Neonatal immune challenge does not affect body weight regulation in rats

Spencer, Sarah J.; Mouihate, Abdeslam; Galic, Michael A.; Ellis, Shaun; Pittman, Quentin J.

doi:10.1152/ajpregu.00262.2007

Cited by 40 publications

(34 citation statements)

References 64 publications

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“…Importantly, the increase in the levels of these cytokines in the circulation was dissociated from the attenuated brain inflammation observed in our studies, and therefore negates their influence on the observed changes in neutrophil recruitment and favors the direct action of leptin on the brain as reported in this study. Interestingly, leptin levels were not affected by the LPS treatment in our experiments (Supplementary Table S1), in agreement with some 59,60 but contrary to other [16][17][18] studies. The reason for this apparent discrepancy is currently unclear, but the relatively late time point chosen in this study (24 h) may have not been ideal for the detection of LPS-induced leptin increase.…”

Section: Discussionsupporting

confidence: 92%

Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation

et al. 2009

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The appetite suppressing hormone leptin has emerged as an important modulator of immune function and is now considered to be a critical link between energy balance and host defense responses to pathogens. These 'adaptive' responses can, in situations of severe and sustained systemic inflammation, lead to adverse effects including brain damage that is partly mediated by neutrophil recruitment into the brain. We examined the contribution of leptin to this process in leptin-deficient (ob/ob), -resistant (db/db) and wild-type (WT) mice injected intraperitoneally with a septic dose of lipopolysaccharide (LPS). This treatment induced a dramatic increase in the number of neutrophils entering the brain of WT mice, an effect that was almost totally abolished in the mutant mice and correlated with a significant reduction in the mRNA levels of interleukin-1b, intracellular adhesion molecule-1 and neutrophil-specific chemokines. These effects were reversed with leptin replenishment in ob/ob mice leading to recovery of neutrophil recruitment into the brain. Moreover, 48 h food deprivation in WT mice, which decreased circulating leptin levels, attenuated the LPS-induced neutrophil recruitment as did a single injection of an anti-leptin antiserum 4 h before LPS treatment in WT mice. These results provide the first demonstration that leptin has a critical role in leukocyte recruitment to the brain following severe systemic inflammation with possible implications for individuals with altered leptin levels such as during obesity or starvation.

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Section: Discussionsupporting

confidence: 92%

Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation

et al. 2009

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“…Conversely, P14 is a point in development where HPA axis responsiveness to stress begins to acquire an adult-like profile (50), potentially a vulnerable stage in the development of HPA axis function. In this regard, we have also observed, under some housing conditions, changes in adult body weight after an LPS challenge at P7 (82,83), an observation that has been replicated in rats treated at P10 (42). The hypothalamic pathways regulating body weight and metabolism are known to mature, in the rodent, between P6 and P12 (2, 13), making this a particularly sensitive time for these pathways.…”

Section: Unresolved Issuessupporting

confidence: 61%

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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“…This dose was chosen because it has been shown to induce behavioral and endocrine alterations and to increase cytokines at the placental level [12,13]. The estrous phase was chosen to standardize the female hormonal status.…”

Section: Methodsmentioning

confidence: 99%

Temporal Analysis of Lipopolysaccharide-Induced Sickness Behavior in Virgin and Lactating Female Rats

Nascimento

Bernardi

Pecorari

et al. 2013

Neuroimmunomodulation

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Objectives: Lipopolysaccharide (LPS), an endotoxin that originates from the cell wall of Gram-negative bacteria, activates the immune system to release proinflammatory cytokines and to induce sickness behavior. The present study sought to characterize the time-dependent effects of LPS on fever, body weight, and food and water consumption in female virgin and lactating rats exposed to an LPS dose previously reported to induce sickness behavior in pregnant female rats. Methods: Virgin female Wistar rats in the estrous phase and lactating female Wistar rats on the third day of lactation received 100 µg/kg LPS or saline solution. Tympanic temperature, body weight, and food and water consumption were assessed 0, 2, 24, 48, 72, 96, and 120 h after treatment. Results: In lactating female rats, tympanic temperature was attenuated compared with virgin females. Food consumption and body weight gain in both groups decreased, but lactating rats consumed more food than virgin rats. Water consumption increased at different time points. Conclusion: LPS exposure induced several signs of sickness behavior, including decreases in food consumption and body weight gain, and induced adipsia in both virgin and lactating female rats. Because the time course and profile of fever varied between lactating and nonlactating animals, these responses appeared to depend on the physiological state of female animals.

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Neonatal immune challenge does not affect body weight regulation in rats

Cited by 40 publications

References 64 publications

Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation

Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation

Neonatal programming of innate immune function

Temporal Analysis of Lipopolysaccharide-Induced Sickness Behavior in Virgin and Lactating Female Rats

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