several effects of maternal separation; however, effects of enrichment on prefrontal cortex development are not well understood. Here, we report that enrichment prevented cognitive dysfunction in maternally separated males and females, and prevented elevated circulating pro-inflammatory cytokines that was evident in maternally separated males, but not females. However, enrichment did not prevent parvalbumin loss or adolescent measures of oxidative stress. Significant correlations indicated that adolescents with higher oxidative damage and less prefrontal cortex parvalbumin in adolescence committed more errors on the win-shift task; therefore, maternal separation may affect cognitive dysfunction via aberrant interneuron development. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 58: 482-491, 2016.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of early adolescent environmental enrichment on cognitive dysfunction, prefrontal cortex development, and inflammatory cytokines after early life stress

Prado

Narahari

Holland

et al. 2015

Developmental Psychobiology

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“…Enhanced environmental stimulation, in the form of EE, has been shown to affect the structure and underlying plasticity of the neonatal rodent brain (He, Ma, Liu, & Yu, 2010;Malkasian & Diamond, 1971), suggesting that EE has potential translational utility in early development. As might be predicted, EE exposure during the early prenatal and/or neonatal periods is protective (Brummelte, Neddens, & Teuchert-Noodt, 2007;Connors, et al, 2014;Cymerblit-Sabba et al, 2013;MacRae, Macrina, Khoury, Migliore, & Kentner, 2015;Pedrini Schuch et al, 2016;Welberg et al, 2006). This is important because animal studies that investigate prevention have largely focused on pharmacotherapies rather than environmental interventions.…”

Section: Harnessing the Environment To Promote Resiliency To Early mentioning

confidence: 99%

Resilience priming: Translational models for understanding resiliency and adaptation to early life adversity

Kentner

Cryan

Brummelte

2018

Developmental Psychobiology

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Despite the increasing attention to early life adversity and its long‐term consequences on health, behavior, and the etiology of neurodevelopmental disorders, our understanding of the adaptations and interventions that promote resiliency and rescue against such insults are underexplored. Specifically, investigations of the perinatal period often focus on negative events/outcomes. In contrast, positive experiences (i.e. enrichment/parental care//healthy nutrition) favorably influence development of the nervous and endocrine systems. Moreover, some stressors result in adaptations and demonstrations of later‐life resiliency. This review explores the underlying mechanisms of neuroplasticity that follow some of these early life experiences and translates them into ideas for interventions in pediatric settings. The emerging role of the gut microbiome in mediating stress susceptibility is also discussed. Since many negative outcomes of early experiences are known, it is time to identify mechanisms and mediators that promote resiliency against them. These range from enrichment, quality parental care, dietary interventions and those that target the gut microbiota.

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“…For example, males are at much higher risk of immune-related neurodevelopmental disorders such as ASD (Baio et al, 2018) while females are far more likely than males to develop autoimmune disorders such as lupus erythematosus, myasthenia gravis, and thyroid diseases including Graves disease and Hashimotos thyroiditis (Klein & Flanagan, 2016), as well as anxiety and depression (Hodes & Epperson, 2019). While several studies have investigated the impact of neonatal LPS challenge on behavioral outcomes and/or microglia (Peng et al, 2019;Bukhari et al, 2018;MacRae et al, 2015;Williamson et al, 2011;Schwarz & Bilbo, 2011;Rico et al, 2010), few of these studies have included both males and females in their analysis, especially in the context of social behavior (Taylor et al, 2012;Kentner et al, 2018;Carlezon et al, 2019). Given that females have traditionally been underrepresented in such studies (Beery & Zucker, 2011;Klein & Flanagan, 2016) it is critical that we gain a better understanding of the long-term consequences of neonatal inflammation in females.…”

Section: Introductionmentioning

confidence: 99%

Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number, independent of microglial inflammatory signaling

Smith

Kingsbury

Dziabis

et al. 2020

Preprint

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Decreases in social behavior are a hallmark aspect of acute "sickness behavior" in response to infection.However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits.Microglia, the resident immune cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females.Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC.Finally, these changes in social behavior and SST cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNFα and IL-1β) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, independent of microglial inflammatory signaling.

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Tracing the trajectory of behavioral impairments and oxidative stress in an animal model of neonatal inflammation

Cited by 38 publications

References 67 publications

Effects of early adolescent environmental enrichment on cognitive dysfunction, prefrontal cortex development, and inflammatory cytokines after early life stress

Effects of early adolescent environmental enrichment on cognitive dysfunction, prefrontal cortex development, and inflammatory cytokines after early life stress

Resilience priming: Translational models for understanding resiliency and adaptation to early life adversity

Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number, independent of microglial inflammatory signaling

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