Cholesterol deficiency increases the vulnerability of hippocampal glia in primary culture to glutamate-induced excitotoxicity

Chou, Yun-Chia; Lin, Shin-Bey; Tsai, Lien Hsin; Tsai, Hung-I; Lin, Chiao Mei

doi:10.1016/s0197-0186(03)00003-2

Cited by 29 publications

(24 citation statements)

References 76 publications

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“…Thus, changes in sterols levels may reflect neurodegenerative changes. Indeed, disruption of cholesterol and triglyceride balance can modify synapse integrity, 9 increase neuronal vulnerability to insults, 10 and may play roles in the pathogenesis of Alzheimer disease, ALS, and HIV-D. 2,11,12 The nervous system is particularly susceptible to the damaging effects of free radicals for several reasons. The brain contains high concentrations of polyunsaturated fatty acids that are susceptible to lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

Associative and predictive biomarkers of dementia in HIV-1–infected patients

Bandaru

McArthur²,

Sacktor³

et al. 2007

Neurology

109

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Background-Infection with HIV can result in a debilitating CNS disorder known as HIV dementia (HIV-D). Since the advent of highly active antiretroviral therapy (HAART), the incidence of HIV-D has declined, but the prevalence continues to increase. In this new era of HIV-D, traditional biomarkers such as CSF viral load and monocyte chemotactic protein 1 levels are less likely to be associated with dementia in patients on HAART and biomarkers that can predict HIV-D have not yet been identified.

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Section: Discussionmentioning

confidence: 99%

Associative and predictive biomarkers of dementia in HIV-1–infected patients

Bandaru

McArthur²,

Sacktor³

et al. 2007

Neurology

109

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“…Furthermore, cholesterol depletion is thought to increase the vulnerability of neurons to glutamate excitotoxicity [26]. All these data constitutes signs of brain lipid derangements.…”

Section: Discussionmentioning

confidence: 99%

Reyess Syndrome, Encephalopathy, Hyperammonemia and Acetyl Salicylic Acid Ingestion in a City Hospital of Buenos Aires, Argentina

Lemberg¹,

Fernández²,

Coll³

et al. 2009

CDS

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Twelve cases of Reye's syndrome are presented with different degrees of encephalopathy, hyperammonemia and hypoglycemia; associated to acetyl salicylic acid (ASA) ingestion. The aim of the present retrospective study was to describe our experience in selected patients with Reye's syndrome associated to the ASA ingestion and to underline the influence of hyperammonemia on Reye's encephalopathy. All the cases presented moderate hyperbilirubinemia, elevated alanine aminotransferase, aspartate aminotransferase with an average of 302+/-205 UI/L and 285+/-149 UI/L respectively. Arterial blood ammonia averaged 172.4+/-71.3 micromol/L and glycaemia averaged 35.2+/-17.0 mg/dl. A high mortality was found in our series (41.7%). Considering that encephalopathy is the leading syndrome in these cases, the influence of ammonia on brain tissue was described. Glutamate is an excitotoxic neurotransmitter, capable to produce neuron and astrocyte damage and apoptosis. The presence of ASA could cause the onset of the mitochondrial permeability transition and the mitochondrial swelling in the astrocyte, leading to hyperammonemia. In Reye's syndrome, hyperammonemia and perhaps the increase of glutamate are the leading factors in the mechanism of brain damage and encephalopathy. Aspirin must be carefully administrated and controlled by professionals. Furthermore, parents must be informed about the risks in the use of this drug in children.

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“…MβCD in particular, has been shown to be an effective vehicle for delivering hydrophobic substances to cells in culture (Christian et al, 1997). However, evaluation of toxic effects has been focused of attention of a number of recent studies (Schondfelder et al, 2006;Chou et al, 2003;Li et al, 2006). This study was undertaken to further evaluate MβCD and establish the levels that is nontoxic to NGFDPC12 cells.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, 0.2% MβCD toxicity in fibroblasts cell lines (Pfitzner et al, 2000) exhibit lactate dehydrogenase activity in media culture comparable to control. However, 1% concentrations of MβCD triggered a significant induction of cell death and apoptosis in human keratinocytes cell lines (Schonfelder et al, 2006) and 2 mM of MβCD increases the vulnerability of hippocampal glia cells to glutamate-induced excitotoxicity (Chou et al, 2003). It has been proposed that the variability of the toxic effects of CDs observed in different cell system studied is correlated with the concentration of cholesterol in the membrane.…”

Section: Discussionmentioning

confidence: 99%

Characterization of methyl-β-cyclodextrin toxicity in NGF-differentiated PC12 cell death

et al. 2007

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Cyclodextrins (CDs) are used to deliver hydrophobic molecules in aqueous environments. Methyl-β-cyclodextrin (MβCD), a member of this family of molecules, has been proposed to be a good carrier to deliver fatty acids to cells in culture. This report focuses on studying the in vitro effects of MβCD on nerve growth factor-differentiated PC12 (NGFDPC12) cells, a tissue culture model to study neuronal survival and differentiation. The main findings are: (1) NGFDPC12 cells have normal viability when exposed to 0.12% MβCD but showed a significant loss in cell viability at higher concentrations; (2) NGFDPC12 cells exposed to 0.25% MβCD exhibit nuclear condensation, blebbing and apoptotic bodies, and whole cell lysates exhibited an increase in caspase-3-like activity and high levels of Bax and Bcl-X L protein expression compared to control. Cultures treated with 0.25% MβCD also showed cleavage of normal 21-kDa Bax protein into a 18-kDa fragment. (3) Experiments using 0.12% MβCD to deliver oleic acid did not affect cell viability, in contrast NGFDPC12 cultures in which 0.25% MβCD concentration is used exhibited similar loss of cell viability as observed with 0.25% MβCD alone. Treating these cultures with caspase-3 inhibitor z-VAD-fmk did not protect the cells from MβCD toxic effects. (4) Immortalized Schwann cells (iSC) exposed to MβCD 0.12% did not show loss of cell viability while 0.25% MβCD triggered a significant toxicity but with a different dose and time course dynamic than NGFDPC12 cells. Thus, NGDPC12 or iSC cell cultures exposed to 0.12% MβCD exhibits normal viability while higher concentrations increase in cell death and apoptosis.

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Cholesterol deficiency increases the vulnerability of hippocampal glia in primary culture to glutamate-induced excitotoxicity

Cited by 29 publications

References 76 publications

Associative and predictive biomarkers of dementia in HIV-1–infected patients

Associative and predictive biomarkers of dementia in HIV-1–infected patients

Reyess Syndrome, Encephalopathy, Hyperammonemia and Acetyl Salicylic Acid Ingestion in a City Hospital of Buenos Aires, Argentina

Characterization of methyl-β-cyclodextrin toxicity in NGF-differentiated PC12 cell death

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