Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic mice

Autor: XU Manyu, ZAHNG Yuan, YI Xu, XU Zhiqiang
Jazyk: čínština
Rok vydání: 2021
Předmět:
Zdroj: Di-san junyi daxue xuebao, Vol 43, Iss 7, Pp 629-634 (2021)
Druh dokumentu: article
ISSN: 1000-5404
DOI: 10.16016/j.1000-5404.202011150
Popis: Objective To explore the effect and possible machanism of recombinant adeno-associated virus (rAAV) vector containing brain-derived neurotrophic factor propeptide (AAV-pBDNF) on learning and memory in APPswePS1dE9 transgenic mice (Alzheimer's disease, AD). Methods A total of 18 APPswePS1dE9 transgenic mice were randomly and equally divided into control group, AAV-pBDNF group and AAV-pBDNF+p75NTR antibody group. Recombinant AAV-pBDNF vector (2 μL, 1×1012 vg/mL) were stereotaxically injected into the right side of the hippocampus in AAV-pBDNF group, AAV-GFP (2 μL, 1×1012 vg/mL) into that of the control group, and same amount of AAV-pBDNF and p75NTR antibody (2 μL, 10 μg/mL) into that of the AAV-pBDNF+p75NTR antibody group. There were 6 mice in each group. Morris water maze test was performed in 4 weeks after hippocampal injection to detect the changes of learning and memory abilities in AD rats. Immunofluorescence assay was used to observe the transfection ofAAV-pBDNF in the brain. Western blotting was employed to measure the expression of postsynaptic density protein 95 (PSD-95) in the hippocampus. Results The results of Morris water maze showed that no significant difference was seen in the movement speed of each group (P > 0.05); the escape incubation period on day 5 in the control group and AAV-pBDNF+p75NTR antibody group was significantly shorter than that of day 1 (P < 0.05); similar result was seen in the pBDNF group though no statistical difference (P > 0.05); and less platforms were crossed in the AD mice of the pBDNF group than those in the other 2 groups on day 6 in space exploration experiment (P < 0.05). Immunofluorescence assay showed that after transfection, pBDNF was expressed in the neurons, but not glial cells in the hippocampus. Western blotting results indicated that the expression of PSD-95 was obviously lower in the AAV-pBDNF group than the other 2 groups (P < 0.05). Conclusion pBDNF inhibits the learning and memory abilities of AD mice by down-regulating hippocampal expression of PSD-95.
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