Ethanol Consumption Affects Neuronal Function: Role of the Mitochondria

Abstract

Ethanol is a licit drug consumed by a large part of the population, from adolescence to adulthood. High ethanol consumption is a public health problem due to its addictiveness and the risk it produces of developing other diseases, including cardiovascular, hepatic, and mental pathologies. Different patterns of ethanol consumption and its toxic effects in the brain have been reported. Current studies suggest to mitochondria, one of the principal mediators for ethanol neurotoxicity. In this chapter, we will review the effects of ethanol on neurons in different scenarios of ethanol consumption and its relation with mitochondrial function. Finally, we will propose a mechanism of ethanol toxicity in which the mitochondria are the main mediator and in which the mitochondrial alterations correlate with the severity of ethanol consumption. Thus, improving mitochondrial health of brain cells could be considered as a potential therapeutic target to treat ethanol-associated disorders.Excessive ethanol use results in brain intoxication, leading to motor and behavior alterations, and eventually to death as a consequence of the depressive effects on the central nervous system (CNS) [6]. These effects result in simultaneous alterations in neuronal circuits including the prefrontal cortex, which controls behavior [7]; the cerebellum, which regulates movement and coordination [8]; the frontal lobe, which controls emotions [9]; the reticular activating system, which determines the sleep-wake cycle [10]; the hippocampus, which mediates learning and memory [8]; and the medulla, which controls vital functions [6]. Ethanol intoxication induces cellular damage and neuronal death [11]. The precise mechanism participating in ethanol toxicity in the brain is unknown. However, at the cellular level, ethanol impairs the neurotransmitters signaling [12]. Also, ethanol promotes reactive oxygen species (ROS) production [13] and activates inflammatory processes [14]. Altogether these events could be responsible for ethanol-induced damage in the brain.Mitochondria are dynamic organelles, which regulate the production of ATP, redox balance, and calcium homeostasis in the neuron [15]. Interestingly, many effectors described in ethanol toxicity are directly or indirectly related to mitochondria. Mitochondria are the main source of ROS in the brain, and they are mainly affected by the oxidative damage induced by ethanol intoxication [16]. Likewise, dysfunctional mitochondria play a role in inducing proinflammatory events [17]. Finally, during synaptic process, ATP production and calcium buffering capacity produced by mitochondria are critical [18,19]; therefore, mitochondrial injury may have severe consequences on neuronal communication.In fact, evidence suggests that ethanol produces catastrophic changes in the mitochondria of organs such as liver [20] and heart [21], and over the last decade, many studies have reported the toxicity of ethanol to the brain's mitochondria [22,23]. Briefly, ethanol increases ROS production [23], alters mitochondrial ...

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids

“…Previous findings from animal studies suggest that mitochondria appear to be a major target of ethanol toxicity in the brain. Reactive oxygen species (ROS) and reactive nitrogen species (RNS)-associated disturbances of the integrity of the mitochondrial membrane and decreased mitochondrial genes were important mediators for the ethanolinduced brain cell injuries [124][125][126] . However, mitochondrial respiration capacity was not investigated in the FASD research fields.…”

Neurochemical mechanisms underlying acute and chronic ethanol-mediated responses in zebrafish: The role of mitochondrial bioenergetics

“…Thus, we suggest that part of the O 2 is not being consumed by mitochondria, but rather by other EtOH detoxification pathways (e.g., catalase and CYP450 enzymes), which are directly involved in EtOH metabolism (Moghe et al, 2011). Oxidative damage after chronic EtOH exposure can alter the fluidity of the mitochondrial membrane (Kowaltowski et al, 2009;Tapia-Rojas, 2018), disrupt the mitochondrial membrane potential (Karadayian et al, 2015), and reduce the mitochondrial complexes I, III, and IV activities, which are necessary for ATP formation (Bustamante et al, 2012;Karadayian et al, 2015).…”

Ketamine plus Alcohol: What We Know and What We Can Expect about This

“…In an abstinence context, ketamine and ethanol also share deleterious mechanisms, involving overspread glutamatergic excitotoxicity, resulting in oxidative stress, mitochondrial dysfunction, neuroinflammation, and cell death induction [ 200 , 201 ]. These hazardous processes have been associated with genesis and poor outcomes of several CNS diseases, such as depression and anxiety [ 108 , 146 , 147 , 148 , 150 ].…”