Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic mice
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 tra...
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| Format: | Article |
| Language: | zho |
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Editorial Office of Journal of Third Military Medical University
2021-04-01
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| Series: | Di-san junyi daxue xuebao |
| Subjects: | |
| Online Access: | https://aammt.tmmu.edu.cn/Upload/rhtml/202011150.htm |
| _version_ | 1798028684703039488 |
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| author | XU Manyu ZAHNG Yuan YI Xu XU Zhiqiang |
| author_facet | XU Manyu ZAHNG Yuan YI Xu XU Zhiqiang |
| author_sort | XU Manyu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T19:13:33Z |
| format | Article |
| id | doaj.art-95dc80b815a44932a90f36dea460c38e |
| institution | Directory Open Access Journal |
| issn | 1000-5404 |
| language | zho |
| last_indexed | 2024-04-11T19:13:33Z |
| publishDate | 2021-04-01 |
| publisher | Editorial Office of Journal of Third Military Medical University |
| record_format | Article |
| series | Di-san junyi daxue xuebao |
| spelling | doaj.art-95dc80b815a44932a90f36dea460c38e2022-12-22T04:07:33ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042021-04-0143762963410.16016/j.1000-5404.202011150Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic miceXU Manyu0ZAHNG Yuan1YI Xu2XU Zhiqiang3Department of Neurology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China Department of Neurology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China Department of Neurology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China Department of Neurology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China 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.https://aammt.tmmu.edu.cn/Upload/rhtml/202011150.htmbrain-derived neurotrophic factor propeptidealzheimer's diseaselearning and memorypostsynaptic density protein 95 |
| spellingShingle | XU Manyu ZAHNG Yuan YI Xu XU Zhiqiang Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic mice Di-san junyi daxue xuebao brain-derived neurotrophic factor propeptide alzheimer's disease learning and memory postsynaptic density protein 95 |
| title | Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic mice |
| title_full | Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic mice |
| title_fullStr | Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic mice |
| title_full_unstemmed | Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic mice |
| title_short | Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic mice |
| title_sort | exogenetic over expression of pbdnf affects learning and memory in appsweps1de9 transgenic mice |
| topic | brain-derived neurotrophic factor propeptide alzheimer's disease learning and memory postsynaptic density protein 95 |
| url | https://aammt.tmmu.edu.cn/Upload/rhtml/202011150.htm |
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