Acute Administration of Methyleugenol Impairs Hippocampus-Dependent Contextual Fear Memory and Increases Anxiety-like Behavior in Mice

Abstract

Methyleugenol (ME) as a natural essential oil in many plant species is widely used in human food and beverage for its fragrance and possible beneficial health effects. Previous chronic or subacute studies in rodents show that ME mainly causes liver toxicity. However, whether and how acute ME affects the central nervous system still remain elusive. Here, we found that ME administrated into the hippocampus impaired the acquisition of hippocampus-dependent contextual fear memory in mice (ME vs control: repeated-measures two-way ANOVA, F (5,70) = 2.937, p < 0.05; Fisher test, p < 0.05, respectively, 53 ± 5.2% vs 73 ± 7.6% during trial 4 and 46.8 ± 6% vs 74.5 ± 9.3% during trial 5). Meanwhile, acute ME impaired hippocampal CA1 long-term potentiation (LTP; ME vs control: independent t-test, p < 0.01, 110.6 ± 1.8% vs 133.3 ± 5.6%) while facilitated long-term depression (LTD; p < 0.01, 75.7 ± 3.4% vs 88.6 ± 1.7%) in mice brain slices and inducing a decrease in learning-dependent phosphorylation of Ser831 (ME vs control: independent t-test, p < 0.001, 0.87 ± 0.03 vs 1.23 ± 0.03) and Ser845 (p < 0.01, 0.42 ± 0.07 vs 0.97 ± 0.14) sites of excitatory glutamate AMPA receptor subunit 1 (GluA1) in the hippocampus, which may be the underlying mechanisms of impairment of hippocampus-dependent learning. In addition, intrahippocampal infusion of ME also increased anxiety-like behaviors in mice. These results suggested that acute ME impaired the hippocampus function at behavioral, cellular, and molecular levels, indicating the potential risks of ME on the central nervous system.

Crateva unilocularis Buch. shoots attenuate d-galactose-induced brain injury and cognitive disorders of mice through the PI3K/Akt/Nrf2 pathway

“…Open field (1 day) and elevated plus (1 day) tests were used to assess the anxiety level, and Y-maze (1 day) and fear conditioning (4 days) tests were applied to evaluate the learning and memory abilities of mice. These four experiments were strictly in accordance with the previous reports, [23][24][25] and each experiment was conducted with a one day gap.…”

“…The proportion of time spent in the central area of the open field test and the open arm of the elevated plus maze are used to evalu- ate the anxiety level, and the total travel distance during locomotion is applied as an index of spontaneous activity. 23 In the open field test, the D-gal-induced mice (group M) spent significantly less time in the central area ( p < 0.05, Fig. 6A), but without statistical difference in the total movement distance in comparison with the mice in group C (Fig.…”

Assessment of attractancy and safeness of (E)‐coniferyl alcohol for management of female adults of Oriental fruit fly, Bactrocera dorsalis (Hendel)

“…The hepatotoxicity, cytotoxicity, and carcinogenesis of ME in rodents have been well documented. [50][51][52] Prior studies have revealed three possible metabolic pathways of ME in mammals: 1 0 -hydroxylation of ME to 1 0 -OH ME, epoxidation of the side chain alkene to 2 0 ,3 0 -epoxide, and O-demethylation of ME to phenols. 53,54 To date, there has been no mention of E-CF as a by-product.…”

“…Recent research also indicated that acute ME impaired hippocampus function at behavioral, cellular and molecular levels, indicating the potential risks of ME on the central nervous system in mice. In addition, acute ME also enhances mice anxiety 52 . Conversely, males of B. dorsalis detoxify ME using a simple oxidative process and convert ME into less harmful by‐products (DMP and E‐CF) to be sequestered into the rectal gland for emission at dusk 39,56 .…”

Effects of Tarragon Hydroalcoholic Extract and Coumarin On Memory, Tissue Index and GABAA Receptor Gene Expression in The Hippocampus of Male Rats

“…The ndings of the research showed that the intraventricular injection of methyl eugenol to rats ended in the increase of tension in rats. Meanwhile, methyl eugenol extremely caused hippocampus functional disorder at behavioural, cellular and molecular levels and this indicated potential dangers of methyl eugenol to the central nervous system (32).…”