Enhanced Hippocampal Neurogenesis in APP/Ps1 Mouse Model of Alzheimer’s Disease After Implantation of VEGF-loaded PLGA Nanospheres
Abstract
During adult life, hippocampus is an important brain region involved in neurogenesis. The generation and cell death of newly generated neuronal cells in this region have critical roles in brain maintenance and alterations in these processes are seen in Alzheimer's disease (AD). For the purpose of carrying out a neuroregenerative strategy, we propose a novel approach based on the encapsulation of vascular endothelial growth factor (VEGF) in poly (lactic co-glycolic acid) (PLGA) biodegradable nanospheres (NS) administered by craniotomy to stimulate the proliferation of neuronal precursors in a transgenic mouse model of AD. VEGF loaded nanospheres were prepared by double emulsion solvent evaporation technique, obtaining 200 nm nanospheres with a biphasic release profile. After demonstrating their efficacy in the proliferation and differentiation of neuronal cell cultures, in vivo studies were carried out. 3 months after VEGF-NS were implanted directly into the cerebral cortex of APP/Ps1 mice, the determination of BrdU(+) cells in the whole hippocampal region and specifically in the dentate gyrus, demonstrated a significantly enhanced cellular proliferation in VEGF-NS treated group. These results were also confirmed showing an increased number of DCX(+) and NeuN(+) cells. Hence, PLGA-VEGF nanospheres may be a potential strategy to modulate proliferative neuronal progenitors in the hippocampal region, and therefore, provide new insight for future therapeutic approaches in AD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In APP/PS1 mouse model, VEGF-loaded PLGA nanospheres improved memory by activation of neuronal progenitor cells in hippocampal region.
“In the APP/PS1 mouse model for AD, mice administered vascular endothelial growth factor-loaded PLGA nanospheres demonstrated excellent improvements in memory by the activation of neuronal progenitor cells in the hippocampal region.107”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [107]
Cited by
Sorted by citations
Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles
Singh, A. P., Biswas, A., Shukla, A., & Maiti, P. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0068-3 · Cited by 645 · see citing works
“In the APP/PS1 mouse model for AD, mice administered vascular endothelial growth factor-loaded PLGA nanospheres demonstrated excellent improvements in memory by the activation of neuronal progenitor cells in the hippocampal region.(107) Nerve growth factor is essential for the survival of neurons and may be utilized a…”
BackgroundHuang, N., Lü, S., Liu, X., Zhu, J., Wang, Y., & Liu, R. (2017) · Oncotarget · doi:10.18632/oncotarget.20944 · Cited by 170 · see citing works
VEGF Signaling in Neurological Disorders
Shim, J. W., & Madsen, J. R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010275 · Cited by 149 · see citing works
“In the same mouse model of AD, VEGF loaded nanosphere has been shown to enhance hippocampal neurogenesis [26].”
BackgroundOuaamari, Y. E., den Bos, J. V., Willekens, B. M. P., Cools, N., & Wens, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043866 · Cited by 107 · see citing works
Gao, C., Chu, X., Gong, W., Zheng, J., Xie, X., Yang, M., Yang, M., Li, Z., Gao, C., & Yang, Y. (2020) · Journal of Nanobiotechnology · doi:10.1186/s12951-020-00626-1 · Cited by 93 · see citing works
RetractedOmidian, H., & Wilson, R. L. (2025) · Pharmaceuticals · doi:10.3390/ph18050631 · Cited by 83 · see citing works
“Tailoring molecular weight and additives like PEG and poloxamer allows optimization of drug kinetics across applications [3,10,12,164].”
Yue, Q., & Hoi, M. P. M. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.367832 · Cited by 77 · see citing works
Advances in Nanomedicine for the Treatment of Alzheimer’s and Parkinson’s Diseases
Hernando, S., Gartziandia, O., Herrán, E., Pedraz, J. L., Igartúa, M., & Hernández, R. M. (2016) · Nanomedicine · doi:10.2217/nnm-2016-0019 · Cited by 48 · see citing works
Self-citationKim, S., Lee, M., & Choi, Y. K. (2019) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2019.119 · Cited by 47 · see citing works
“VEGF upregulation through VEGF loaded nanosphere or transplantation of encapsulated VEGF-secreting cells improves cognitive impairment of APP/presenilin-1 (PS-1) mouse model of AD, suggesting that VEGF has beneficial role in AD (Spuch et al., 2010; Herran et al., 2015; Shim and Madsen, 2018).”
