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

Abstract

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.

Fetal alcohol-induced hyperactivity is reversed by treatment with the PPARα agonist fenofibrate in a rat model

“…Firstly, some neurotransmission systems have demonstrated therapeutic potential in FASD (Choong and Shen 2003;Ryan et al 2008;Shen and Choong 2006;Thomas et al 2004Thomas et al , 2007Xu and Shen 2001), and PPAR-alpha was able to modulate those systems (De La Monte et al 2006;Farioli-Vecchioli et al 2001;Galan-Rodriguez et al 2009;Melis et al 2008). Secondly, there are reports of the value of anti-oxidant treatments in countering the harmful effects of in utero exposure to alcohol (Ramachandran et al 2003;Rathinam et al 2006;Sheth et al 2009), and PPAR-alpha constitutes a pharmacological target that is likely to modulate several downstream physiopathological pathways involved in neuronal survival, including those that protect the cell from oxidative stress (Bordet et al 2006;Girnun et al 2002).…”

Melatonin and oestrogen treatments were able to improve neuroinflammation and apoptotic processes in dentate gyrus of old ovariectomized female rats

“…Nopparat et al (2010) have demonstrated, in the SK-N-SH dopaminergic cell line, a novel role of melatonin in protecting cells from autophagic cell death triggered by the Bcl-2/Beclin 1 pathway, by inhibiting the activation of the JNK1 (cJun amino-terminal kinase), Bcl-2 upstream pathway. Melatonin increased Bcl-2 and augmented expression of XIAP in ethanol-treated HN2-5 (mouse hippocampal neuron-derived) cells (Shetha et al 2009). Our results also demonstrated an increase in the mRNA expression of AIF in the dentate gyrus of old and ovariectomized rats, and this could suggest that this brain area was following a different apoptotic pathway.…”

Promising Role of Melatonin as Neuroprotectant in Neurodegenerative Pathology

“…It attenuates apoptosis and oxidative stress in neurons and mesenchymal stem cells by upregulating the antiapoptotic protein bcl-2 [83,84]. It also alters the cell death processes in response to age-related oxidative stress and apoptosis in the brain of senescenceaccelerated mice [85]. It inhibits the ethanol-induced increased ROS level and increases the bcl-2 expression in murine HN2-5 hippocampus-derived cell line [86].…”