Anat Cell Biol.  2017 Jun;50(2):143-151. 10.5115/acb.2017.50.2.143.

Vanillin and 4-hydroxybenzyl alcohol attenuate cognitive impairment and the reduction of cell proliferation and neuroblast differentiation in the dentate gyrus in a mouse model of scopolamine-induced amnesia

• Kim YH
• Park JH

• KMID: 2451240
• DOI: http://doi.org/10.5115/acb.2017.50.2.143

Abstract

4-Hydroxy-3-methoxybenzaldehyde (vanillin) and 4-hydroxybenzyl alcohol (4-HBA) are natural phenolic compounds, which present in many plants and have diverse biological properties. In this study, we examined effects of vanillin and 4-HBA on learning and memory function, cell proliferation, and neuroblast differentiation in the hippocampal dentate gyrus in a mouse model of scopolamine-induced amnesia. Scopolamine (SCO; 1 mg/kg/day, intraperitoneally), vanillin, and 4-HBA (40 mg/kg/day, orally) were administered for 28 days. Treatment with scopolamine alone impaired learning and memory function in the Morris water maze and passive avoidance tests, in addition, the treatment significantly reduced cell proliferation and neuroblast differentiation in the dentate gyrus, which were examined by immunohistochemistry for Ki-67 (a classic marker for cell proliferation) and doublecortin (a marker for neuroblasts). However, treatment with vanillin or 4-HBA significantly attenuated SCO-induced learning and memory impairment as well as the reduction of cell proliferation and neuroblast differentiation in the dentate gyrus. These results indicate that vanillin and 4-HBA may be helpful in improving cognitive function and in increasing endogenous neuronal proliferation in the brain.

Keyword

Learning and memory; Hippocampus; Scopolamine; Phenolic compounds; Neurogenesis

MeSH Terms

Amnesia*
Animals
Brain
Cell Proliferation*
Cognition
Cognition Disorders*
Dentate Gyrus*
Hippocampus
Immunohistochemistry
Learning
Memory
Mice*
Neurogenesis
Neurons
Phenol
Scopolamine Hydrobromide
Water
Phenol
Scopolamine Hydrobromide
Water

Figure

• 

  Fig. 1 The latency of Morris water maze (A) and passive avoidance tests (B) in the vehicle, scopolamine (SCO), SCO+vanillin, and SCO+4-hydroxybenzyl alcohol (4-HBA) groups (n=7 per group in each test; *P<0.05, significantly different from the vehicle group, #P<0.05, significantly different from the SCO group). The bars indicate the means±SEM.

• 

  Fig. 2 Immunohistochemistry for Ki-67 in the dentate gyrus of the vehicle (A), scopolamine (SCO) (B), SCO+ vanillin (C), and SCO+4-hydroxybenzyl alcohol (4-HBA) (D) groups. In the vehicle group, Ki-67–immunoreactive cells (arrows) are shown in the subgranular zone. Ki-67-immunoreactive cells are significantly decreased in the SCO group; however, they are increased in the SCO+vanillin and SCO+4-HBA groups. GCL, granule cell layer; ML, molecular layer; PL, polymorphic layer. Scale bar=100 µm. (E) The mean number of Ki-67–immunoreactive cells per group (n=14 per group; *P<0.05, significantly different from the vehicle group, #P<0.05, significantly different from the SCO group). The bars indicate the means±SEM.

• 

  Fig. 3 Immunohistochemistry for doublecortin (DCX) in the dentate gyrus of the vehicle (A, B), scopolamine (SCO) (C, D), SCO+vanillin (E, F), and SCO+4-hydroxybenzyl alcohol (4-HBA) (G, H) groups. In the vehicle group, DCX-immunoreactive cells (arrowheads) have well-developed dendrites that extend into the molecular layer (ML, arrows). A few DCX-immunoreactive cells with short dendrites are found in the SCO group; however, numbers of DCX-immunoreactive cells and their dendrites are reversed in both SCO+vanillin and SCO+4-HBA group. GCL, granule cell layer; PL, polymorphic layer. Scale bars=100 (A, C, E, G) µm, 50 (B, D, F, H) µm. (I) The mean number of DCX-immunoreactive cells per group (n=14 per group; *P<0.05, significantly different from the vehicle group, #P<0.05, significantly different from the SCO group). The bars indicate the means± SEM.

• 

  Fig. 4 NeuN immunohistochemistry (A, C, E, G) and Fluoro-Jade B (F-J B) histofluorescence staining (B, D, F, H) in the dentate gyrus of the vehicle (A, B), scopolamine (SCO) (C, D), SCO+vanillin (E, F), and SCO+4-hydroxybenzyl alcohol (4-HBA) (G, H) groups. There is no difference in the distribution pattern of NeuN-immunoreactive neurons between all groups, and no F-J B–positive cells are detected in all groups. GCL, granule cell layer; ML, molecular layer; PL, polymorphic layer. Scale bar=100 µm. The bars indicate the means±SEM.

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