Effects of AAV-proBDNF on hippocampal DCX positive cells and PSD-95 expression in Alzheimer's disease mice

Objective To explore the effects of lateral ventricle injection of recombinant adeno-associated virus-brain-derived neurotrophic factor precursor (AAV-proBDNF) on the hippocampal neurogenesis in APPswePS1dE9 transgenic mice (Alzheimer's disease, AD). Methods Fifteen APP/PS1 dE9 transgenic mice (5 months old) were randomly divided into normal control, empty vector control and AAV-proBDNF groups (n=5 in each group). Recombinant vectors of AAV-proBDNF (8×1010 v.g.) were stereotaxically delivered into the right lateral ventricle in the AAV-proBDNF group, and empty AAV vector and normal saline (4 μL) were given respectively to the mice from the empty vector control and normal control groups. Enzyme-linked immunosorbent assay was conducted to test the proBDNF level in the brain in 4 weeks after injection. The count of doublecortin (DCX) positive cells and the expression of postsynaptic density-95 (PSD-95) in the hippocampus were detected by immunohistochemical assay and Western blotting respectively. Results In 4 weeks after injection, the proBDNF level was significantly higher in the AAV-proBDNF group than the normal control group and the empty vector control group (P < 0.05). The number of DCX-positive cells in the hippocampus of AAV-proBDNF group (202.46±24.27) was significantly lower than that in the normal control group (382.26±37.58, P < 0.05) and empty vector control group (365.48±32.68, P < 0.05). In AAV-proBDNF group, the relative content of PSD-95 (0.62±0.05) was obviously lower than the normal control group (0.82±0.02, P < 0.05) and vector control group (0.86±0.07, P < 0.05). Conclusion Lateral ventricle injection of AAV-proBDNF can induce the expression of proBDNF in the brain of AD mice, and reduce the number of new neurons and synaptic plasticity in the hippocampus.