Interplay of glia activation and oxidative stress formation in fluoride and aluminium exposure

Akinrinade, Ibukun; Memudu, Adejoke Elizabeth; Ogundele, Olalekan Michael; Ajetunmobi, Olanrewaju I

doi:10.1016/j.pathophys.2014.12.001

Cited by 45 publications

(43 citation statements)

References 32 publications

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“…Recently, it is reported that increases of microglia activation and inflammatory response were seen in aluminum, fluoride, and a combination of aluminum-fluoride-treated rat brain [23]. Microglia are the resident immune cell population of the CNS and are highly sensitive to physiological and pathological changes.…”

Section: Effects Of Fluoride On the Inflammatory Factor Expressions Imentioning

confidence: 99%

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Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Yan

Liu

et al. 2015

Mol Neurobiol

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Excessive exposure to fluoride results in structural and functional damages to the central nervous system (CNS), and neurotoxicity of fluoride may be associated with neurodegenerative changes. Chronic microglial activation appears to cause neuronal damage through producing proinflammatory cytokines and is involved in many neurodegenerative disorders. It is not known about effects on microglia of fluoride. In the present study, healthy adult Wistar rats were exposed to 60 and 120 ppm fluoride in drinking water for 10 weeks, and control rats received deionized water. After 10 weeks, rats were sacrificed under anesthesia then apoptosis in neuron and inflammatory factors secreted by microglia were determined. We found that apoptosis of neurons in fluoride-treated rat brain increased and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive immunofluorescence increased with increasing fluoride concentrations. Bax protein expression increased and Bcl-2 protein expression decreased in fluoride-treated rat brain compared with that of the control rat brain. The microglia in the hippocampus and cortex of fluoride-treated rats were activated by immunostaining with OX-42, a marker of activated microglia, and OX-42-positive microglia cells were more abundant in the hippocampus than in the cortex. The levels of IL-1β and IL-6 protein expression in OX-42-labeled microglial cells were significantly increased in the cortex and hippocampus of rats exposed to fluoride, and TNF-α immunoreactivity in microglial cells of the hippocampus was significantly higher in the 120 ppm fluoride-treated group than that in the control group. Our results indicate that fluoride induced neuron apoptosis and expressions of inflammatory factors by activating microglia in rat brain.

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Section: Effects Of Fluoride On the Inflammatory Factor Expressions Imentioning

confidence: 99%

“…In addition, glial activation and inflammatory response were seen and a close link between oxidative stress neuroinflammation and degeneration in aluminum-fluoride toxicity rats was observed. Microglial cells were activated during fluoride-and aluminum-induced neuronal damage [23].…”

Section: Introductionmentioning

confidence: 99%

Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Yan

Liu

et al. 2015

Mol Neurobiol

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“…In this regard, microglial cells have been extensively studied as the primary effectors of inflammatory responses in the central nervous system after a brain aggression; however, various reports have shown that astrocytes, the most abundant glial cells that contribute to the blood brain barrier architecture and function, are the first cells to respond to a toxic challenge and induce microglia recruitment through different chemokines production [40,41].…”

Section: Discussionmentioning

confidence: 99%

Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMAIII) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression

et al. 2016

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Long-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells.Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain. We propose that iAs could induce cognitive impairment through inflammatory response activation in astrocytes. In the present work, rat cortical astrocytes were acutely exposed in vitro to the monomethylated metabolite of iAs (MMA III ), which accumulates in glial cells without compromising cell viability. MMA III LD 50 in astrocytes was 10.52 μM, however, exposure to sub-toxic MMA III concentrations (50 to 1000 nM) significantly increased IL-1β, IL-6, TNF-α, COX-2, and MIF-1 gene expression. These effects were consistent with amyloid precursor protein (APP) and β-secretase (BACE-1) increased gene expression, mainly for those MMA III concentrations that also induced TNF-α over-expression. Other effects of MMA III on cortical astrocytes included increased proliferative and metabolic activity. All tested MMA III concentrations led to an inhibition of intracellular lactate dehydrogenase (LDH) activity. Results suggest that MMA III induces important metabolic and functional changes in astrocytes that may affect brain homeostasis and that inflammation may play a major role in cognitive impairment-related pathogenicity in As-exposed populations.

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“…GFAP is a widely used marker of astrocyte activation, which is closely linked to oxidative stress (Akinrinade, Memudu, Ogundele, & Ajetunmobi, ) and neuroinflammation (Heneka et al, ), two phenomena that occur in neurodegenerative diseases such as AD. It is well established that activated astrocytes cluster around plaques (Hadley et al, ; Perez et al, ; Rodriguez‐Arellano, Parpura, Zorec, & Verkhratsky, ; Thomason, Smithson, Hazrati, McLaurin, & Kawaja, ).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a 3xTg‐AD mouse model of Alzheimer's disease with the senescence accelerated mouse prone 8 (SAMP8) background

Virgili

Lebbadi

Tremblay

et al. 2018

Synapse

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No model fully recapitulates the neuropathology of Alzheimer's disease (AD). Although the triple-transgenic mouse model of AD (3xTg-AD) expresses Aβ plaques and tau-laden neurofibrillary tangles, as well as synaptic and behavioral deficits, it does not display frank neuronal loss. Because old age is the most important risk factor in AD, senescence-related interactions might be lacking to truly establish an AD-like environment. To investigate this hypothesis, we bred the 3xTg-AD mouse with the senescence-accelerated mouse prone 8 (SAMP8), a model of accelerated aging. We generated four groups of heterozygous mice with either the SAMP8 or SAMR1 (senescence-resistant-1) genotype, along with either the 3xTg-AD or non-transgenic (NonTg) genotype. Despite no differences among groups in total latency to escape the Barnes maze, a greater number of errors were noticed before entering the target hole in 19-month-old P8/3xTg-AD mice at day 5, compared to other groups. Postmortem analyses revealed increased cortical levels of phospho-tau (Thr231) in female P8/3xTg-AD mice (+277% vs. R1/3xTg-AD mice), without other tau-related changes. Female P8/3xTg-AD mice exhibited higher cortical soluble Aβ40 and Aβ42 concentrations (Aβ40, +85%; Aβ42, +35% vs. R1/3xTg-AD), whereas insoluble forms remained unchanged. Higher Aβ42 load coincided with increased astroglial activation in female P8/3xTg-AD mice, as measured with glial fibrillary acidic protein (GFAP) (+57% vs. R1/3xTg-AD mice). To probe neuronal degeneration, concentrations of neuronal nuclei (NeuN) were measured, but no differences were detected between groups. Altogether, the SAMP8 genotype had deleterious effects on spatial memory and exerted female-specific aggravation of AD neuropathology without overt neurodegeneration in 3xTg-AD mice.

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Interplay of glia activation and oxidative stress formation in fluoride and aluminium exposure

Cited by 45 publications

References 32 publications

Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMAIII) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression

Characterization of a 3xTg‐AD mouse model of Alzheimer's disease with the senescence accelerated mouse prone 8 (SAMP8) background

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