Vanillin improves scopolamine‑induced memory impairment through restoration of ID1 expression in the mouse hippocampus

Abstract

4-Hydroxy-3-methoxybenzaldehyde (vanillin), contained in a number of species of plant, has been reported to display beneficial effects against brain injuries. In the present study, the impact of vanillin on scopolamine‑induced alterations in cognition and the expression of DNA binding protein inhibitor ID‑1 (ID1), one of the inhibitors of DNA binding/differentiation proteins that regulate gene transcription, in the mouse hippocampus. Mice were treated with 1 mg/kg scopolamine with or without 40 mg/kg vanillin once daily for 4 weeks. Scopolamine‑induced cognitive impairment was observed from 1 week and was deemed to be severe 4 weeks following the administration of scopolamine. However, treatment with vanillin in scopolamine‑treated mice markedly attenuated cognitive impairment 4 weeks following treatment with scopolamine. ID1‑immunoreactive cells were revealed in the hippocampus of vehicle‑treated mice, and were hardly detected 4 weeks following treatment with scopolamine. However, treatment with vanillin in scopolamine‑treated mice markedly restored ID1‑immunoreactive cells and expression 4 weeks subsequent to treatment. The results of the present study suggested that vanillin may be beneficial for cognitive impairment, by preventing the reduction of ID1 expression which may be associated with cognitive impairment.

Keywords: muscarinic acetylcholine receptor; cholinergic transmission; cognitive deficits; DNA binding protein inhibitor; 4-hydroxy-3-methoxybenzaldehyde.

Figure 1.

Effects of vanillin against the scopolamine-induced alteration of cognitive defects. (A) Passive avoidance test. (B) Morris water maze test. n=14 mice/group. *P<0.05 vs. vehicle; ^#P<0.05 vs. Sco. Error bars indicate the mean ± standard error of the mean. Sco, scopolamine-treated; Sco/Van, scopolamine/vanillin-cotreated.

Figure 2.

Western blot analysis of ID1 in the hippocampus. Cotreatment with scopolamine and vanillin restored the ID1 level at 4 weeks following cotreatment. ROD as percentage values of the immunoblot band is presented. n=7 mice/group. *P<0.05 vs. vehicle; ^#P<0.05 vs. Sco at 4 weeks. Error bars indicate the mean ± standard error of the mean. Sco, scopolamine-treated; Sco/Van, scopolamine/vanillin-cotreated; ID1, DNA binding protein inhibitor ID-1; ROD, relative optical density.

Figure 3.

ID1 immunohistochemistry in the CA1, CA2/3 and dentate gyrus (DG) regions of the vehicle-treated (A, F, K), scopolamine-treated (B-D, G-I, L-N), and scopolamine/vanillin-treated mice (E, J, O). ID1-immunoreactive cells (arrows) in the vehicle-treated mice were observed in CA1-3 and the dentate gyrus. In the scopolamine-treated mice, ID1-immunoreactive cells were markedly decreased from 1 week post-treatment with scopolamine. In the cotreated mice, ID1-immunoreactive cells were markedly increased compared with the vehicle-treated mice. Scale bar, 100 µm. (P, Q and R) ROD as percentage values of ID1 immunoreactivity in the mouse hippocampus. n=7 mice/group. *P<0.05 vs. vehicle; ^#P<0.05 vs. Sco at 4 weeks. Error bars indicate the mean ± standard error of the mean. GCL, granule cell layer; ML, molecular layer; PL, polymorphic layer; SO, stratum oriens; SP, stratum pyramidale; SR, stratum radiatum; Sco, scopolamine-treated; Sco/Van, scopolamine/vanillin-cotreated; ID1, DNA binding protein inhibitor ID-1; ROD, relative optical density.