BackgroundAsaro, A., Carlo‐Spiewok, A., Malik, A. R., Rothe, M., Schipke, C. G., Peters, O., Heeren, J., & Willnow, T. E. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12121 · Cited by 37 · see citing works
The effects of peripheral hormone responses to exercise on adult hippocampal neurogenesis
Kraemer, R. R., & Kraemer, B. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1202349 · Cited by 41 · see citing works
Zhong, L., Liu, H., Zhang, W., Liu, X., Jiang, B., Fei, H., & Sun, Z. (2018) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2018.6860 · Cited by 34 · see citing works
“In APP/PS1 transgenic mice, the memory impairment and amyloid deposition appear at 4-6 months of age and progress in an age-dependent manner (31,32).”
BackgroundEllagic Acid: A Dietary-Derived Phenolic Compound for Drug Discovery in Mild Cognitive Impairment
Wang, W., Wang, S., Liu, Y., Wang, X., Nie, J., Meng, X., & Zhang, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.925855 · Cited by 33 · see citing works
Ping, S., Qiu, X., Kyle, M. M., Hughes, K., Longo, J. A., & Zhao, L. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104561 · Cited by 32 · see citing works
Reversal of ApoE4-Driven Brain Pathology by Vascular Endothelial Growth Factor Treatment
Salomon‐Zimri, S., Glat, M. J., Barhum, Y., Luz, I., Boehm‐Cagan, A., Liraz, O., Ben‐Zur, T., Offen, D., & Michaelson, D. M. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160182 · Cited by 30 · see citing works
“In view of the important role of VEGF in both the neuronal and vascular systems, and of its suggested therapeutic potential in AD [39], we presently examined the possibility that VEGF plays a role in meditating the brain’s pathological effects of apoE4 and the associated cognitive deficits.”
BackgroundBridel, C., Hoffmann, T., Meyer, A., Durieux‐Lu, S., Simmelink, M. J. A., Orth, M., Scheltens, P., Lues, I., & Teunissen, C. E. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0266-6 · Cited by 27 · see citing works
Delbreil, P., Rabanel, J., Banquy, X., & Brambilla, D. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114397 · Cited by 25 · see citing works
Villate-Beitia, I., Puras, G., Soto‐Sánchez, C., Agirre, M., Ojeda, E., Sesma, J. Z., Fernández, E., & Pedraz, J. L. (2017) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2017.02.016 · Cited by 22 · see citing works
Self-citationGuo, H., Xia, D., Liao, S., Niu, B., Tang, J., Hu, H., Qian, H., & Cao, B. (2018) · Neuroscience Research · doi:10.1016/j.neures.2018.04.003 · Cited by 21 · see citing works
Gao, L., Dongqing, W., Ren, J., Tan, X., Chen, J., Kong, Z., Nie, Y., & Yan, M. (2023) · Phytotherapy Research · doi:10.1002/ptr.8006 · Cited by 20 · see citing works
“Our research results showed that the behavioral abnormalities and cognitive disorders of APP/PS1 mice were consistent with the results of many previous reports (Charles et al., 2008; Herran et al., 2015).”
BackgroundResultZhang, Z.-X., Zhao, R., Wang, D., & Wang, A.-N. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.09.003 · Cited by 20 · see citing works
“As a model of AD, APP/PS1 transgenic mice share similarity with clinical AD patients in pathogenesis, pathology and symptoms (Zeng et al., 2016; Herran et al., 2015).”
Kim, H. S., Shin, S. M., Kim, S., Nam, Y., Yoo, A., & Moon, M. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1002281 · Cited by 14 · see citing works
“Implantation of VEGF through nanospheres effectively increased adult neurogenesis in APP/PS1 mice (Antequera et al., 2012; Herran et al., 2015).”
