Philippe Colin | EPFL Graph Search

A ce jour Technicien spécialisé en expérimentation animal in vivo (rongeurs) à lEPFL dans le laboratoire d'étude de la neurodégénérescence (LEN) du Professeur Patrick Aebischer (suisse). Juillet 1995 à Contrat à durée indéterminée en qualité de Technicien spécialisé in vivo au Septembre 2001 laboratoire du Dr. Jacques MALLET (thérapie génique du système nerveux) France. Octobre 1990 à Contrat à durée déterminée en qualité dAdjoint Technique 2ème degré au CNRS de juillet 1995 Gif-sur-Yvette au laboratoire du Dr. Jacques MALLET en qualité de technicien dans léquipe du Dr. Philippe HORELLOU.

Anti-Aβ antibodies bound to neuritic plaques enhance microglia activity and mitigate tau pathology

Philippe Colin, Vanessa Laversenne, Bernard Schneider

The brain pathology of Alzheimer’s disease (AD) is characterized by the misfolding and aggregation of both the amyloid beta (Aβ) peptide and hyperphosphorylated forms of the tau protein. Initial Aβ deposition is considered to trigger a sequence of deleterious events contributing to tau pathology, neuroinflammation and ultimately causing the loss of synapses and neurons. To assess the effect of anti-Aβ immunization in this context, we generated a mouse model by overexpressing the human tau protein in the hippocampus of 5xFAD mice. Aβ plaque deposition combined with human tau overexpression leads to an array of pathological manifestations including the formation of tau-positive dystrophic neurites and accumulation of hyperphosphorylated tau at the level of neuritic plaques. Remarkably, the presence of human tau reduces microglial clustering in proximity to the Aβ plaques, which may affect the barrier role of microglia. In this mouse model, continuous administration of anti-Aβ antibodies enhances the clustering of microglial cells even in the presence of tau. Anti-Aβ immunization increases plaque compaction, reduces the spread of tau in the hippocampal formation and prevents the formation of tau-positive dystrophic neurites. However, the treatment does not significantly reduce tau-induced neurodegeneration in the dentate gyrus. These results highlight that anti-Aβ immunization is able to enhance microglial activity around neuritic plaques, mitigating part of the tau-induced pathological manifestations.

2020

Nano-imaging trace elements at organelle levels in substantia nigra overexpressing alpha-synuclein to model Parkinson's disease

Philippe Colin, Graham Knott, Bernard Schneider

Sub-cellular trace element quantifications of nano-heterogeneities in brain tissues offer unprecedented ways to explore at elemental level the interplay between cellular compartments in neurodegenerative pathologies. We designed a quasi-correlative method for analytical nanoimaging of the substantia nigra, based on transmission electron microscopy and synchrotron X-ray fluorescence. It combines ultrastructural identifications of cellular compartments and trace element nanoimaging near detection limits, for increased signal-to-noise ratios. Elemental composition of different organelles is compared to cytoplasmic and nuclear compartments in dopaminergic neurons of rat substantia nigra. They exhibit 150-460 ppm of Fe, with P/Zn/Fe-rich nucleoli in a P/S-depleted nuclear matrix and Ca-rich rough endoplasmic reticula. Cytoplasm analysis displays sub-micron Fe/S-rich granules, including lipofuscin. Following AAV-mediated overexpression of alpha -synuclein protein associated with Parkinson's disease, these granules shift towards higher Fe concentrations. This effect advocates for metal (Fe) dyshomeostasis in discrete cytoplasmic regions, illustrating the use of this method to explore neuronal dysfunction in brain diseases. Lemelle et al. describe the use of TEM and synchrotron X-ray fluorescence for quasi-correlative nanoimaging and sub-cellular trace element quantification of rat brain tissue. They further observe elemental (iron and sulfur) dyshomeostasis in cytoplasmic granules when overexpressing alpha -synuclein protein associated with Parkinson's disease, demonstrating the usefulness of this method to further explore dysfunctions at organelle levels in brain diseases.

NATURE PUBLISHING GROUP2020

In vivo neurochemical measurements in cerebral tissues using a droplet-based monitoring system

Arnaud Bertsch, Philippe Colin, Philippe Renaud, Bernard Schneider, Aurélien Thomas

Direct collection of extracellular fluid (ECF) plays a central role in the monitoring of neurological disorders. Current approaches using microdialysis catheters are however drastically limited in term of temporal resolution. Here we show a functional in vivo validation of a droplet collection system included at the tip of a neural probe. The system comprises an advanced droplet formation mechanism which enables the collection of neurochemicals present in the brain ECF at high-temporal resolution. The probe was implanted in a rat brain and could successfully collect fluid samples organized in a train of droplets. A microfabricated target plate compatible with most of the surface-based detection methods was specifically developed for sample analysis. The time-resolved brain-fluid samples are analyzed using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The results provide a time evolution picture of the cerebral tissues neurochemical composition for selected elements known for their involvement in neurodegenerative diseases.

Nature Publishing Group2017