Spatial memory decline after masticatory deprivation and aging is associated with altered laminar distribution of CA1 astrocytes

Abstract

Background: Chewing imbalances are associated with neurodegeneration and are risk factors for senile dementia in humans and memory deficits in experimental animals. We investigated the impact of long-term reduced mastication on spatial memory in young, mature and aged female albino Swiss mice by stereological analysis of the laminar distribution of CA1 astrocytes. A soft diet (SD) was used to reduce mastication in the experimental group, whereas the control group was fed a hard diet (HD). Assays were performed in 3-, 6- and 18-month-old SD and HD mice.

Results: Eating a SD variably affected the number of astrocytes in the CA1 hippocampal field, and SD mice performed worse on water maze memory tests than HD mice. Three-month-old mice in both groups could remember/find a hidden platform in the water maze. However, 6-month-old SD mice, but not HD mice, exhibited significant spatial memory dysfunction. Both SD and HD 18-month-old mice showed spatial memory decline. Older SD mice had astrocyte hyperplasia in the strata pyramidale and oriens compared to 6-month-old mice. Aging induced astrocyte hypoplasia at 18 months in the lacunosum-moleculare layer of HD mice.

Conclusions: Taken together, these results suggest that the impaired spatial learning and memory induced by masticatory deprivation and aging may be associated with altered astrocyte laminar distribution and number in the CA1 hippocampal field. The underlying molecular mechanisms are unknown and merit further investigation.

Figure 1

Performances on the water maze tests applied to 3-, 6- and 18-month old mice were compared by determining the escape latencies on five test days. Three-month-old SD and HD mice showed similar latencies, while the escape latencies of 6-month-old HD mice were significantly shorter than those of SD age-matched mice. SD and HD 18-month-old mice did not show any significant change in escape latencies. Swimming tracking analysis revealed that SD had longer trajectories as compared to age-matched HD mice, particularly at 6 months of age (inset). HD = hard diet; SD = soft diet (* = p < 0.05 for the HD group. # = p < 0.05 for the SD group)

Figure 2

Laminar distribution and graphic representations of quantitative data of astrocytes in the CA1 hippocampal field. (A): Photomicrographs of CA1 layers in hippocampal sections from 3-, 6- and 18-month-old SD and HD mice. These sections were representative of mice that had astrocyte levels that were close to the mean values for each group. (B): The mean number and standard errors (s.e.m.) of stereological estimates of the total number of astrocytes for each CA1 layer in mice of the indicated age. (*) = Statistically significant differences (two tailed t-test; p < 0.05) between HD and SD age-matched mice. (#) = Statistically significant differences between SD and HD mice of different ages. LacMol. = stratum lacunosum-moleculare; Rad = stratum radiatum; Py = stratum pyramidale; Or = stratum oriens; HD = hard diet; SD = soft diet; 3 M, 6 M and 18 M indicate 3-month-old, 6-month-old and 18-month-old mice, respectively. Scale bar = 25 μm