Effects of ethanol on calcium homeostasis in the nervous system

Catlin, Michelle C.; Guizzetti, Marina; Costa, Lucio G.

doi:10.1007/bf02741375

Cited by 33 publications

(16 citation statements)

References 156 publications

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“…This may indicate a loss of vessel integrity and enhanced vascular shaping. Some of the effects of EtOH may also be modulated by its antiproliferative effect on astrocytes (Costa et al, 2004) or maintenance of calcium homeostasis (Catlin et al, 1999). Our data also show that cholesterol did not markedly affect the EtOH-induced changes.…”

Section: Discussionmentioning

confidence: 99%

Effects of long-term moderate ethanol and cholesterol on cognition, cholinergic neurons, inflammation, and vascular impairment in rats

Ehrlich¹,

Pirchl²,

Humpel³

2012

Neuroscience

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There is strong evidence that vascular risk factors play a role in the development of Alzheimer's disease (AD) or vascular dementia (vaD). Ethanol (EtOH) and cholesterol are such vascular risk factors, and we recently showed that hypercholesterolemia causes pathologies similar to AD [Ullrich et al. (2010) Mol Cell Neurosci 45, 408–417]. The aim of this study was to investigate the effects of long-term (12 months) EtOH treatment (20% v/v in drinking water) alone or long-term 5% cholesterol diet alone or a combination (mix) in adult Sprague–Dawley rats. Long-term EtOH treatment (plasma EtOH levels 58±23 mg/dl) caused significant impairment of spatial memory, reduced the number of choline acetyltransferase- and p75 neurotrophin receptor-positive nucleus basalis of Meynert neurons, decreased cortical acetylcholine, elevated cortical monocyte chemoattractant protein-1 and tissue-type plasminogen activator, enhanced microglia, and markedly induced anti-rat immunoglobulin G-positive blood–brain barrier leakage. The effect of long-term hypercholesterolemia was similar. Combined long-term treatment of rats with 20% EtOH and 5% cholesterol (mix) did not potentiate treatment with EtOH alone, but instead counteracted some of the EtOH-associated effects. In conclusion, our data show that vascular risk factors EtOH and cholesterol play a role in cognitive impairment and possibly vaD.

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Section: Discussionmentioning

confidence: 99%

Effects of long-term moderate ethanol and cholesterol on cognition, cholinergic neurons, inflammation, and vascular impairment in rats

Ehrlich¹,

Pirchl²,

Humpel³

2012

Neuroscience

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“…Several mechanisms have been proposed for ethanol‐induced neuronal loss; these include: 1) inducing oxidative stress; 2) disrupting neurotrophic signaling and intracellular calcium homeostasis; 3) inhibiting the proliferation of neuronal precursors; and 4) altering neurotransmitter systems (Luo et al,1997; Webb et al,1997; Luo and Miller,1998; Catlin et al,1999; Ikonomidou et al,2000; Goodlett and Horn,2001; de la Monte and Wands,2002; Davies,2003; Kumral et al,2005). The action of alcohol is complex.…”

Section: Discussionmentioning

confidence: 99%

Ethanol promotes endoplasmic reticulum stress‐induced neuronal death: Involvement of oxidative stress

