Influence of early life events on immune reactivity in adult mice

Neveu, Pierre J.; Deleplanque, B.; Puglisi-Allegra, Stefano; D’Amato, Francesca R.; Cabib, Simona

doi:10.1002/dev.420270403

Cited by 38 publications

(13 citation statements)

References 23 publications

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“…A similar rebound has been observed in children recovering from stress (Doppman et al, 1986), and in mice injected with BCG (Meyer and Grundmann, 1980). In addition, and in line with previous studies that have indicated that some stress treatments may have immunopotentiating effects (Neveu et al, 1994), relative thymus weight showed an increase after the first stress session (Fig. 1); though note that severe stress is usually immunosuppressive Brosschot et al, 1994;Glaser and Kiecolt-Glaser, 1987;Keller et al, 1983;Pedersen et al, 1994;Schleifer et al, 1983).…”

Section: Non-programmed Changes In Thymussupporting

confidence: 82%

Evolution of the thymus size in response to physiological and random events throughout life

Domínguez-Gerpe

Rey-Méndez

2003

Microscopy Res & Technique

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During embryogenesis and in the early stages of life, the thymus is a crucial organ for the generation of the T cell repertoire. T cells are generated from hematopoietic stem cells already differentiated to precursor T cells in the bone marrow. These cells enter the thymus guided by chemotactic factors secreted by this organ. The complex maturation process takes place that ensures self-tolerance and homeostasis. Thymocytes that show autoreactivity do not leave the thymus, but rather die by apoptosis. The final percentage of mature T cells that survive to migrate from the thymus to the periphery is very low: at most 5%, under optimal conditions. The highest migration occurs in childhood and adulthood, at least in mice and humans; however, it declines throughout life and is minimal in the elderly. Under normal circumstances, the thymus commences involution soon after birth, and this involution correlates with the capacity to export mature T cells to the periphery. Hormones, cytokines, and neurotransmitters all play a role in this age-associated process, but the reasons for and mechanisms of this involution remain unknown. Apart from physiological conditions that change throughout life and govern age-related thymus evolution, random states and events provoked by intrinsic or extrinsic factors can induce either thymus involution, as in reversible transient thymic hypoplasias, or thymic hyperplasias. The age-associated involution, unlike transient involutions, follows a regular pattern for all individuals, though there are clear differences between the sexes. Nevertheless, even the age-associated involution seems to be reversible, raising the possibility of therapeutic strategies aimed at enhancing thymus function in the elderly.

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Section: Non-programmed Changes In Thymussupporting

confidence: 82%

Evolution of the thymus size in response to physiological and random events throughout life

Domínguez-Gerpe

Rey-Méndez

2003

Microscopy Res & Technique

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“…Evidence that environmental manipulations in newborn rat pups may lead to persistent changes in the endocrine, immune, and behavioral reactivity of adult rats is mounting (39,42,43,45). Neonatally stressed adult rats have decreased exploratory behavior in novel environments, a lower threshold for learned helplessness, and increased loss of hippocampal neurons associated with early onset cognitive defects compared to control groups of adult rats (36,39,45).…”

