Maternal separation of rat pups increases the risk of developing depressive-like behavior after subsequent chronic stress by altering corticosterone and neurotrophin levels in the hippocampus

Marais, Lelanie; Rensburg, Susan J. van; Zyl, Johann M. van; Stein, Dan J.; Daniels, Willie M. U.

doi:10.1016/j.neures.2008.01.011

Cited by 181 publications

(116 citation statements)

References 52 publications

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“…In agreement with our results, it has experimentally been demonstrated that prolonged episodes of MS during the first weeks of life induced depression-like behaviour in adult rats [5,35], including studies [46]. The main finding of this research is that dietary supplementation with methyl donors in adulthood reversed the immobility time in the Porsolt forced swimming test, ameliorating the depression-like phenotype induced by MS.…”

Section: Discussionsupporting

confidence: 91%

Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour

Paternain

Martišová

Campión

et al. 2016

Behavioural Brain Research

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Adverse early life events are associated with altered stress responsiveness and metabolic disturbances in the adult life. Dietary methyl donor supplementation could be able to reverse the negative effects of maternal separation by affecting DNA methylation in the brain. In this study, maternal separation during lactation reduced body weight gain in the female adult offspring without affecting food intake, and altered total and HDLcholesterol levels. Also, maternal separation induced a cognitive deficit as measured by NORT and an increase in the immobility time in the Porsolt forced swimming test, consistent with increased depression-like behaviour. An 18-week dietary supplementation with methyl donors (choline, betaine, folate and vitamin B12) from postnatal day 60 also reduced body weight without affecting food intake. Some of the deleterious effects induced by maternal separation, such as the abnormal levels of total and HDL-cholesterol, but especially the depression-like behaviour as measured by the Porsolt test, were reversed by methyl donor supplementation. Also, the administration of methyl donors increased total DNA methylation (measured by immunohistochemistry) and affected the expression of insulin receptor in the hippocampus of the adult offspring. However, no changes were observed in the DNA methylation status of insulin receptor and corticotropin-releasing hormone (CRH) promoter regions in the hypothalamus. In summary, methyl donor supplementation reversed some of the deleterious effects of an early life-induced model of depression in rats and altered the DNA methylation profile in the brain.

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Section: Discussionsupporting

confidence: 91%

Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour

Paternain

Martišová

Campión

et al. 2016

Behavioural Brain Research

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“…In addition, animal experiments with early or/and adult stresses revealed more depression-like symptoms in animals that had experienced early stress. For example, Marais and Øines groups (Marais et al 2008;Øines et al 2012) induced early stress in rats by maternal separation after birth and found that these rats in adulthood consumed less fluid than the control animals (Øines et al 2012). If a second restraint-stress was induced in these rats, the animals in the double stress group were less capable of swimming for 15 minutes on day 65 (Marais et al 2008).…”

Section: Introductionmentioning

confidence: 99%

“…For example, Marais and Øines groups (Marais et al 2008;Øines et al 2012) induced early stress in rats by maternal separation after birth and found that these rats in adulthood consumed less fluid than the control animals (Øines et al 2012). If a second restraint-stress was induced in these rats, the animals in the double stress group were less capable of swimming for 15 minutes on day 65 (Marais et al 2008). These results suggest that an early life adversity leads to animals to exhibit more severe depression-like behavior in response to adulthood stress.…”

Section: Introductionmentioning

confidence: 99%

Blunted Behavioral and Molecular Responses to Chronic Mild Stress in Adult Rats with Experience of Infancy Maternal Separation

Shu

Xiao

Tang³

et al. 2015

Tohoku J. Exp. Med.