BackgroundBiodegradable Nanoparticles for Drug Delivery and Targeting
Wiwanitkit, V. (2019) · Springer eBooks · doi:10.1007/978-3-030-06115-9_9 · Cited by 16 · see citing works
Alzheimer's Disease: Status of Low‐Dimensional Nanotherapeutic Materials
Huang, D., Liao, W., Li, J., Chen, T., Wang, X., Zhao, R., Zhang, L., Yu, X., Zheng, D., & Luan, P. (2023) · Advanced Functional Materials · doi:10.1002/adfm.202302015 · Cited by 14 · see citing works
VEGF mimic peptides: Potential applications in central nervous system therapeutics
D’Andrea, L. D., Rosa, L. D., Vigliotti, C., & Cataldi, M. (2016) · European Journal of Molecular & Clinical Medicine · doi:10.1016/j.nhtm.2016.12.002 · Cited by 12 · see citing works
Li, P., Quan, W., Wang, Z., et al. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.616614 · Cited by 10 · see citing works
“Cell proliferation is enhanced during differentiation in SGL and SVZ in AD-linked APP transgenic mice (Jin et al., 2004a,b; Lopez-Toledano and Shelanski, 2004, 2007; Herran et al., 2015).”
BackgroundResultInfluentialWang, F., Feng, J., Yang, Y., Liu, J., Liu, M., Wang, Z., Pei, H., Wei, Y., & Li, H. (2018) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s175484 · Cited by 8 · see citing works
Duong, Q.-V., Kintzing, M. L., Kintzing, W. E., Abdallah, I., Brannen, A., & Kaddoumi, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061489 · Cited by 7 · see citing works
“Several studies demonstrated that VEGF has a positive effect against AD [27,39,40,50].”
BackgroundFactors Regulating Neurogenesis in the Adult Dentate Gyrus
Zhang, L., & Zhang, X.-H. (2018) · Hippocampus · doi:10.5772/intechopen.75631 · Cited by 4 · see citing works
“Moreover, delivery of VEGF via VEGF-secreted cells in microcapsules or VEGFloaded poly (lactic co-glycolic acid) nanospheres increased the proliferation of neuronal progenitors [118, 119].”
BackgroundNanotechnology Based Approaches for Neurodegenerative Disorders: Diagnosis and Treatment
Hernando, S., Herrán, E., Pedraz, J. L., Igartúa, M., & Hernández, R. M. (2017) · Springer eBooks · doi:10.1007/978-3-319-57696-1_3 · Cited by 4 · see citing works
Self-citationThe Strategies of Nanomaterials for Therapy
Du, Y., Wang, S., Li, F., & Ling, D. (2019) · Springer eBooks · doi:10.1007/978-981-13-8731-9_4 · Cited by 2 · see citing works
Obulesu, M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816412-9.00009-4
Role of Co-Block Polymers in the Treatment of Neurodegenerative Diseases
Kaur, S., Ghosh, S., Sharma, G., Mishra, J., Joshi, R., Bhatti, G. K., & Bhatti, J. S. (2023) · Springer eBooks · doi:10.1007/978-981-99-6917-3_6
Gao, C., Chu, X., Gong, W., Zheng, J., Xie, X., Wang, Y., Yang, M., Li, Z., Gao, C., & Yang, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12299411
Gao, C., Chu, X., Gong, W., Zheng, J., Xie, X., Wang, Y., Yang, M., Li, Z., Gao, C., & Yang, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12299405
- Authors
- Herran, E., Perez- Gonzalez, R., Igartua, M., Pedraz, J. L., Carro, E., & Hernandez, R. M.
- Venue
- Current Alzheimer Research
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2015-11-18
- Volume
- 12
- Issue
- 10
- Pages
- 932-940
- ISSN
- 1567-2050 (ISSN-L)
- OpenAlex
- W1883738065
- Cited by
- 35
- References
- 0
- Citations by year
- 2025: 1 · 2023: 6 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 4
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Alzheimer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, hippocampal neurogenesis, vascular endothelial growth factor, PLGA nanospheres, APP/PS1 mice, neuronal progenitor proliferation, dentate gyrus, biodegradable drug delivery, nerve regeneration
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Doublecortin Protein, Alzheimer Disease, Animals, Cells, Cultured, Cerebral Cortex, Disease Models, Animal, Drug Carriers, Drug Implants, Female, Hippocampus, Humans, Mice, Transgenic, Polyglycolic Acid, Amyloid beta-Protein Precursor, Rats, Wistar, Neuroprotective Agents, Lactic Acid, Vascular Endothelial Growth Factor A, Cell Proliferation, Presenilin-1, Nanospheres, Neurogenesis, Biodegradable Plastics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
