Neurotoxicity of Metal Mixtures

Advances in neurobiology, Год журнала: 2017, Номер unknown, С. 227 - 265

Опубликована: Янв. 1, 2017

Язык: Английский

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Parkinson's Disease and Neurodegeneration: GABA-Collapse Hypothesis

Frontiers in Neuroscience, Год журнала: 2016, Номер 10

Опубликована: Июнь 9, 2016

Neurodegenerative diseases constitute a heterogeneous group of age-related disorders that are characterized by slow but irreversible deterioration brain functions. Evidence accumulated over more than two decades has implicated calcium-related homeostatic mechanisms, giving rise to the Ca2+ hypothesis aging and, ultimately, cell death. Gamma-aminobutyric acid (GABA) is main inhibitory neurotransmitter within central (CNS), peripheral and enteric nervous systems. It appears be involved in wide variety physiological functions outside system, maintained through complex interaction between GABA calcium-dependent neurotransmission cellular metabolic Within CNS Ca2+/GABA mechanism stabilizes neuronal activity both at systemic levels. Decline Ca2 +/GABA control initiates several cascading processes leading weakened protective barriers (in particular blood-brain barrier) accumulations intracellular deposits calcium Lewy bodies. Linking such vital synaptic transmission with metabolism (both tissue level) means common reciprocal inhibition results fragile balance, which prone destabilization auto-destruction. The decline etiology proposed here apply all human neurodegenerative initiated abnormal Therefore, original description Parkinson's disease (PD) as due selective damage dopaminergic neurons mesencephalon should updated into concept severe multisystemic disorder whose clinical symptoms reflect localization progression most advanced pathology. A future complete therapeutic approach PD aimed first slowing (or stopping) functional decline.

Язык: Английский

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Redox dynamics of manganese as a mitochondrial life-death switch

Biochemical and Biophysical Research Communications, Год журнала: 2017, Номер 482(3), С. 388 - 398

Опубликована: Янв. 1, 2017

Язык: Английский

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Manganese exposure induces neuroinflammation by impairing mitochondrial dynamics in astrocytes

NeuroToxicology, Год журнала: 2017, Номер 64, С. 204 - 218

Опубликована: Май 21, 2017

Chronic manganese (Mn) exposure induces neurotoxicity, which is characterized by Parkinsonian symptoms resulting from impairment in the extrapyramidal motor system of basal ganglia. Mitochondrial dysfunction and oxidative stress are considered key pathophysiological features Mn neurotoxicity. Recent evidence suggests astrocytes as a major target neurotoxicity since accumulates predominantly astrocytes. However, primary mechanisms underlying Mn-induced astroglial its role metal not completely understood. In this study, we examined interrelationship between mitochondrial astrocytic inflammation We first evaluated whether alters bioenergetics cultured Metabolic activity assessed MTS assay revealed an IC50 92.68μM at 24h mouse (PMAs) 50.46μM human U373 cell line. treatment reduced mass, indicative impaired function biogenesis, was substantiated significant reduction mRNA mitofusin-2, protein that serves ubiquitination for mitophagy. Furthermore, increased circularity indicating augmented fission. Seahorse analysis status Mn-treated significantly oxygen consumption rate well ATP-linked respiration rate. The effect on energy deficits further supported ATP production. Mn-exposed also exhibited severely quiescent phenotype, inability oligomycin to increase extracellular acidification Since regulate immune functions CNS, modulates inflammation. only stimulated release proinflammatory cytokines, but exacerbated inflammatory response induced aggregated α-synuclein. novel mitochondria-targeted antioxidant, mito-apocynin, attenuated gene expression, supporting mitochondria mediating astrogliosis. Lastly, intranasal delivery vivo elevated GFAP depressed TH levels olfactory bulbs, clearly involvement dopaminergic Collectively, our study demonstrates drives events impairing bioenergetics.

Язык: Английский

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The effects of manganese overexposure on brain health

Neurochemistry International, Год журнала: 2020, Номер 135, С. 104688 - 104688

Опубликована: Янв. 20, 2020

Язык: Английский

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