Neonatal Programming by Neuroimmune Challenge: Effects on Responses and Tolerance to Septic Doses of Lipopolysaccharide in Adult Male and Female Rats

Spencer, Sarah J.; Pittman, Quentin J.

doi:10.1111/j.1365-2826.2010.01967.x

Cited by 24 publications

(24 citation statements)

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“…However, it is also known that lack of exposure to appropriate immune stimuli in childhood can enhance the risk of developing autoimmune diseases (62,73). We have seen in the rodent that a P14 challenge with LPS does not lead to obvious deficits in the later life ability to respond to a dose of LPS sufficicent to produce sepsis (79). We have also seen minimal effects on the animals' behavioral profiles (80).…”

Section: Discussionmentioning

confidence: 57%

“…In support of a critical role for TLRs in the programming response, we found that there was no alteration to the corticosteroid response to restraint stress after neonatal LPS or to the brief stress-induced hyperthermia in response to the needle prick of the injection (61,79). However, it is interesting to note that, in a recent study by Soriano and Branco in which they examined open-field-induced stress fever in rats treated at P14 with LPS (76), there was a corticosterone-dependent attenua- Fig.…”

Section: Mechanisms Of Neonatal Programming Of Adult Immune Functionmentioning

confidence: 82%

“…These findings therefore describe a long-lasting altered innate immune response following a single low-dose immune challenge that is encountered, in the rat, at a developmental period after P7 and before P28. These alterations in innate immune function with neonatal LPS also appear to be independent of any changes in both the anorectic and anhedonic responses to LPS (47,79).…”

Section: Neonatal Programming Of Adult Immune Responsesmentioning

confidence: 97%

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Neonatal programming of innate immune function

Spencer

Galic

Pittman

2011

American Journal of Physiology-Endocrinology and Metabolism

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The early life environment can be crucial in influencing the development of an animal's long-term physiology. There is now much evidence to suggest that perinatal challenges to an animal's immune system will result in changes in adult rat behavior, physiology, and molecular pathways following a single inflammatory event during development caused by the bacterial endotoxin lipopolysaccharide (LPS). In particular, it is now apparent that neonatal LPS administration can influence the adult neuroimmune response to a second LPS challenge through hypothalamic-pituitary-adrenal axis modifications, some of which are caused by alterations in peripheral prostaglandin synthesis. These pronounced changes are accompanied by a variety of alterations in a number of disparate aspects of endocrine physiology, with significant implications for the health and well-being of the adult animal. In this review, we discuss the newly elucidated mechanisms by which neonatal immune challenge can permanently alter an animal's endocrine and metabolic physiology and the implications this has for various disease states.lipopolysaccharide; fever; hypothalamic-pituitary-adrenal axis Early Life Events Program Physiology Long TermEARLY LIFE EVENTS can have significant long-term effects on an animal's physiology. In humans, an adverse early life experience such as emotional neglect can lead to an increased likelihood of the individual developing anxiety, depression, chronic illness, even drug addiction, in later life (15,32,39,54). Similar findings have been demonstrated in primate models, with parental or social deprivation during the neonatal period producing socially maladjusted, timid, depressed adults that have alterations in neuroimmune and hypothalamic-pituitary-adrenal (HPA) axis function (32,75). In rodents, too, an experience as subtle as a brief period of handling or withdrawal of maternal attention can have pronounced effects on physiology and behavior throughout the life of the animal. For instance, seminal work by Meaney and colleagues has revealed that parenting style, categorized by high-vs. low-intensity nursing and grooming, can program anxiety levels and responsiveness of the HPA axis in the offspring. Thus, rats nursed by dams that impart low-intensity nursing/grooming have exacerbated HPA axis responses to stress (19, 53). They also have alterations in other functions, ranging from their ability to perform cognitive tasks (52) to sexual behavior (17).Early life events other than social and maternal contact can also have an impact upon the animal's physiology long term. For instance, neonatal overfeeding can lead to obesity in adulthood coupled with changes to anxiety and HPA axis responses to stress (84). Also, a painful inflammatory event experienced at critical time points during development alters perception of a painful stimulus in later life (4). Clearly, the early postnatal developmental period is important in programming adult physiology.One of the more common types of physical stimulus encountered during childhood is an...

