Are oxidative mechanisms primary in ethanol induced Purkinje neuron death of the neonatal rat?

Pierce, Dwight R.; Cook, Cody C.; Hinson, Jack; Light, Kim E.

doi:10.1016/j.neulet.2006.02.025

Cited by 13 publications

(12 citation statements)

References 27 publications

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“…This was notable based on previous work of other investigators and current hypotheses (Heaton et al, 2000a;Heaton et al, 2003;Heaton et al, 2002;Henderson et al, 1995;Ramachandran et al, 2003;Siler-Marsiglio et al, 2004;Siler-Marsiglio et al, 2005b). However, it is consistent with reports from several investigators suggesting that oxidative stress is not involved in ethanol neurotoxicity (Edwards et al, 2002;Grisel and Chen, 2005;Pierce et al, 2006;Smith et al, 2005;Tran et al, 2005). That being said, the present findings do not exclude the possibility that ethanol produces oxidative stress that contributes to neuronal death.…”

Section: Discussionsupporting

confidence: 91%

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Ethanol exposure of neonatal rats does not increase biomarkers of oxidative stress in isolated cerebellar granule neurons

Kane

Chang

Roberson

et al. 2008

Alcohol

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Oxidative stress is a candidate mechanism for ethanol neuropathology in Fetal Alcohol Spectrum Disorders. Oxidative stress often involves production of reactive oxygen species (ROS), deterioration of the mitochondrial membrane potential (MMP), and cell death. Previous studies have produced conflicting results regarding the role of oxidative stress and the benefit of antioxidants in ethanol neuropathology in the developing brain. This study investigated the hypothesis that ethanol neurotoxicity involves production of ROS with negative downstream consequences for MMP and neuron survival. This was modeled in neonatal rats at postnatal day 4 (P4) and P14. It is well established that granule neurons in the rat cerebellar cortex are more vulnerable to ethanol neurotoxicity on P4 than at later ages. Thus, it was hypothesized that ethanol produces more oxidative stress and its negative consequences on P4 than on P14. A novel experimental approach was employed in which ethanol was administered to animals in vivo (gavage 6g/kg), granule neurons were isolated 2-24 hr post-treatment, and ROS production and relative MMP were immediately assessed in the viable cells. Cells were also placed in culture and survival was measured 24 hr later. The results revealed that ethanol did not induce granule cells to produce ROS, cause deterioration of neuronal MMP, or cause neuron death when compared to vehicle controls. Further, granule neurons from neither P4 nor P14 animals mounted an oxidative response to ethanol. These findings do not support the hypothesis that oxidative stress is obligate to granule neuron death following ethanol exposure in the neonatal rat brain. Other investigators have reached a similar conclusion using either brain homogenates or cell cultures. In this context, it is likely that oxidative stress is not the sole and perhaps not the principal mechanism of ethanol neurotoxicity for cerebellar granule neurons during this stage of brain development.

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Section: Discussionsupporting

confidence: 91%

“…However, other studies have failed to support the hypothesis (Edwards et al, 2002;Grisel and Chen, 2005;Pierce et al, 2006;Smith et al, 2005;Tran et al, 2005). The present study employed a unique combination of features to address the hypothesis.…”

Section: Discussionmentioning

confidence: 83%

Ethanol exposure of neonatal rats does not increase biomarkers of oxidative stress in isolated cerebellar granule neurons

Kane

Chang

Roberson

et al. 2008

Alcohol

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“…One mechanism by which ethanol can damage CNS tissue and augment apoptosis is by increasing oxidative stress (Montoliu et al, 1995; Heaton et al, 2003b; Ramachandran et al, 2003; Marino et al, 2004; Pierce et al, 2006). The brain is particularly susceptible to oxidative stress because of its high oxygen consumption, high polyunsaturated fatty acid content, and low antioxidant defenses (Gruener et al, 1991; Lau et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant neuroprotection against ethanol-induced apoptosis in HN2-5 cells