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Childhood adversity has profound and persistent effects on brain functions and has been implicated in the etiology of depression. Brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) play critical roles during brain development to maintain neuronal function and structural integrity in adulthood. We therefore investigated the long-term effects of early life adversity on the depression-related behavior and the expression of BDNF and CREB in the hippocampus. Male SpragueDawley newborn rats were subjected to maternal separation for 3 h/day on postnatal days 2-14. After the postnatal day 90, rats with or without the experience of infancy maternal separation received a series of unpredictable chronic mild stress (CMS) for 21 days. Sucrose preference and spontaneous activity in the open field test were recorded, and the expression of BDNF and CREB in the hippocampus was measured by real-time RT-PCR and Western blot analyses. Before exposure to CMS, the rats with maternal separation showed the significant decreases in sucrose preference, spontaneous activity, and hippocampal expression of BDNF and CREB, compared to the animals without maternal separation. In contrast, the rats without maternal separation showed greater decreases of the above indictors after CMS, the levels of which were lower than those observed in the rats with maternal separation. Thus, early life adversity leads to long-term decreases in the capacity of enjoying sweetness, spontaneous activity, and hippocampal expression of BDNF and CREB. Moreover, childhood neglect may decrease the neurobehavioral plasticity, thereby blunting the responses to adulthood stress and increasing the susceptibility to depression.

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“…Growth factors have also been implicated in depression [66], as depression-like behavior has been associated with reduced NGF and IGF1 levels in the rat brain [67,68]. Altered NGF levels have been shown to increase the risk of developing depression after chronic stress [69], while 19 antidepressant drugs have been shown to have a beneficial impact of on the malfunction of IGF1 in adult rats [70]. NGF levels of mothers with postpartum affective disorders are also correlated with infant development [71].…”

Section: Common Regulators and Targets Of The Maternally Altered Protmentioning

confidence: 99%

Maternal alterations in the proteome of the medial prefrontal cortex in rat

Völgyi

Udvari²,

Szabó³

et al. 2017

Journal of Proteomics

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Proteomic differences between rat dams and control mothers deprived of their pups immediately after delivery were investigated in the medial prefrontal cortex (mPFC).A 2-D DIGE minimal dye technique combined with LC-MS/MS identified 32 different proteins that showed significant changes in expression in the mPFC, of which, 25were upregulated and 7 were downregulated in dams. The identity of one significantly increased protein, the small heat-shock protein alpha-crystallin B chain (Cryab), was confirmed via Western blot analysis. Alpha-crystallin B chain was distributed in scattered cells in the mPFC, as demonstrated by immunohistochemistry. Furthermore, it was found to be localized in parvalbumin-containing neurons using double labeling. The elevation of its mRNA level in rat dams was also demonstrated via RT-PCR.The functional classification of the altered proteins was conducted using the UniProt and Gene Ontology protein databases. The identified proteins predominantly participate in synaptic transport and plasticity, neuron development, oxidative stress and apoptosis, and cytoskeleton organization. A common regulator and target analysis of these proteins determined using the Elsevier Pathway Studio Platform suggests that protein level changes associated with pup nursing are driven by growth factors and cytokines, while the MAP kinase pathway was identified as a common target. A high proportion of the proteins that were found to be altered in the mPFC are associated with depression. Biological significanceThe behavior and emotional state of females change robustly when they become mothers. The brain, which governs these changes, may also undergo molecular alterations in mothers. As no proteomics approaches have been applied regarding maternal changes in the brain, we addressed this issue in the mPFC as this brain area is the uppermost cortical center Alpha-crystallin B chain, a protein confirmed to be increased during maternal behaviors, was selectively found in parvalbumin cells, which, as fast-spiking interneurons, are associated with depression. The function of alpha-crystallin B chain should be further investigated to establish whether it can be used to identify drug targets for future drug development.

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Maternal separation of rat pups increases the risk of developing depressive-like behavior after subsequent chronic stress by altering corticosterone and neurotrophin levels in the hippocampus

Cited by 181 publications

References 52 publications

Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour

Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour

Blunted Behavioral and Molecular Responses to Chronic Mild Stress in Adult Rats with Experience of Infancy Maternal Separation

Maternal alterations in the proteome of the medial prefrontal cortex in rat

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