Section: Discussionmentioning

confidence: 99%

Long-Term Behavioral Effects of Repetitive Pain in Neonatal Rat Pups

Anand

Coskun

Thrivikraman

et al. 1999

Physiology & Behavior

388

273

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Human preterm neonates are subjected to repetitive pain during neonatal intensive care. We hypothesized that exposure to repetitive neonatal pain may cause permanent or long-term changes because of the developmental plasticity of the immature brain. Neonatal rat pups were stimulated one, two, or four times each day from P0 to P7 with either needle prick (noxious groups N 1 , N 2 , N 4 ) or cotton tip rub (tactile groups T 1 , T 2 , T 4 ). In groups N 2 , N 4 , T 2 , T 4 stimuli were applied to separate paws at hourly intervals; each paw was stimulated only once a day. Identical rearing occurred from P7 to P22 days. Pain thresholds were measured on P16, P22, and P65 (hot-plate test), and testing for defensive withdrawal, alcohol preference, air-puff startle, and social discrimination tests occurred during adulthood. Adult rats were exposed to a hot plate at 62°C for 20 s, then sacrificed and perfused at 0 and 30 min after exposure. Fos expression in the somatosensory cortex was measured by immunocytochemistry. Weight gain in the N 2 group was greater than the T 2 group on P16 (p < 0.05) and P22 (p < 0.005); no differences occurred in the other groups. Decreased pain latencies were noted in the N 4 group [5.0 ± 1.0 s vs. 6.2 ± 1.4 s on P16 (p < 0.05); 3.9 ± 0.5 s vs. 5.5 ±1.6 s on P22 (p < 0.005)], indicating effects of repetitive neonatal pain on subsequent development of the pain system. As adults, N 4 group rats showed an increased preference for alcohol (55 ± 18% vs. 32 ± 21%; p < 0.004); increased latency in exploratory and defensive withdrawal behavior (p < 0.05); and a prolonged chemosensory memory in the social discrimination test (p < 0.05). No significant differences occurred in corticosterone and ACTH levels following air-puff startle or in pain thresholds at P65 between N 4 © 1999 Elsevier Science Inc. 1 To whom requests for reprints should be addressed. anandsunny@exchange.uams.edu. and T 4 groups. Fos expression at 30 min after hot-plate exposure was significantly greater in all areas of the somatosensory cortex in the T 4 group compared with the N 4 group (p < 0.05), whereas no differences occurred just after exposure. These data suggest that repetitive pain in neonatal rat pups may lead to an altered development of the pain system associated with decreased pain thresholds during development. Increased plasticity of the neonatal brain may allow these and other changes in brain development to increase their vulnerability to stress disorders and anxietymediated adult behavior. Similar behavioral changes have been observed during the later childhood of expreterm neonates who were exposed to prolonged periods of neonatal intensive care. NIH Public Access KeywordsBehavioral effects; Repetitive pain; Rat pups Premature infants are often exposed to repetitive invasive procedures causing acute pain during the course of neonatal intensive care (4). These experiences occur during a critical window of increased plasticity in the developing brain (32,48 Human infants and neonatal rat pups display a vari...

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“…5). Neonatal handling in mice enhances cell-mediated immune responses such as NK cell cytotoxicity and mitogen-induced lymphocyte proliferation in adult mice (30). In contrast, differences in immune responsiveness between handled and nonhandled rats were not as pronounced or have not been consistently observed for either antibody responses or predisposition to tumors (31,32).…”

Section: Postnatal Environment and Maternal Factorsmentioning

confidence: 94%

The maternal-neonatal neuro-immune interface: Are there long-term implications for inflammatory or stress-related disease?

Shanks

Lightman²

2001

J. Clin. Invest.

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Inflammatory stimuli reliably elicit hypothalamic-pituitary-adrenal (HPA) activation, and it is now established that the immune and HPA systems are mutually regulatory and that their interactions partly determine stress effects on immune function. What has not been extensively investigated, however, is the interactive nature of the development of the endocrine and immune systems and whether this might alter predisposition to inflammatory disease or stress-related pathologies. Increasing attention is now being focused on the role of early life environments determining longterm predisposition to disease, and a role for the HPA axis in disease predisposition is emerging.Stress generally refers to the condition where coping with actual or perceived stimuli alters the homeostatic state of the organism. The classic stress response involves the activation of central and peripheral catecholamine systems and HPA responses. Increased glucocorticoid levels are thought to protect the organism, both by providing energy substrates to deal with immediate environmental demands and by blocking potentially harmful overreaction by the immune system and other stress-reactive systems (1). However, to avoid immunosuppression and degenerative pathologies associated with increased glucocorticoid levels, the HPA stress response must terminate efficiently once the environmental demands are removed (2). Consequently, disturbances in endocrine-immune interactions upset the normal regulatory homeostatic balance and alter susceptibility to a variety of disease states associated with immune dysregulation (3).The physiological impact of stress is variable across individuals, and susceptibility to stress apparently depends on attributes of the organism, such as genetic endowment and age, and experiential factors, such as previous stress experiences, and early life events (4, 5). Indeed, the endocrine and immune systems and the CNS all respond to environmental pressures during development, and the interactive nature of these systems suggests that alterations in one system could have developmental consequences for the others and potential long-term implications for disease vulnerability. Plasticity in most developing physiological systems is thought to be of adaptive importance, enabling an organism to better meet the demands of the environment in which it matures and will most likely reside. However, the short-term reorganization or re-setting of regulatory systems to deal with immediate demands may also have long-term consequences for normal physiological function, thereby predisposing an organism to pathology. This may particularly be the case when the environmental pressures differ between development and adulthood.A number of epidemiological studies have indicated that nutritional factors early in life have long-term implications for cardiovascular and metabolic disease in adulthood. Most data suggest that maternal nutrition and limited intrauterine growth are responsible for reorganizing metabolic regulation and results in metabolic and car...

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Influence of early life events on immune reactivity in adult mice

Cited by 38 publications

References 23 publications

Evolution of the thymus size in response to physiological and random events throughout life

Evolution of the thymus size in response to physiological and random events throughout life

Long-Term Behavioral Effects of Repetitive Pain in Neonatal Rat Pups

The maternal-neonatal neuro-immune interface: Are there long-term implications for inflammatory or stress-related disease?

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