Transplanted bone marrow mesenchymal stem cells improve memory in rat models of Alzheimer's disease

Abstract

The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs) grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months) were tested in Morris water maze (MWM) and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500 × 10(3)/μL) and PBS (phosphate buffer saline). In the second experiment, Ibotenic acid (Ibo) was injected bilaterally into the nucleus basalis magnocellularis (NBM) of young rats (3 months) and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500 × 10(3)/μL) and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions.

Figure 1

Inverted microscope photomicrograph shows morphological characteristic of MSCs (spindle shape) derived from rat bone marrow in passage 3. Scale bar: 20 μm.

Figure 2

Flow cytometry analysis of CD 105, CD 90, and CD 44 in rat MSCs. Results represent three independent experiments.

Figure 3

Comparisons of the acquisition performance on the Morris water maze task among the three groups. The results are the mean swimming time traveled per trial toward the platform. The mean values of the 16 trials for 4 days for each group are shown. Repeated measures of ANOVA for the swimming time among the groups were followed by Tukey's test. *P < 0.05 and **P < 0.01 as compared with the corresponding data from the impaired +PBS group. Performance was assessed two months after the treatments.

Figure 4

Comparisons of the retention performance on the Morris water maze task among the three groups two months after the treatments (unimapaired, impaired + PBS, impaired + MSCs). The mean values of the probe test for each group are shown. One-way ANOVA for the swimming time among the groups was followed by Tukey's test. *P < 0.05 as compared with the corresponding data from the impaired + PBS group.

Figure 5

Comparisons of the acquisition performance on the Morris water maze task among the three groups of the Ibo-lesioned rats. The results are the mean latency time traveled per trial. The mean values of the 16 trials for 4 days for each group are shown. Repeated measures of ANOVA for the swimming time among the groups. *P < 0.05 and **P < 0.01 as compared with the corresponding data from the Ibo + PBS group.

Figure 6

Comparisons of the retention performance on the Morris water maze task among the three groups of the rats. The results are the mean percentage of latency time to the platform in the probe test. The mean values of the four trials for each group are shown. Mean of swimming time among the groups was analyzed using one-way ANOVA and post hoc Tukey's test. *P < 0.05 and **P < 0.01 as compared with the corresponding data of the Ibo + PBS group.

Figure 7

Example of computer tracking from probe trial (90 s duration). (a): “aged-impaired + PBS”; (b): “aged-impaired + MSCs”. The rat of “aged-impaired” swims in a concentric pattern.