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Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain
Published on: October 3, 2012
Immunohistochemical expression of prion protein (PrPC) in the human forebrain during development
Homa Adle-Biassette1, Catherine Verney, Katell Peoc'h
1AP HP, Hôpital Bichat-Claude Bernard, Service d'Anatomie Pathologie, Université Paris 7, Faculté de Médecine Denis Diderot, Paris, France. homa.adle@bch.aphp.fr
Insights
The cellular prion protein (PrPC) is expressed in developing human brains, particularly in axons and synapses. This suggests PrPC plays a key role in axonal growth and early microglial cell development.
Area of Science:
- Neuroscience
- Developmental Biology
Background:
- The cellular prion protein (PrPC) is a ubiquitous protein primarily found in adult brain synapses.
- Its developmental expression patterns and functions remain incompletely understood.
Purpose of the Study:
- To investigate the spatiotemporal expression of PrPC in the developing human forebrain from fetal to perinatal stages.
- To elucidate the potential roles of PrPC in neuronal and microglial development.
Main Methods:
- Utilized monoclonal antibodies for PrPC detection.
- Employed double immunofluorescence and confocal microscopy.
- Colocalized PrPC with markers for neurons (MAP2, doublecortin), synapses (synaptophysin, GAP-43), and microglia (Iba1) and astrocytes (GFAP).
Main Results:
- PrPC immunoreactivity was present in axonal tracts and fascicles from the 11th week of gestation onwards.
- Synaptic PrPC expression increased during synaptogenesis.
- Microglial cells showed high PrPC expression at midgestation, decreasing by term, while neuronal PrPC expression increased, especially in ischemic regions.
- Choroid plexus, ependymal, and endothelial cells consistently expressed PrPC; astrocytes showed occasional immunoreactivity.
Conclusions:
- Early PrPC expression in axonal fields suggests a role in axonal growth during human brain development.
- PrPC may also be involved in the early development and function of microglial cells.
Abstract:
The cellular prion protein (PrPC) is a ubiquitous protein whose expression in the adult brain occurs mainly in synapses. We used monoclonal antibodies to study fetal and perinatal PrPC expression in the human forebrain. Double immunofluorescence and confocal microscopy with GFAP, Iba1, MAP2, doublecortin, synaptophysin, and GAP-43 were used to localize PrPC. PrPC immunoreactivity was observed in axonal tracts and fascicles from the 11th week to the end of gestation. Synapses expressed PrPC at increasing levels throughout synaptogenesis. At midgestation, a few PrPC-labeled neurons were detected in the cortical anlage and numerous ameboid and intermediate microglial cells were PrPC-positive. In contrast, at the end of gestation, microglial PrPC expression decreased to almost nothing, whereas neuronal PrPC expression increased, most notably in ischemic areas. In adults, PrPC immunoreactivity was restricted to the synaptic neuropil of the gray matter. At all ages, choroid plexus, ependymal, and endothelial cells were labeled, whereas astrocytes were only occasionally immunoreactive. In conclusion, the early expression of PrPC in the axonal field may suggest a specific role for this molecule in axonal growth during development. Moreover, PrPC may play a role in early microglial cell development.
