BDNF and Huntingtin protein modifications by manganese: implications for striatal medium spiny neuron pathology in manganese neurotoxicity

Stansfield, Kirstie H.; Bichell, Terry Jo; Bowman, Aaron B.; Guilarte, Tomás R.

doi:10.1111/jnc.12926

Cited by 19 publications

(9 citation statements)

References 60 publications

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“…It is therefore possible that Mn may interact with brain-derived neurotrophic factor (BDNF), because BNDF plays a pivotal role in regulating the dendrite development and subsequent structural and functional synaptic plasticity in HDG (Alderson et al, 1990;Cohen-Cory et al, 2010;Horch and Katz, 2002;Gorski et al, 2003;Tolwani et al, 2002;Vigers et al, 2012;Wang et al, 2015). Recent studies in rodents, nonhuman primates, and human workers have also demonstrated a decreased BDNF level in the striatum, hippocampus, and plasma following Mn exposure (Liang et al, 2015;Lv et al, 2014;Stansfield et al, 2014;Sumanont et al, 2007;Zou et al, 2014). Thus, in-depth studies are necessary to further evaluate whether and to what degree Mn exposure may alter the dendritic formation in adult brain and how BDNF may contribute to Mn action.…”

Section: Discussionmentioning

confidence: 99%

Subchronic Manganese Exposure Impairs Neurogenesis in the Adult Rat Hippocampus

Adamson¹,

Shen²,

Jiang³

et al. 2018

Toxicological Sciences

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Adult neurogenesis takes place in the brain subventricular zone (SVZ) in the lateral walls of lateral ventricles and subgranular zone (SGZ) in the hippocampal dentate gyrus (HDG), and functions to supply newborn neurons for normal brain functionality. Subchronic Mn exposure is known to disrupt adult neurogenesis in the SVZ. This study was designed to determine whether Mn exposure disturbed neurogenesis within the adult HDG. Adult rats (10 weeks old) received a single dose of bromodeoxyuridine (BrdU) at the end of 4-week Mn exposure to label the proliferating cells. Immunostaining and cell counting data showed that BrdU(+) cells in Mn-exposed HDG were about 37% lower than that in the control (p < .05). The majority of BrdU(+) cells were identified as Sox2(+) cells. Another set of adult rats received BrdU injections for 3 consecutive days followed by 2- or 4-week Mn exposure to trace the fate of BrdU-labeled cells in the HDG. The time course studies indicated that Mn exposure significantly reduced the survival rate (54% at 2 weeks and 33% at 4 weeks), as compared with that in the control (80% at 2 weeks and 51% at 4 weeks) (p < .01). A significant time-dependent migration of newborn cells from the SGZ toward the granule cell layer was also observed in both control and Mn-exposed HDG. Triple-stained neuroblasts and mature neurons further revealed that Mn exposure significantly inhibited the differentiation of immature neuroblasts into mature neurons in the HDG. Taken together, these observations suggest that subchronic Mn exposure results in a reduced cell proliferation, diminished survival of adult-born neurons, and inhibited overall neurogenesis in the adult HDG. Impaired adult neurogenesis is likely one of the mechanisms contribute to Mn-induced Parkinsonian disorder.

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Section: Discussionmentioning

confidence: 99%

Subchronic Manganese Exposure Impairs Neurogenesis in the Adult Rat Hippocampus

Adamson¹,

Shen²,

Jiang³

et al. 2018

Toxicological Sciences

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“…In a study examining the effects of manganese exposure with HT disease pathology, manganese exposure adversely affects medium spiny neuron dendritic length and spine density which is associated with a decrease brain-derived neurotrophic factor which caused alterations in the Htt gene which causes HT [250]. In study using a monkey model, exposure to manganese was shown to promote α-synuclein positive cells, which indicate the development of PD and dementia [251].…”

Section: Mechanisms Of Actions Of Estrogenic Endocrine Disruptors mentioning

confidence: 99%

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

Preciados

Yoo

Roy

2016

IJMS

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During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1) signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2) and NRF1. Some of these genes are involved with brain diseases, such as Alzheimer’s Disease (AD), Parkinson’s Disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis, Autism Spectrum Disorder, and Brain Neoplasms. For example, the search of enriched pathways showed that top ten E2 interacting genes in AD—APOE, APP, ATP5A1, CALM1, CASP3, GSK3B, IL1B, MAPT, PSEN2 and TNF—underlie the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) AD pathway. With AD, the six E2-responsive genes are NRF1 target genes: APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1. These genes are also responsive to the following EEDs: ethinyl estradiol (APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1), BPA (APBB2, EIF2S1, ENO1, MAPT, and PAXIP1), dibutyl phthalate (DPYSL2, EIF2S1, and ENO1), diethylhexyl phthalate (DPYSL2 and MAPT). To validate findings from Comparative Toxicogenomics Database (CTD) curated data, we used Bayesian network (BN) analysis on microarray data of AD patients. We observed that both gender and NRF1 were associated with AD. The female NRF1 gene network is completely ...

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“…Manganism is a syndrome similar to Parkinson’s disease (PD), characterized by psychiatric and cognitive deficits and motor impairment [27, 28]. Mn is also a putative environmental modifier of Huntington’s disease (HD) [29–31]. The symptoms caused by the accumulation of Mn include dystonia, bradykinesia and rigidity due to damage to dopaminergic (DAergic) neurons and gliosis [12, 32].…”

Section: Introductionmentioning

confidence: 99%

“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

Peres

Schettinger

Chen

et al. 2016

BMC Pharmacol Toxicol

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280

183

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Manganese (Mn) is an essential heavy metal. However, Mn’s nutritional aspects are paralleled by its role as a neurotoxicant upon excessive exposure. In this review, we covered recent advances in identifying mechanisms of Mn uptake and its molecular actions in the brain as well as promising neuroprotective strategies. The authors focused on reporting findings regarding Mn transport mechanisms, Mn effects on cholinergic system, behavioral alterations induced by Mn exposure and studies of neuroprotective strategies against Mn intoxication. We report that exposure to Mn may arise from environmental sources, occupational settings, food, total parenteral nutrition (TPN), methcathinone drug abuse or even genetic factors, such as mutation in the transporter SLC30A10. Accumulation of Mn occurs mainly in the basal ganglia and leads to a syndrome called manganism, whose symptoms of cognitive dysfunction and motor impairment resemble Parkinson’s disease (PD). Various neurotransmitter systems may be impaired due to Mn, especially dopaminergic, but also cholinergic and GABAergic. Several proteins have been identified to transport Mn, including divalent metal tranporter-1 (DMT-1), SLC30A10, transferrin and ferroportin and allow its accumulation in the central nervous system. Parallel to identification of Mn neurotoxic properties, neuroprotective strategies have been reported, and these include endogenous antioxidants (for instance, vitamin E), plant extracts (complex mixtures containing polyphenols and non-characterized components), iron chelating agents, precursors of glutathione (GSH), and synthetic compounds that can experimentally afford protection against Mn-induced neurotoxicity.

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BDNF and Huntingtin protein modifications by manganese: implications for striatal medium spiny neuron pathology in manganese neurotoxicity

Cited by 19 publications

References 60 publications

Subchronic Manganese Exposure Impairs Neurogenesis in the Adult Rat Hippocampus

Subchronic Manganese Exposure Impairs Neurogenesis in the Adult Rat Hippocampus

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

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