Neonatal repetitive maternal separation causes long-lasting alterations in various neurotrophic factor expression in the cerebral cortex of rats

Lee, Kyoung-Youl; Miki, Takanori; Yokoyama, Toshifumi; Ueki, Masaaki; Warita, Katsuhiko; Suzuki, Shingo; Ohta, Kenichi; Wang, Zhiyu; Jamal, Mostofa; Yakura, Tomiko; Liu, Jun-Qian; Hosomi, Naohisa; Takeuchi, Yoshiki

doi:10.1016/j.lfs.2012.01.021

Cited by 28 publications

(19 citation statements)

References 67 publications

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“…Altered BDNF in the hippocampus and the amygdala has been previously associated with anxiolytic and antidepressant behaviour by us 26 and others 25,27 , but in the present study, we did not find a overall correlation between BDNF levels and mouse behaviour, except for the increased levels of hippocampal BDNF and decreased behavioural despair in MS GF male mice. Controversial results emerge from previous studies of hippocampal BDNF in SPF mice following MS: some reported higher [46][47][48] and others lower BDNF levels 9,49,50 in MS rodents. These controversies may thus represent a combined, and sometime opposing, effects of MS and gut microbiota on the brain and behaviour.…”

Section: P=0030mentioning

confidence: 96%

Microbiota and host determinants of behavioural phenotype in maternally separated mice

et al. 2015

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Early-life stress is a determinant of vulnerability to a variety of disorders that include dysfunction of the brain and gut. Here we exploit a model of early-life stress, maternal separation (MS) in mice, to investigate the role of the intestinal microbiota in the development of impaired gut function and altered behaviour later in life. Using germ-free and specific pathogen-free mice, we demonstrate that MS alters the hypothalamic-pituitary-adrenal axis and colonic cholinergic neural regulation in a microbiota-independent fashion. However, microbiota is required for the induction of anxiety-like behaviour and behavioural despair. Colonization of adult germ-free MS and control mice with the same microbiota produces distinct microbial profiles, which are associated with altered behaviour in MS, but not in control mice. These results indicate that MS-induced changes in host physiology lead to intestinal dysbiosis, which is a critical determinant of the abnormal behaviour that characterizes this model of early-life stress.

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Section: P=0030mentioning

confidence: 96%

Microbiota and host determinants of behavioural phenotype in maternally separated mice

et al. 2015

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“…However, in the cerebral cortex, the levels of expression of BDNF and IGF-1 mRNA and the mRNA of their respective receptors, TrkB and IGF-1R, were enhanced on PND16 and PND20, and they then returned to normal levels on PND30. However, the levels of expression were decreased on PND60 22) . These results have led us to the conclusion that the effects of neonatal maternal separation on the cerebellum were different from those on the hippocampus and the cerebral cortex.…”

Section: Discussionmentioning

confidence: 95%

“…We have previously demonstrated that the repetitive maternal separation of rat neonates during PND10-15 cause drastic, long-lasting, and abnormal fluctuations of various neurotrophic factors in the hippocampus and the cerebral cortex 20,22) . In the hippocampus, BDNF expression was attenuated on PND16 and then increased on PND60.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously examined the effects of early postnatal maternal separation stress on the levels of expression of neurotrophic factor ligands/receptors in various brain regions, including the hippocampus and the cerebral cortex, of rats [20][21][22] . The neurotrophic factor levels were different in the different time points and brain regions that were examined.…”

Section: Introductionmentioning

confidence: 99%

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Differential effects of neonatal maternal separation on the expression of neurotrophic factors in rat brain. II: Regional differences in the cerebellum versus the cerebral cortex

Miki

Lee

Yokoyama

et al. 2013

Okajimas Folia Anat. Jpn.

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Summary: This study was conducted in order to examine the effects of early postnatal maternal separation stress on the age-dependent fluctuations in the expression levels of neurotrophic factor ligands and receptors in the developing cerebellum. Wistar rats were separated from their mothers for 3 h each day during postnatal days (PND) 10 to 15. The expression level of mRNA for brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), insulin-like growth factor-1 (IGF-1), and type-1 IGF receptor (IGF-1R) were evaluated in the cerebellum on PND16, 20, 30, and 60 with real-time RT-PCR. The mRNA levels of cerebellar BDNF in maternally separated rats were increased on PND16, while the other variables showed no significant alterations at any of the time points examined. However, the effects of an identical maternal separation on the cerebral cortex were previously reported to be completely different. These results indicate regional differences in the responses of neurotrophic factor ligands/receptors between the cerebellum and cerebral cortex. Given that neurotrophic factors play important roles in brain development, alterations in these factors may interrupt normal brain development and ultimately, lead to functional disruptions.

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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].…”

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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Neonatal repetitive maternal separation causes long-lasting alterations in various neurotrophic factor expression in the cerebral cortex of rats

Cited by 28 publications

References 67 publications

Microbiota and host determinants of behavioural phenotype in maternally separated mice

Microbiota and host determinants of behavioural phenotype in maternally separated mice

Differential effects of neonatal maternal separation on the expression of neurotrophic factors in rat brain. II: Regional differences in the cerebellum versus the cerebral cortex

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

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