Moderate to high ethanol and acetaldehyde administration decreases c-fos protein expression in the hippocampus of Aldh2-knockout and C57BL/6N mice

Ayako Ito,Hiroshi Kinoshita,Kiyoshi Ameno,Mostofa Jamal,Naoko Tanaka,Takanori Miki

doi:10.3329/bjms.v19i1.43876

Abstract

Background: Ethanol (EtOH) and acetaldehyde (AcH) have long been associated with many adverse effects in the central nervous system. c-fos has been used as an indirect index of neural activity. Method: Here, we investigated the effects of systemic administration of EtOH and AcH on the expression of c-fos protein in the hippocampus of Aldh2-knockout (Aldh2-KO) mice. The animals received an intraperitoneal injection of saline (control), EtOH (1.0, 2.0 and 4.0 g/kg) or AcH (50, 100 and 200 mg/kg), and the expression of c-fos protein was measured by Western blotting. Result: We found that EtOH at doses of 2.0 and 4.0 g/kg decreased c-fos in wild-type (WT) mice, whereas EtOH at all three doses tested (1.0-4.0 g/kg) decreased c-fos in Aldh 2-KO mice. Likewise, AcH at doses of 100 and 200 mg/kg had a significant effect in lowering c-fos protein in both WT and Aldh2-KO mice. Conclusion: Our observations suggest that moderate to high EtOH and AcH can decrease the expression of c-fos protein in the mouse hippocampus. This effect may support, at least in part, the link between c-fos and spatial memory deficits following EtOH and AcH exposure as we have observed in our previous study. Bangladesh Journal of Medical Science Vol.19(1) 2020 p.83-89

Highlights

Ethanol (EtOH) and acetaldehyde (AcH) have numerous pharmacological and neurobehavioral effects; some of the effects of EtOH are mediated by its first metabolite AcH
Neurons can respond to extracellular stimulation by modulating the expression of certain immediate early genes, most importantly c-fos, which is known to play an important role in neuronal adaptations and brain plasticity5,6. c-fos is widely distributed in the rat brain, in the cortex, hippocampus and cerebellum[7,8], and has been associated with memory[9,10]
For Aldh2-KO mice, the post hoc analysis with the Tukey–Kramer test showed that treatment with 100 (P=0.04) and 200 mg/kg (P=0.002) of AcH resulted in a significant decrease in the level of c-fos when compared with the administration of saline

Summary

Introduction

Ethanol (EtOH) and acetaldehyde (AcH) have numerous pharmacological and neurobehavioral effects; some of the effects of EtOH are mediated by its first metabolite AcH. Western blotting (WB) was used to measure c-fos protein expression in the hippocampus of Aldh2-KO and wild-type (WT) mice 60 min after the i.p. administration of saline, EtOH (1.0, 2.0 and 4.0 g/kg) or AcH (50, 100 and 200 mg/ kg).

Results

Conclusion