Zinc deficiency impairs neuronal precursor cell proliferation and induces apoptosis via p53-mediated mechanisms

Corniola, Rikki S.; Tassabehji, Nadine M.; Hare, Joan; Sharma, Girdhari M.; Levenson, Cathy W.

doi:10.1016/j.brainres.2008.08.040

Cited by 143 publications

(136 citation statements)

References 43 publications

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“…This is consistent with previous works showing that zinc deficiency is capable of inducing apoptosis both in vitro and in vivo (Jankowski-Hennig et al, 2000;Duffy et al, 2001;Corniola et al, 2008). TrkB is a membrane receptor, and activation of TrkB can trigger the ERK pathway (Klesse and Parada, 1999;Kaplan and Miller, 2000), which plays an important role in neuronal survival (Chao, 2003).…”

Section: Discussionsupporting

confidence: 92%

Lactational zinc deficiency‐induced hippocampal neuronal apoptosis by a BDNF‐independent TrkB signaling pathway

Gao

Zheng

et al. 2011

Hippocampus

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It is well-known that zinc deficiency leads to neuronal death in the brain. Here we tested the hypothesis that changes in the TrkB signaling pathway are involved in hippocampal neuronal apoptosis of suckling offspring with maternal zinc deficiency. Postpartum mice were fed a zinc-deficient (0.85 ppm) diet and their offspring were used as a lactational zinc deficiency mouse model. At P7, P14, and P21, changes in hippocampal neuronal apoptosis were assessed by Nissl and TUNEL staining. BDNF levels and TrkB neurotrophic signaling were examined using immunoblotting assay. Lactational zinc deficiency resulted in lower levels of p-TrkB and p-ERK, and higher levels of Bax/Bcl-2 and caspase-3 in the hippocampus, suggesting that zinc deficiency-induced low levels of TrkB phosphorylation would abrogate the downstream ERK signaling pathway, leading to hippocampal neuronal apoptosis. Most interestingly, our data showed that the activity of Src, a key molecule for zinc-induced TrkB activation through the BDNF-independent pathway, was inhibited significantly, and the expression levels of BDNF were significantly increased in the hippocampus of suckling mice. The present data indicate that zinc depletion-induced hippocampal neuronal apoptosis is likely through modulation of the TrkB neurotrophic signaling pathway by a BDNF-independent and Src-dependent mechanism, whereas higher expression of BDNF is considered as a protective response, which cannot fully compensate for the injury caused by maternal zinc deficiency.

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Section: Discussionsupporting

confidence: 92%

Lactational zinc deficiency‐induced hippocampal neuronal apoptosis by a BDNF‐independent TrkB signaling pathway

Gao

Zheng

et al. 2011

Hippocampus

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“…The tumor-suppressor protein p53 is involved in the detection and repair of DNA damage and its DNA-binding region contains zinc. Depending on the duration of the zinc deficiency, p53 can cause cell cycle arrest to allow DNA repair, or trigger apoptosis in response to DNA damage (Corniola et al, 2008). In zinc-deficient cells, p53 protein expression is increased.…”

Section: Oxidative Stress and Damagementioning

confidence: 99%

Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal development

Uriu‐Adams

Keen

2010

Birth Defects Research Pt B

118

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A large body of evidence supports the concept that human pregnancy outcome is significantly influenced by the nutritional status of the mother. The consumption of "poor diets" has been associated with an increased risk for pregnancy complications, including gross structural birth defects, prematurity, low birth weight, and an increased risk for neurobehavioral and immunological abnormalities after birth. Forty-four years ago, zinc deficiency in mammals was shown to be teratogenic. Maternal zinc deficiency produces effects ranging from infertility and embryo/fetal death, to intrauterine growth retardation and teratogenesis. Postnatal complications of maternal zinc deficiency can also occur, and include behavioral abnormalities, impaired immunocompetence, and an elevated risk for high blood pressure in the offspring. It has been suggested that developmental zinc deficiency in humans can present a significant challenge to the conceptus, increasing the risk for numerous defects. Developmental zinc deficiency can occur through multiple pathways, and the concept that acute phase response-induced changes in maternal zinc metabolism may be a common cause of embryonic and fetal zinc deficiency is presented. Potential mechanisms underlying the teratogenic effects of zinc deficiency are reviewed. The potential value of maternal zinc supplementation in high risk pregnancies is discussed.

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“…Interestingly Williams et al [122] have also identified BDNF as a potential mediator of the effect of flavonoids on cognition. Deficiency in zinc inhibits AHN [14] and induces depression in rodents [110], whereas independent intervention studies have shown the efficacy of zinc supplements in improving symptoms of depression (for review [108]). Corniola et al [14] hypothesized that zinc plays a role in AHN by regulating p53-dependent molecular mechanisms that control neuronal precursor cell proliferation and survival.…”

Section: Dietary Modulation Of Adult Hippocampal Neurogenesismentioning

confidence: 99%

“…However, neurons induced in response to supra-physiological levels of caffeine have a lower survival rate than control cells and increased proliferation does not yield an increase in AHN [121]. Curcumin is a natural phenolic component of yellow curry spice that increases AHN in rodents [53] and epidemiological studies have reported better cognitive performance from curry Mouse Increased survival [62], [61], [54], [8] Omega 3 fatty acids Rat Increased (DHA) [46] Flavonoids Rat, chronically stressed Increased proliferation [3] Blueberry Rat Increased proliferation [12] Curcumin low concentrations Mouse Increased proliferation [53] Retinoic acid excess Mouse Decreased proliferation [16] Vitamin A deficiency Rat Decreased proliferation (rescued with retinoic acid) [9] Thiamine deficiency Mouse Decreased proliferation/survival [128] Zinc deficiency Rat male Decreased proliferation/survival [14] Folate consumption in ageing populations [83]. Moreover, in vitro studies have shown that curcumin exerted biphasic effects on progenitor cells; low concentrations stimulated cell proliferation, whereas high concentrations were cytotoxic.…”

Section: Dietary Modulation Of Adult Hippocampal Neurogenesismentioning

confidence: 99%

Impact of diet on adult hippocampal neurogenesis

2009

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Research over the last 5 years has firmly established that learning and memory abilities, as well as mood, can be influenced by diet, although the mechanisms by which diet modulates mental health are not well understood. One of the brain structures associated with learning and memory, as well as mood, is the hippocampus. Interestingly, the hippocampus is one of the two structures in the adult brain where the formation of newborn neurons, or neurogenesis, persists. The level of neurogenesis in the adult hippocampus has been linked directly to cognition and mood. Therefore, modulation of adult hippocampal neurogenesis (AHN) by diet emerges as a possible mechanism by which nutrition impacts on mental health. In this study, we give an overview of the mechanisms and functional implications of AHN and summarize recent findings regarding the modulation of AHN by diet.

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Zinc deficiency impairs neuronal precursor cell proliferation and induces apoptosis via p53-mediated mechanisms

Cited by 143 publications

References 43 publications

Lactational zinc deficiency‐induced hippocampal neuronal apoptosis by a BDNF‐independent TrkB signaling pathway

Lactational zinc deficiency‐induced hippocampal neuronal apoptosis by a BDNF‐independent TrkB signaling pathway

Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal development

Impact of diet on adult hippocampal neurogenesis

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