Ultrasound Combined With Microbubbles Loading BDNF Retrovirus to Open Blood–Brain Barrier for Treatment of Alzheimer’s Disease
Background: Brain-derived nerve growth factor (BDNF) is a promising effective target for the treatment of Alzheimer’s disease (AD). BDNF, which has a high molecular weight, has difficulty in crossing the blood–brain barrier (BBB). The study aimed to prepare microbubbles loading brain-derived nerve g...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.615104/full |
| _version_ | 1819159171090612224 |
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| author | Feng Wang Feng Wang Xi-Xi Wei Lian-Sheng Chang Lei Dong Yong-Ling Wang Na-Na Li |
| author_facet | Feng Wang Feng Wang Xi-Xi Wei Lian-Sheng Chang Lei Dong Yong-Ling Wang Na-Na Li |
| author_sort | Feng Wang |
| collection | DOAJ |
| description | Background: Brain-derived nerve growth factor (BDNF) is a promising effective target for the treatment of Alzheimer’s disease (AD). BDNF, which has a high molecular weight, has difficulty in crossing the blood–brain barrier (BBB). The study aimed to prepare microbubbles loading brain-derived nerve growth factor (BDNF) retrovirus (MpLXSN-BDNF), to verify the characteristics of the microbubbles, and to study the therapeutic effect of the microbubbles combined with ultrasound on the opening of the blood–brain barrier in an AD rat model.Methods: 32 adult male SD rats were randomly divided into four groups: control group, ultrasound + pLXSN-EGFP microbubble group (U + MpLXSN-BDNF), ultrasound + pLXSN-BDNF microbubble group, and ultrasound + microbubble + pLXSN-BDNF virus group (U + MpLXSN-BDNF), with eight rats in each group. At the same time, the left hippocampus of rats was irradiated with low-frequency focused ultrasound guided by MRI to open the blood–brain barrier (BBB). The effects of BDNF overexpression on AD rats were evaluated behaviorally before and 1 month after the treatment. The number of acetylcholinesterase (ChAT)-positive cells and the content of acetylcholine (ACh) in brain tissues were determined by immunohistochemistry and high-performance liquid chromatography (HPLC), respectively. IF staining of synaptic spines and Western blot of synaptophysin presented herein detected synaptic density recovery.Results: Signal intensity enhancement at the BBB disruption sites could be observed on the MR images. The behavioral evaluation showed that the times of crossing the original platform in the U + MpLXSN-BDNF group increased significantly after treatment. Immunohistochemistry and HPLC revealed that the number of ChAT-positive neurons and the contents of ACh in the brain were significantly decreased in the treated groups compared with the controls. IF staining of synaptic spines and Western blot data of synaptophysin showed that the U + MpLXSN-BDNF group can recover the synaptic loss better by BDNF supplementation than the other treatment groups.Conclusion: Ultrasound combined with viral microbubbles carrying BDNF can increase the transfection efficiency of brain neurons, promote the high expression of exogenous gene BDNF, and play a therapeutic role in the AD model rats. |
| first_indexed | 2024-12-22T16:36:18Z |
| format | Article |
| id | doaj.art-1b95a60c22ac43f2bfc162fa3aec129c |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T16:36:18Z |
| publishDate | 2021-03-01 |
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| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-1b95a60c22ac43f2bfc162fa3aec129c2022-12-21T18:19:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-03-011210.3389/fphar.2021.615104615104Ultrasound Combined With Microbubbles Loading BDNF Retrovirus to Open Blood–Brain Barrier for Treatment of Alzheimer’s DiseaseFeng Wang0Feng Wang1Xi-Xi Wei2Lian-Sheng Chang3Lei Dong4Yong-Ling Wang5Na-Na Li6Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, ChinaHenan Key Laboratory of Neurorestoratology (The First Affiliated Hospital of Xinxiang Medical University), Xinxiang, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, ChinaDepartment of