A possible neuroprotective property of ethanol and/or NeuroAiD on the modulation of cognitive function
Introduction
Alcohol (ethanol) is a brain-depressing drug possessing well known acute physiological effects (San Martin et al., 2016), including intoxication, tolerance, and dependence effects (Walls et al., 2012) which the expression of these effects depends on the dosage, time course of intoxication and type of test (Acevedo et al., 2014). In contrast to many research studies on the pathological effects of ethanol abuse, some researches have demonstrated that moderate alcohol exposure can initiate typically cytoprotective mechanisms (Collins et al., 2009). It is revealed that ethanol effects on motor control and cognitive processing are induced by changes in the activity of some ligand-gated ion channels (San Martin et al., 2016) and enzymes e. g. protein kinase A (Kumar et al., 2012), and tyrosine hydroxylase (Baizer et al., 1981). Acute behavioral effects of intraperitoneal (i.p.) administration of ethanol are observed within short periods of time in mice, proposing an immediate interaction of ethanol with some receptors and/or excitable membrane proteins in the CNS of mice (Tarragon et al., 2012). Furthermore, chronic exposure to ethanol vapors impairs cognitive function in ethanol dependent rats and can be observed during abstinence (Ewin et al., 2019).
NeuroAid, Traditional Chinese Medicine which combines extracts of 9 herbal (radix astragali, radix salviae miltiorrhizae, radix paeoniae rubrae, rhizoma chuanxiong, radix angelicae sinensis, Carthamus tinctorius, Prunus persica, radix polygalae, and rhizoma acori tatarinowii) and 5 animal components (Hirudo, Eupolyphaga seu Steleophaga, calculus bovis artifactus, Buthus martensii and cornu saigae tataricae) in capsule form, have been revealed to restore neurological and cellular function in animal models of ischemic stroke (Chen et al., 2013a). It was registered with the Sino Food and Drug Administration in 2001. There have been clinical assays, with large-scale clinical assays, of the use of NeuroAid for stroke patients (Lorivel et al., 2015). Several molecular and cellular studies demonstrated that this combination targets important pathways of neurogenesis, synaptogenesis, neuroprotection, and neurorepair as well as prevention of necrosis and apoptosis (Siddiqui et al., 2013). It has been also reported that neuroprotection and neuroplasticity effects lead to an improvement in the recovery of cognitive functions in a model of traumatic brain injury and ischemic stroke (Tsai et al., 2015). Investigation indicated that NeuroAid enhanced cognitive recovery by decreasing the hippocampal CA1 cell degeneration, DNA fragmentation, Bax expression, and increasing BDNF expression (Chen et al., 2013b). Moreover, it activates KATP channels (Moha Ou Maati et al., 2012) and induces the protein kinase B survival pathway (Quintard et al., 2011), two important mechanisms involved in neuroprotection (Liss and Roeper, 2001).
Ethanol acts on the central nervous system (CNS) to induce many behavioral effects in rodents (Correa et al., 2001). It is established that alcohol consumption caused signs of regional brain damage and cognitive dysfunction (Harper and Matsumoto, 2005), for example in exposed animals to ethanol impaired memory and learning (File and Mabbutt, 1990). On the other hand, NeuroAid has neuroprotective and anti-apoptotic effects (Quintard et al., 2011; Chan and Stanton, 2016). It showed safety and efficacy in neurological recovery after brain injuries (Chen et al., 2019; Malboosi et al., 2020; Venketasubramanian et al., 2015) as well as improvement of spatial and temporal memory impairments (Chen et al., 2013b; Quintard et al., 2011; Quintard et al., 2014). Thus, the aim of this research was to evaluate the hypothesis that ethanol exposure would cause neurobehavioral defects which may be reversed by the neuroprotective property of NeuroAid. For this, we selected some of the cognitive tasks (spatial memory, pain behavior, locomotor activity, hypnotic sensitivity, and muscle coordination) for evaluating cognitive functions in male rats. In order to assess the duration of ethanol exposure and length of abstinence, the drugs injected during 1 or 4 weeks and 1 week set as length of abstinence in male rats.
Section snippets
Animals
Adult male Wistar rats (160 rats, weighing 220–250 g and approximately 8 weeks of age) obtained from the Institute of Cognitive Science Studies (Tehran, Iran) were used in the present series of tests. Rats were born in a breeding room at the Institute of Cognitive Science Studies (Tehran, Iran) and moved to a different after weaning at postnatal day 30. They were kept in groups (4 per cage) in standard cages at 22 ± 2 °C with 40–60% humidity, a 12-h light/12-h dark cycle. Animal food prepared
Effects of i.p. injection of ethanol and/or NeuroAid on spatial memory
The aim of Experiment 1 was to measure the effect of ethanol i.p. exposures and to subsequently test rats' performance on spatial and novel recognition memories during abstinence (Fig. 1). One-way ANOVA showed that one week i.p. administration of ethanol and ethanol + NeuroAid decreased the %CAT [F(3, 22) = 85.714, P < 0.001] and %CAE [F(3, 22) = 81.133, P < 0.001], but increased latency for entering to the novel arm [F(3, 22) = 18.310, P < 0.001] compared with the control group, indicating
Discussion
Ethanol is the most generally abused drug in the world. Due to its anxiolytic and euphoric actions, it is used at moderate doses but its higher doses produce serious intoxication which leads to loss of motor coordination, sedation, and deep respiratory depression as well as death (San Martin et al., 2016). The results of the current study showed that one week abstinent of ethanol restored ethanol-induced spatial memory deficits in male rats. We note that we only these effects in male subjects;
Declaration of competing interest
No financial or other conflicts of interest are declared.
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