Chen

Bower

et al. 2007

J of Neuroscience Research

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One of the most devastating effects of ethanol exposure during development is the loss of neurons in selected brain areas. The underlying cellular/molecular mechanisms remain unclear. The endoplasmic reticulum (ER) is involved in posttranslational protein processing and transport. The accumulation of unfolded or misfolded proteins in the ER lumen triggers ER stress, which is characterized by translational attenuation, synthesis of ER chaperone proteins such as GRP78, and activation of transcription factors such as ATF4, ATF6, and CHOP. Sustained ER stress ultimately leads to cell death. ER stress response can be induced experimentally by treatment with tunicamycin and thapsigargin. Using SH-SY5Y neuroblastoma cells and primary cerebellar granule neurons as in vitro models, we demonstrated that exposure to ethanol alone had little effect on the expression of markers for ER stress; however, ethanol drastically enhanced the expression of GRP78, CHOP, ATF4, ATF6, and phosphorylated PERK and elF2α when induced by tunicamycin and thapsigargin. Consistently, ethanol promoted tunicamycin-and thapsigargininduced cell death. Ethanol rapidly caused oxidative stress in cultured neuronal cells; antioxidants blocked ethanol's potentiation of ER stress and cell death, suggesting that the ethanol-promoted ER stress response is mediated by oxidative stress. CHOP is a proapoptotic transcription factor. We further demonstrated that CHOP played an important role in ethanol-promoted cell death. Thus, the effect of ethanol may be mediated by the interaction between oxidative stress and ER stress. Keywordsalcohol; apoptosis; cerebellum; development; fetal alcohol syndrome Alcohol exposure alters the structure and physiology of the brain in many ways. During development, alcohol-induced structural and physiological alterations contribute to the brain dysfunction of children with fetal alcohol syndrome (FAS). FAS is the most common nonhereditary cause of mental retardation (May and Gossage, 2001). One of the most prominent alcohol-induced neuropathological changes in the developing brain is the loss of neurons (West et al., 1990;Luo and Miller, 1998;Ikonomidou et al., 2000; Goodlet and © 2007 Horn, 2001). In adults, heavy alcohol consumption also causes neuronal loss in selected brain regions (Kril et al., 1997;Gotz et al., 2001;Ikegami et al., 2003). The mechanisms underlying ethanol-induced neuronal loss, however, remain incompletely elucidated. Oxidative stress is caused by the disruption of intracellular redox homeostasis. The generation of reactive oxygen species (ROS) initiates this process and may cause neuronal death (Mattson et al., 2001;Watts et al., 2005;Loh et al., 2006). Alcohol exposure may induce oxidative stress in the central nervous system (Marino et al., 2004;Kumral et al., 2005;Chu et al., 2007), and the brain is particularly susceptible to ROS-induced damage (Annunziato et al., 2003). Oxidative stress has been proposed to be a potential mechanism for ethanol-induced damage (Sun et al., 2001;Chu et al., 2...

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“…In the present study, we used 50 mM ethanol for sustained exposure to examine changes of L-type HVCCs because the previous studies demonstrated that 50 -100 mM ethanol in vivo is relevant to the blood ethanol concentrations in clinical populations (31). Moreover, the blood ethanol concentration in animals with ethanol physical dependence induced by sustained ethanol vapor administration employed here was about 290 mg / dl of blood (23), and this blood concentration is considered to be similar to 50 mM ethanol concentration in vitro.…”

Section: Discussionmentioning

confidence: 99%

Increase in Expression of α1 and α2/δ1 Subunits of L-Type High Voltage-Gated Calcium Channels After Sustained Ethanol Exposure in Cerebral Cortical Neurons

et al. 2006

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Abstract. Previous reports revealed up-regulation of L-type high voltage-gated calcium channels (HVCCs) in mouse brains with ethanol physical dependence. We investigated mechanisms of enhancement of L-type HVCC function using mouse cerebrocortical neurons exposed to 50 mM ethanol for 3 days and the brains of mouse physically dependent on ethanol. Ethanol facilitated 30 mM KCl-stimulated 45 Ca 2+ influx in dose-and duration-dependent manners, which was abolished by nifedipine, an inhibitor specific to L-type HVCCs, but not by inhibitors for other types of HVCCs. Increase in [3 H]PN200-110 binding to the particulate fractions from the ethanol-treated neurons was due to increased B max value with no changes in K d value. Western blot analysis showed the increased expression of α1C, α1D, and α2/ δ1 subunits with decreased β4 subunit expression and no changes in expressions of α1A, α1B, α1F, and α2 subunits. A similar pattern of the changes in the expression of these subunits of L-type HVCCs were observed in the cerebral cortex from mouse with ethanol physical dependence. These results indicate that sustained ethanol exposure to the neurons induces up-regulation of L-type HVCCs, which is due to increased expressions of α1C, α1D, and α2 / δ1 subunits, and produces no alterations in P / Q-and N-type HVCC functions.

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Effects of ethanol on calcium homeostasis in the nervous system

Cited by 33 publications

References 156 publications

Effects of long-term moderate ethanol and cholesterol on cognition, cholinergic neurons, inflammation, and vascular impairment in rats

Effects of long-term moderate ethanol and cholesterol on cognition, cholinergic neurons, inflammation, and vascular impairment in rats

Ethanol promotes endoplasmic reticulum stress‐induced neuronal death: Involvement of oxidative stress

Increase in Expression of α1 and α2/δ1 Subunits of L-Type High Voltage-Gated Calcium Channels After Sustained Ethanol Exposure in Cerebral Cortical Neurons

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