ROCK/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo
Open accessAbstract
The role of microglial motility in the context of adult neurodegeneration is poorly understood. In the present work, we investigated the microanatomical details of microglia-neuron interactions in an experimental mouse model of Parkinson's disease following the intraperitoneal injection of MPTP. The specific intoxication of dopaminergic neurons induces the cellular polarization of microglia, leading to the formation of body-to-body neuron-glia contacts, called gliapses, which precede neuron elimination. Inhibiting ROCK/Cdc42-mediated microglial motility in vivo blocks the activating features of microglia, such as increased cell size and number of filopodia and diminishes their phagocyting/secreting domains, as the reduction of the Golgi apparatus and the number of microglia-neuron contacts has shown. High-resolution confocal images and three-dimensional rendering demonstrate that microglia engulf entire neurons at one-to-one ratio, and the microglial cell body participates in the formation of the phagocytic cup, engulfing and eliminating neurons in areas of dopaminergic degeneration in adult mammals.
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The neuroprotective effect of ROCK inhibition in MPTP models is attributed to inhibition of the MPTP-induced microglial inflammatory response and to a direct protective effect on the dopaminergic neuritic network in vitro and the striatal axonal innervation in vivo.
“The neuroprotective effect was attributed to inhibition of the MPTP-induced microglial inflammatory response [171,173,174] and to a direct protective effect on the dopaminergic neuritic network in vitro and the striatal axonal innervation in vivo [172,174].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [171]
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- Authors
- Barcia, C., Ros, C. M., Annese, V., Carrillo-de Sauvage, M. A., Ros-Bernal, F., Gómez, A., Yuste, J. E., Campuzano, C. M., de Pablos, V., Fernandez-Villalba, E., & Herrero, M. T.
- Affiliations
- Universidad de Murcia (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Corresponding author
- Barcia, Carlos
- Venue
- Scientific Reports
- Published
- 2012-11-08
- Volume
- 2
- Issue
- 1
- Pages
- 809-809
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC3492875
- OpenAlex
- W2088987148
- Cited by
- 150
- References
- 7
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 12 · 2023: 9 · 2022: 10 · 2021: 10 · 2020: 17 · 2019: 9 · 2018: 13 · 2017: 8 · 2016: 14 · 2015: 13 · 2014: 10 · 2013: 7
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Repositori UJI (Universitat Jaume I) (submittedVersion, public-domain)
- Funders
- Universidad de Murcia
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (SAF2007-062262)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- microglial motility, microglial phagocytosis, dopaminergic neuron loss, Parkinson's disease, MPTP, rocks, Cdc42, microglial polarization, Golgi apparatus, phagocytic cup, neurodegeneration
- MeSH terms
- Animals, Golgi Apparatus, Mice, Inbred C57BL, Actin Cytoskeleton, Phagocytosis, Microglia, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, MPTP Poisoning, cdc42 GTP-Binding Protein, Cell Size, Mice, rho-Associated Kinases, Dopaminergic Neurons
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