Abnormal differentiation of dopaminergic neurons in zebrafish trpm7 mutant larvae impairs development of the motor pattern

Decker, Amanda R.; McNeill, Matthew; Lambert, Aaron; Overton, Jeffrey D.; Chen, Yu‐Chia; Lorca, Ramón A.; Johnson, Noel T.; Brockerhoff, Susan E.; Mohapatra, Durga P.; Macarthur, Heather; Panula, Pertti; Masino, Mark A.; Runnels, Loren W.; Cornell, Robert A.

doi:10.1016/j.ydbio.2013.11.015

Cited by 37 publications

(27 citation statements)

References 72 publications

(109 reference statements)

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“…In comparison to control tadpoles that swam away immediately when touched, some Mg 2+ deficient tadpoles twitched and swam away abnormally slow. This touch response defect was of our particular interest because TRPM7 mutant zebrafish lines have been shown to also exhibit movement defects (Decker et al , 2014, Low et al , 2011). In wild type zebrafish, a light-to-dark transition stimulates swimming behavior.…”

Section: Magnesium Homeostasis and Neurodegenerative Diseasesmentioning

confidence: 99%

TRPM channels and magnesium in early embryonic development

Komiya¹,

Runnels²

2015

Int. J. Dev. Biol.

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Magnesium (Mg2+) is the second most abundant cellular cation and is essential for all stages of life, from the early embryo to adult. Mg2+ deficiency causes or contributes to many human diseases, including migraine headaches, Parkinson’s disease, Alzheimer’s disease, hypotension, type 2 diabetes mellitus and cardiac arrhythmias. Although the concentration of Mg2+ in the extracellular environment can vary significantly, the total intracellular Mg2+ concentration is actively maintained within a relatively narrow range (14 – 20 mM) via tight, yet poorly understood, regulation of intracellular Mg2+ by Mg2+ transporters and Mg2+-permeant ion channels. Recent studies have continued to add to the growing number of Mg2+ transporters and ion channels involved in Mg2+ homeostasis, including TRPM6 and TRPM7, members of the transient receptor potential (TRP) ion channel family. Mutations in TRPM6, including amino acid substitutions that prevent its heterooligomerization with TRPM7, occur in the rare autosomal-recessive disease hypomagnesemia with secondary hypocalcemia (HSH). However, is the fact that genetic ablation of either gene in mice results in early embryonic lethality that has raised the question of whether these channels’ capacity to mediate Mg2+ influx plays an important role in embryonic development. Here we review what is known of the function of Mg2+ in early development and summarize recent findings regarding the function of the TRPM6 and TRPM7 ion channels during embryogenesis.

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Section: Magnesium Homeostasis and Neurodegenerative Diseasesmentioning

confidence: 99%

TRPM channels and magnesium in early embryonic development

Komiya¹,

Runnels²

2015

Int. J. Dev. Biol.

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“…Similarly, rats that were exposed to restricted intake of Ca 2+ and/or Mg 2+ over two generations resulted in severe loss of DA neurons [13]. In addition, mutations in TRPM7 also resulted in a defect in DA neurons in zebrafish models [23]. Together, these studies suggest that Mg 2+ homeostasis via TRPM7 could play a key role in neuronal function [24].…”

Section: Introductionmentioning

confidence: 97%

Magnesium-Induced Cell Survival Is Dependent on TRPM7 Expression and Function

2019

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Mg 2+ homeostasis is essential for cell survival and the loss of this regulation has been associated with many neurodegenerative diseases, including loss of dopaminergic neurons. Although the neurotoxin-mediated loss of dopaminergic neurons in Parkinson disease models is extensively studied, the ion channel(s) that regulate Mg 2+ homeostasis and thus could prevent neuronal cell death is not yet identified. Here, we show that TRPM7 (transient receptor potential melastatin 7) is involved in regulating Mg 2+ homeostasis in dopaminergic cells. Importantly, transient loss of TRPM7 decreased intracellular Mg 2+ levels and decreased dopaminergic cells/neurons survival. We provide further evidence that both increases in extracellular Mg 2+ or transiently increasing TRPM7 levels protected dopaminergic SH-SY5Y cells against neurotoxin-mediated cell death. Neurotoxin treatment significantly decreased TRPM7 levels in both SH-SY5Y cells and the substantia nigra pars compacta region of mice, along with a decrease in Mg 2+ influx. Moreover, Mg 2+ supplementation showed a concentration-dependent decrease in caspase-3 activity, an increase in cell survival, restored mitochondrial membrane potential, and increase TRPM7 levels in neurotoxin-treated cells. In contrast, transient silencing of TRPM7 inhibited the positive effect of Mg 2+ supplementation in protecting against neurotoxins. Whereas, TRPM7 overexpression not only maintained Mg 2+ homeostasis but also inhibited caspase 3 activity that induced cell survival. Overall, these results suggest a significant role of TRPM7 channels in Mg 2+ homeostasis and the survival of neurotoxininduced loss of dopaminergic cells.

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“…Continuous administration of Mg 2+ significantly inhibited the neurotoxicity of MPP + , reduced the death of dopaminergic neurons, and improved the length of dopaminergic neurites (Hashimoto et al, 2008). In a recent zebrafish study, TRPM7 mutation suppressed dopamine-dependent developmental transitions and increased sensitivity to the neurotoxicity of MPP + (Decker et al, 2014), and expression of the channel-dead variant of TRPM7 in SH-SY5Y cells increased cell death. These studies suggest that the role of Mg 2+ influx and TRPM7 in dopaminergic neurons is important and could be a therapeutic target for PD.…”

Section: Trpm7mentioning

confidence: 94%

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

et al. 2020

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The development of treatment for neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is facing medical challenges due to the increasingly aging population. However, some pharmaceutical companies have ceased the development of therapeutics for NDs, and no new treatments for NDs have been established during the last decade. The relationship between ND pathogenesis and risk factors has not been completely elucidated. Herein, we review the potential involvement of transient receptor potential (TRP) channels in NDs, where oxidative stress and disrupted Ca 2+ homeostasis consequently lead to neuronal apoptosis. Reactive oxygen species (ROS) -sensitive TRP channels can be key risk factors as polymodal sensors, since progressive late onset with secondary pathological damage after initial toxic insult is one of the typical characteristics of NDs. Recent evidence indicates that the dysregulation of TRP channels is a missing link between disruption of Ca 2+ homeostasis and neuronal loss in NDs. In this review, we discuss the latest findings regarding TRP channels to provide insights into the research and quests for alternative therapeutic candidates for NDs. As the structures of TRP channels have recently been revealed by cryo-electron microscopy, it is necessary to develop new TRP channel antagonists and reevaluate existing drugs.

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Abnormal differentiation of dopaminergic neurons in zebrafish trpm7 mutant larvae impairs development of the motor pattern

Cited by 37 publications

References 72 publications

TRPM channels and magnesium in early embryonic development

TRPM channels and magnesium in early embryonic development

Magnesium-Induced Cell Survival Is Dependent on TRPM7 Expression and Function

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

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