Histology and Embryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, ChinaHenan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, ChinaHenan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, ChinaBackground: Brain-derived nerve growth factor (BDNF) is a promising effective target for the treatment of Alzheimer’s disease (AD). BDNF, which has a high molecular weight, has difficulty in crossing the blood–brain barrier (BBB). The study aimed to prepare microbubbles loading brain-derived nerve growth factor (BDNF) retrovirus (MpLXSN-BDNF), to verify the characteristics of the microbubbles, and to study the therapeutic effect of the microbubbles combined with ultrasound on the opening of the blood–brain barrier in an AD rat model.Methods: 32 adult male SD rats were randomly divided into four groups: control group, ultrasound + pLXSN-EGFP microbubble group (U + MpLXSN-BDNF), ultrasound + pLXSN-BDNF microbubble group, and ultrasound + microbubble + pLXSN-BDNF virus group (U + MpLXSN-BDNF), with eight rats in each group. At the same time, the left hippocampus of rats was irradiated with low-frequency focused ultrasound guided by MRI to open the blood–brain barrier (BBB). The effects of BDNF overexpression on AD rats were evaluated behaviorally before and 1 month after the treatment. The number of acetylcholinesterase (ChAT)-positive cells and the content of acetylcholine (ACh) in brain tissues were determined by immunohistochemistry and high-performance liquid chromatography (HPLC), respectively. IF staining of synaptic spines and Western blot of synaptophysin presented herein detected synaptic density recovery.Results: Signal intensity enhancement at the BBB disruption sites could be observed on the MR images. The behavioral evaluation showed that the times of crossing the original platform in the U + MpLXSN-BDNF group increased significantly after treatment. Immunohistochemistry and HPLC revealed that the number of ChAT-positive neurons and the contents of ACh in the brain were significantly decreased in the treated groups compared with the controls. IF staining of synaptic spines and Western blot data of synaptophysin showed that the U + MpLXSN-BDNF group can recover the synaptic loss better by BDNF supplementation than the other treatment groups.Conclusion: Ultrasound combined with viral microbubbles carrying BDNF can increase the transfection efficiency of brain neurons, promote the high expression of exogenous gene BDNF, and play a therapeutic role in the AD model rats.https://www.frontiersin.org/articles/10.3389/fphar.2021.615104/fullcationic microbubblesAlzheimer’s diseaseretrovirusBDNFblood-brain barrier |
| spellingShingle | Feng Wang Feng Wang Xi-Xi Wei Lian-Sheng Chang Lei Dong Yong-Ling Wang Na-Na Li Ultrasound Combined With Microbubbles Loading BDNF Retrovirus to Open Blood–Brain Barrier for Treatment of Alzheimer’s Disease Frontiers in Pharmacology cationic microbubbles Alzheimer’s disease retrovirus BDNF blood-brain barrier |
| title | Ultrasound Combined With Microbubbles Loading BDNF Retrovirus to Open Blood–Brain Barrier for Treatment of Alzheimer’s Disease |
| title_full | Ultrasound Combined With Microbubbles Loading BDNF Retrovirus to Open Blood–Brain Barrier for Treatment of Alzheimer’s Disease |
| title_fullStr | Ultrasound Combined With Microbubbles Loading BDNF Retrovirus to Open Blood–Brain Barrier for Treatment of Alzheimer’s Disease |
| title_full_unstemmed | Ultrasound Combined With Microbubbles Loading BDNF Retrovirus to Open Blood–Brain Barrier for Treatment of Alzheimer’s Disease |
| title_short | Ultrasound Combined With Microbubbles Loading BDNF Retrovirus to Open Blood–Brain Barrier for Treatment of Alzheimer’s Disease |
| title_sort | ultrasound combined with microbubbles loading bdnf retrovirus to open blood brain barrier for treatment of alzheimer s disease |
| topic | cationic microbubbles Alzheimer’s disease retrovirus BDNF blood-brain barrier |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.615104/full |
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