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Section: Discussionmentioning

confidence: 57%

Section: Mechanisms Of Neonatal Programming Of Adult Immune Functionmentioning

confidence: 82%

Section: Neonatal Programming Of Adult Immune Responsesmentioning

confidence: 97%

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Neonatal programming of innate immune function

Spencer

Galic

Pittman

2011

American Journal of Physiology-Endocrinology and Metabolism

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“…These results collectively suggest that the human immune system responds to particular adverse experiences during critical developmental stages, and that the immune system may remain activated into adulthood. Although, it has yet to be studied during puberty, immune challenge during another developmental stage – neonatal -- in rodents causes long-term changes in the immune system (Spencer et al, 2006a; Spencer et al, 2010; Spencer et al, 2006b). …”

Section: Relevance To Humans: Some Questions and A Hypothesismentioning

confidence: 99%

Enduring influence of pubertal stressors on behavioral response to hormones in female mice

Blaustein

Ismail

2013

Hormones and Behavior

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The pubertal period is a time of change in an animal’s response to stress, and it is a second period of sexual differentiation of the brain. Recently, it was discovered that particular stressors during the prolonged pubertal period of female mice result in enduring changes in behavioral responsiveness of the brain to estradiol and progesterone. Depending on the behavior, pubertal immune challenge or shipping from suppliers may decrease, eliminate, or even reverse the effects of estradiol. Pubertal immune challenge results in changes in the number of estrogen receptor-immunoreactive cells in key brain areas suggesting a cellular mechanism for this remodeling of the brain’s response to hormones. A hypothesis is put forward that predicts that particular adverse experiences in girls may cause long-term alterations in the brain’s response to estradiol and/or progesterone via activation of the immune system. This could lead to mood disorders or altered response to any behavior influenced by estradiol in humans.

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“…We compared all behavioral and histological scores for the 24-h group using 2 ϫ 2 between-group ANOVA with genotype (wt and ghrϪ/Ϫ) and surgery (sham and 2VO) as between factors, followed by one-way ANOVA with Student-Newman-Keuls post hocs as appropriate. Temperature data were used to derive a temperature index (°C ϫ hour), as we have described previously (9,63) for the 24 h after surgery. That is, the temperatures at each 10-min interval were averaged over the first 30 min to calculate a baseline for each period.…”

Section: Discussionmentioning

confidence: 99%

Endogenous ghrelin's role in hippocampal neuroprotection after global cerebral ischemia: does endogenous ghrelin protect against global stroke?

Kenny

Cai

Bayliss

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Ghrelin is a gastrointestinal hormone with a well-characterized role in feeding and metabolism. Recent evidence suggests that ghrelin may also be neuroprotective after injury in animal models of cerebral ischemia. Thus exogenous ghrelin treatment can improve cell survival, reduce infarct size, and rescue memory deficits in focal ischemia models, doing so by suppressing inflammation and apoptosis. Endogenous ghrelin plays a key a role in a number of physiological processes, including feeding, metabolism, stress, and anxiety. However, no study has examined whether endogenous ghrelin also contributes to neuroprotection after cerebral ischemia. Here, we aimed to determine whether endogenous ghrelin normally protects against neuronal cell death and cognitive impairments after global cerebral ischemia and whether such changes are linked with inflammation or apoptosis. We used a two-vessel occlusion (2VO) model of global cerebral ischemia in wild-type (wt) and ghrelin knockout (ghr-/-) C57/Bl6J mice. ghr-/- mice had improved cell survival in the Cornu Ammonis(CA)-2/3 region of the hippocampus-a region of significant growth hormone secretagogue receptor expression. They also displayed less cellular degeneration than wt mice after the 2VO (Fluoro-Jade) and had less cognitive impairment in the novel object-recognition test. These outcomes were despite evidence of more neuroinflammation and apoptosis in the ghr-/- and less of a postsurgery hypothermia. Finally, we found that mortality in the week following the 2VO was reduced more in ghr-/- mice than in wt. Overall, these experiments point to a neurodegenerative but antiapoptotic effect of endogenous ghrelin in this model of global ischemia, highlighting that further research is essential before we can apply ghrelin treatments to neurodegenerative insults in the clinic.

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Neonatal Programming by Neuroimmune Challenge: Effects on Responses and Tolerance to Septic Doses of Lipopolysaccharide in Adult Male and Female Rats

Cited by 24 publications

References 50 publications

Neonatal programming of innate immune function

Neonatal programming of innate immune function

Enduring influence of pubertal stressors on behavioral response to hormones in female mice

Endogenous ghrelin's role in hippocampal neuroprotection after global cerebral ischemia: does endogenous ghrelin protect against global stroke?

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