2009

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Earlier studies from this and other laboratories show that ethanol induces apoptotic death of fetal and neonatal neurons. One mechanism that underlies these effects is the ethanol-associated reduction in the phosphatidylinositol 3′ kinase pro-survival pathway. Another mechanism involves the oxidative stress caused by the ethanol-associated increase in reactive oxygen species (ROS).In the present study, we used the murine HN2-5 hippocampal-derived cell line to investigate the effects of ethanol on ROS levels and apoptosis. We also investigated the potential neuroprotective effects of two structurally unrelated antioxidants: N-acetylcysteine (NAC) and melatonin. The results demonstrate that NAC blocked an ethanol-associated increase in ROS. In addition, NAC and melatonin prevented the augmentation of apoptosis in ethanol-treated neurons. Both antioxidants significantly elevated the expression of the anti-apoptotic gene XIAP in ethanol-treated and/or control neurons and melatonin increased Bcl-2 expression in ethanol-treated neurons. Thus, it is possible that the neuroprotective effects of NAC and melatonin involve their ability to augment the expression of one or more anti-apoptotic gene as well as their classical antioxidant actions. Additional studies are needed to establish the effectiveness of these antioxidants to prevent the loss of neurons which accompanies in utero exposure to ethanol.

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“…For example, Kane et al (2008) showed that ethanol does not induce rat cerebellar granule neurons to produce ROS and cause deterioration of the mitochondrial membrane potential. Antioxidants ( N -acetylcysteine, U83836E, and melatonin) fail to protect ethanol-induced Purkinje cell loss in the developing rat cerebellum due to alcohol administration (Edwards et al 2002; Grisel and Chen 2005; Pierce et al 2006). Tran et al (2005) showed that vitamin E does not protect against ethanol-induced cerebellar damage or deficits in eyeblink classical conditioning in rats.…”

Section: Approaches Using Antioxidants To Alleviate Ethanol Neurotoximentioning

confidence: 99%

Anthocyanins: Are They Beneficial in Treating Ethanol Neurotoxicity?

Chen

Luo

2009

Neurotox Res

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Heavy alcohol exposure produces profound damage to the developing central nervous system (CNS) as well as the adult brain. Children with fetal alcohol spectrum disorders (FASD) have a variety of cognitive, behavioral, and neurological impairments. FASD currently represents the leading cause of mental retardation. Excessive alcohol consumption is associated with Wernicke–Korsakoff syndrome (WKS) and neurodegeneration in the adult brain. Although the cellular/molecular mechanism underlying ethanol’s neurotoxicity has not been fully understood, it is generally believed that oxidative stress plays an important role. Identification of neuroprotective agents that can ameliorate ethanol neurotoxicity is an important step for developing preventive/therapeutic strategies. Targeting ethanol-induced oxidative stress using natural antioxidants is an attractive approach. Anthocyanins, a large subgroup of flavonoids present in many vegetables and fruits, are safe and potent antioxidants. They exhibit diverse potential health benefits including cardioprotection, anti-atherosclerotic activity, anti-cancer, anti-diabetic, and anti-inflammation properties. Anthocyanins can cross the blood–brain barrier and distribute in the CNS. Recent studies indicate that anthocyanins represent novel neuroprotective agents and may be beneficial in ameliorating ethanol neurotoxicity. In this review, we discuss the evidence and potential of anthocyanins in alleviating ethanol-induced damage to the CNS. Furthermore, we discuss possible underlying mechanisms as well as future research approaches necessary to establish the therapeutic role of anthocyanins.

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Are oxidative mechanisms primary in ethanol induced Purkinje neuron death of the neonatal rat?

Cited by 13 publications

References 27 publications

Ethanol exposure of neonatal rats does not increase biomarkers of oxidative stress in isolated cerebellar granule neurons

Ethanol exposure of neonatal rats does not increase biomarkers of oxidative stress in isolated cerebellar granule neurons

Antioxidant neuroprotection against ethanol-induced apoptosis in HN2-5 cells

Anthocyanins: Are They Beneficial in Treating Ethanol Neurotoxicity?

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