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Effect of maternal separation and maternal deprivation on the growth and metastatization of murine melanoma B16F10 and on the immune response regulation: analysis of hipotalamic-pituitary-adrenal axis activation

Grant number: 08/06036-9
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): July 01, 2009
Effective date (End): June 30, 2012
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Deborah Suchecki
Grantee:Beatriz Helena Pizarro de Lorenzo
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Among the environmental factors that may determine individual differences in stress response, disruption of the mother-infant relationship is one of the most powerful ones. Brief maternal separations (BMS) normally result in adequate response to stress and less fear and anxiety behaviours, as well as more efficient negative feedback mechanism. In contrast, pups submitted to long maternal separation (LMS) usually become hyperresponsive to stress. Another animal model that mimics the consequences of the disruption of the dam-pup interaction (as a model of loss of one or both parents) is the 24h maternal deprivation (PM) paradigm. Immediately after the deprivation period, pups show increase in basal, post-stress and ACTH -induced corticosterone (CORT) during the stress hyporesponsive period. Therefore, maternal presence serves not only as a source of heat, nutrition and cleansing of the offspring, but also regulates many physiological, behavioral and psychological processes. In humans, neglect in early life can lead to psychological consequences in adult life, like greater susceptibility to develop anxiety and depression. Studies with animal models show that in adulthood rats and C57BL / 6 mice have high levels of anxiety when subjected to long maternal separation (LMS) and that this disturbance causes increase in the HPA response to acute stress. In humans, stress effects on immune function are being analised in transverse and longitudinal studies. At the cellular level, stressed or depressed patients show relevant alterations in components of the immune system, including low efficacy when challenged with various stimuli. Studies have shown that stress and depression may promote tumor progression. Evidence from animal and human studies suggests that stress induces disability of the immune response by stimulating the beginning and progression of some types of cancer. With the activation of the HPA, the mediators released during the stress response suppress specific and non-specific immune mediators, compromising the anti-tumoral immune response. Therefore, the goal of the present proposal is to investigate the possible implications of maternal separation and maternal deprivation as risk factors to and the participation of the HPA axis in the progression and metastatization of murine melanoma B16F10 in C57BL/6 mice. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE LORENZO, BEATRIZ H. P.; MARCHIORO, LAIS DE OLIVEIRA; GRECO, CAROLLINA RIBEIRO; SUCHECKI, DEBORAH. Sleep-deprivation reduces NK cell number and function mediated by beta-adrenergic signalling. PSYCHONEUROENDOCRINOLOGY, v. 57, p. 134-143, . (08/06036-9)

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