[Effects of transplanted neural stem cells on synaptogenesis in APP/PS1 mice]

To explore the effects of transplanted neural stem cells (NSCs) on synaptogenesis in an Alzheimer' disease (AD) murine model and related mechanism.

Twenty 9-month-old APP/PS1 double transgenic mice were randomly divided into 2 groups. One group received NSCs transplantation (NSC group) in bilateral hippocampi while another group received an equal volume of 0.01 mol/L phosphate buffer saline (PBS group) as a negative control group. Ten wild-type mice were selected as the positive control group (WT group) without any treatment. After 8-week transplantation, the expressions of synaptophysin (SYN) and growth associated protein-43 (GAP-43) proteins in hippocampal areas were analyzed by immunofluorescence and Western blot. The number and structure of synapses in transplanted regions were observed by electron microscopy.

(1) Immunofluorescence staining showed that NSC-induced neurons highly expressed SYN and GAP-43 at the protein levels; (2) the expression of SYN and GAP-43 significantly increased in the NSC group versus the PBS group (F = 58.367, P < 0.01; F = 75.296, P < 0.01). No difference existed in the SYN level between NSC and WT groups (P > 0.05). However, the GAP-43 expression was significantly higher than that of the WT group (P < 0.01); (3) ultrastructure showed that the number of synapses in the NSC group with normal morphology (12.1 ± 2.1) increased than that in the PBS group (6.5 ± 2.2) (F = 15.981, P < 0.01). No difference existed between NSC and WT groups (11.0 ± 1.4) (P > 0.05).

NSC-induced neurons increase the number of synapses by an up-regulation of synaptic proteins, SYN and GAP-43. Thus synaptogenesis may be a key factor in improving the symptom of AD mice.