Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease
Open accessAbstract
Parkinson's disease (PD) is a neurodegenerative disease where the degeneration of the nigrostriatal pathway leads to specific motor deficits. There is an unmet medical need for regenerative treatments that stop or reverse disease progression. Several growth factors have been investigated in clinical trials to restore the dopaminergic nigrostriatal pathway damaged in PD. Platelet-derived growth factor-BB (PDGF-BB), a molecule that recruits pericytes to stabilize microvessels, was recently investigated in a phase-1 clinical trial, showing a dose-dependent increase in dopamine transporter binding in the putamen of PD patients. Interestingly, evidence is accumulating that PD is paralleled by microvascular changes, however, whether PDGF-BB modifies pericytes in PD is not known. Using a pericyte reporter mouse strain, we investigate the functional and restorative effect of PDGF-BB in a partial 6-hydroxydopamine medial forebrain bundle lesion mouse model of PD, and whether this restorative effect is accompanied by changes in pericyte features. We demonstrate that a 2-week treatment with PDGF-BB leads to behavioural recovery using several behavioural tests, and partially restores the nigrostriatal pathway. Interestingly, we find that pericytes are activated in the striatum of PD lesioned mice and that these changes are reversed by PDGF-BB treatment. The modulation of brain pericytes may contribute to the PDGF-BB-induced neurorestorative effects, PDGF-BB allowing for vascular stabilization in PD. Pericytes might be a new cell target of interest for future regenerative therapies.
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The damage generated by the stereotaxic injection itself could partially explain the discrepancy in pericyte changes between our findings and the previous results.
“the damage generated by the stereotaxic injection itself could partially explain the discrepancy in pericyte changes between our findings and the previous results [74]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity <i>via</i> AMPK/SOD2 Pathway (2023) · cites this paper as [74]
A notable increase in pericytes was observed in the lesioned striatum of 6-hydroxydopamine (6-OHDA)-induced PD mice.
“a notable increase in pericytes was observed in the lesioned striatum of 6-hydroxydopamine (6-OHDA)-induced PD mice [74]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity <i>via</i> AMPK/SOD2 Pathway (2023) · cites this paper as [74]
The presence of gut dysbacteriosis may also partly account for the discrepancy in pericyte-related findings between our study and that of Padel.
“the presence of gut dysbacteriosis may also partly account for the discrepancy in pericyte-related findings between our study and that of Padel [74]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity <i>via</i> AMPK/SOD2 Pathway (2023) · cites this paper as [74]
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Brain Pericytes As Mediators of Neuroinflammation
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- Authors
- Padel, T., Özen, I., Boix, J., Barbariga, M., Gaceb, A., Roth, M., & Paul, G.
- Affiliations
- Lund University (SE)
- Corresponding author
- Paul, Gesine
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 94
- Pages
- 95-105
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2415601235
- Cited by
- 70
- References
- 47
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 9 · 2023: 7 · 2022: 9 · 2021: 9 · 2020: 8 · 2019: 2 · 2018: 8 · 2017: 2 · 2016: 1
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Swedish Medical Research Council (K2012-61X-22095-01-4)
- European Union (279102)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- PDGF-BB, Parkinson's disease, pericytes, neurorestoration, 6-hydroxydopamine lesion, medial forebrain bundle, nigrostriatal pathway, striatum, regenerative therapy, microvascular changes, dopamine transporter
- MeSH terms
- Becaplermin, Animals, Corpus Striatum, Disease Models, Animal, Dopamine, Male, Medial Forebrain Bundle, Mice, Transgenic, Motor Activity, Parkinson Disease, Oxidopamine, Pericytes, Proto-Oncogene Proteins c-sis
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