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

Xu, He; Gao, Huiling; Zheng, Wei; Xin, Na; Chen, Zhihong; Bai, Shuling; Wang, Zhan-You

doi:10.1002/hipo.20767

Cited by 25 publications

(13 citation statements)

References 35 publications

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“…Furthermore, zinc also functions as an agonist for TrkB and potentiates LTP of CA3 synapses in hippocampal mossy fibers (134). Concerning cell survival, it has been reported that increased apoptotic cell death in hippocampal regions (including CA1, CA3, and dentate gyrus) and decreased phosphorylation of hippocampal TrkB and ERK were observed in lactating zinc deficient (0.85 ppm) mice (135). Importantly, a zinc deficient diet (0.2 and 1 ppm) for 3 and 6 weeks caused depressive and anxiety-like behaviors in addition to anhedonia (136–138), while these depressive-like behaviors were reversed after chronic treatment with typical antidepressants (such as fluoxetine, imipramine, and reboxetine) (136, 138).…”

Section: Action Of Zinc In Depressionmentioning

confidence: 99%

The Role of Brain-Derived Neurotrophic Factor in Comorbid Depression: Possible Linkage with Steroid Hormones, Cytokines, and Nutrition

et al. 2014

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Increasing evidence demonstrates a connection between growth factor function (including brain-derived neurotrophic factor, BDNF), glucocorticoid levels (one of the steroid hormones), and the pathophysiology of depressive disorders. Because both BDNF and glucocorticoids regulate synaptic function in the central nervous system, their functional interaction is of major concern. Interestingly, alterations in levels of estrogen, another steroid hormone, may play a role in depressive-like behavior in postpartum females with fluctuations of BDNF-related molecules in the brain. BDNF and cytokines, which are protein regulators of inflammation, stimulate multiple intracellular signaling cascades involved in neuropsychiatric illness. Pro-inflammatory cytokines may increase vulnerability to depressive symptoms, such as the increased risk observed in patients with cancer and/or autoimmune diseases. In this review, we discuss the possible relationship between inflammation and depression, in addition to the cross-talk among cytokines, BDNF, and steroids. Further, since nutritional status has been shown to affect critical pathways involved in depression through both BDNF function and the monoamine system, we also review current evidence surrounding diet and supplementation (e.g., flavonoids) on BDNF-mediated brain functions.

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Section: Action Of Zinc In Depressionmentioning

confidence: 99%

The Role of Brain-Derived Neurotrophic Factor in Comorbid Depression: Possible Linkage with Steroid Hormones, Cytokines, and Nutrition

et al. 2014

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“…Severe zinc deficiency imposed to adult rats or mice decreases neural progenitor cell proliferation in the dentate gyrus of the hippocampus (Corniola et al 2008; Suh et al 2009). Severe zinc deficiency both during lactation and during adulthood has been shown to increase hippocampal apoptosis (Gao et al 2009; Xu et al 2011). Culture in zinc deficient media decreases the proliferation of IMR-32 neuroblastoma cells, causing an arrest of the cell cycle at the G0/G1 phase and the induction of apoptosis (Adamo et al 2010).…”

Section: Zinc and Brain Developmentmentioning

confidence: 99%

Zinc and the ERK Kinases in the Developing Brain

Nuttall

Oteiza

2011

Neurotox Res

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This article reviews evidence in support of the hypothesis that impaired activation of the extracellular signal-regulated kinases (ERK1/2) contributes to the disruptions in neurodevelopment associated with zinc deficiency. These kinases are implicated in major events of brain development, including proliferation of progenitor cells, neuronal migration, differentiation, and apoptotic cell death. In humans, mutations in ERK1/2 genes have been associated with neuro-cardio-facial-cutaneous syndromes. ERK1/2 deficits in mice have revealed impaired neurogenesis, altered cellularity, and behavioral abnormalities. Zinc is an important modulator of ERK1/2 signaling. Conditions of both zinc deficiency and excess affect ERK1/2 phosphorylation in fetal and adult brains. Hypophosphorylation of ERK1/2, associated with decreased zinc availability in cell cultures, is accompanied by decreased proliferation and an arrest of the cell cycle at the G0/G1 phase. Zinc and ERK1/2 have both been shown to modulate neural progenitor cell proliferation and cell death in the brain. Furthermore, behavioral deficits resulting from developmental zinc deficiency are similar to those observed in mice with decreased ERK1/2 signaling. For example, impaired performance on behavioral tests of learning and memory; such as the Morris water maze, fear conditioning, and the radial arm maze; has been reported in both animals exposed to developmental zinc deficiency and transgenic mice with decreased ERK signaling. Future study should clarify the mechanisms through which a dysregulation of ERK1/2 may contribute to altered brain development associated with dietary zinc deficiency and with conditions that limit zinc availability.

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“…In fact, the independent actions of Src and BDNF have been reported in the past as a response to a dietary imbalance caused by zinc deficiency [88].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis of the Effects of a Fish Oil Enriched Diet on Murine Brains

et al. 2014

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The health benefits of fish oil enriched with high omega-3 polyunsaturated fatty acids (n-3 PUFA) are widely documented. Fish oil as dietary supplements, however, show moderate clinical efficacy, highlighting an immediate scope of systematic in vitro feedback. Our transcriptomic study was designed to investigate the genomic shift of murine brains fed on fish oil enriched diets. A customized fish oil enriched diet (FD) and standard lab diet (SD) were separately administered to two randomly chosen populations of C57BL/6J mice from their weaning age until late adolescence. Statistical analysis mined 1,142 genes of interest (GOI) differentially altered in the hemibrains collected from the FD- and SD-fed mice at the age of five months. The majority of identified GOI (∼40%) encodes proteins located in the plasma membrane, suggesting that fish oil primarily facilitated the membrane-oriented biofunctions. FD potentially augmented the nervous system's development and functions by selectively stimulating the Src-mediated calcium-induced growth cascade and the downstream PI3K-AKT-PKC pathways. FD reduced the amyloidal burden, attenuated oxidative stress, and assisted in somatostatin activation—the signatures of attenuation of Alzheimer's disease, Parkinson's disease, and affective disorder. FD induced elevation of FKBP5 and suppression of BDNF, which are often linked with the improvement of anxiety disorder, depression, and post-traumatic stress disorder. Hence we anticipate efficacy of FD in treating illnesses such as depression that are typically triggered by the hypoactivities of dopaminergic, adrenergic, cholinergic, and GABAergic networks. Contrastingly, FD's efficacy could be compromised in treating illnesses such as bipolar disorder and schizophrenia, which are triggered by hyperactivities of the same set of neuromodulators. A more comprehensive investigation is recommended to elucidate the implications of fish oil on disease pathomechanisms, and the result-driven repositioning of fish oil utilization may revitalize its therapeutic efficacy.

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

Cited by 25 publications

References 35 publications

The Role of Brain-Derived Neurotrophic Factor in Comorbid Depression: Possible Linkage with Steroid Hormones, Cytokines, and Nutrition

The Role of Brain-Derived Neurotrophic Factor in Comorbid Depression: Possible Linkage with Steroid Hormones, Cytokines, and Nutrition

Zinc and the ERK Kinases in the Developing Brain

Transcriptomic Analysis of the Effects of a Fish Oil Enriched Diet on Murine Brains

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