Preclinical
models
Alzheimer's disease
IN VITRO models
Primary culture of cortical or hippocampal neurons co-cultured with glial cells (astrocytes and microglia):
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Amyloid-β1-42 peptide injuries (induced with oligomers of peptide, for information see Callizot et al., 2013)
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Acute or chronic injuries (microglia activation)
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Glutamate and NMDA injuries
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TNF-α injuries / microglia activation
IN VIVO models
Intra-hippocampal injection of amyloid β1-42 oligomers in aged mice.
Combines the toxicity of amyloid beta oligomers and advanced ageing. Our model mimics the main pathologies of AD: neurodegeneration, activation of pro-inflammatory response, long-term and short-term memory deficit.
Validated with Donepezil, drug indicated for AD.
Neuronal plasticity
IN VITRO models
Primary culture of hippocampal neurons:
Assessment of neuritogenisis, synaptogenesis, and branching points.
IN VIVO models
Assessment of cognitive function in aged mice.
Aged mice present with deficit in spatial memory and with lack of reactivity, compared to younger mice. We evaluate the effects of pharmacological agents on age-related cognitive impairments in senescent mice.
Parkinson's disease
IN VITRO models
Primary culture of mesencephalic neurons (dopaminergic neurons):
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Mitochondrial toxins (6-OHDA, MPP+, rotenone) (Callizot et al., 2019)
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Lysosomal toxin (CBE)
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α-synuclein / protofibrils (neurotoxicity)
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Combined toxicity of α-synuclein protofibrils and chronic lysosomal impairment (CBE)
Primary culture of mesencephalic neurons with microglial cells:
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α-synuclein oligomers / protofibrils (neuroinflammation)
Genetic model with point mutation (Crispr/Cas9) in SH-SY5Y cells:
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SH-SY5Y expressing mutated GBAL444P
IN VIVO models
Intra-nigral injection of alpha-synuclein fibrils and lysosomal impairment in aged mice.
Combines the toxicity of alpha-synuclein fibrils and chronic inhibition of GBA, a lysosomal protein, in aged mice.
Our model mimics the main pathologies of PD: loss of dopaminergic neurons in the substancia nigra, neuroinflammation, deficit in motor coordination and synucleinopathy.
Model validated with compounds in clinical trials.
Amyotrophic Lateral Sclerosis
IN VITRO models
Nerves/muscle co-culture. Human muscle fibers innervated by rat spinal cord (SC) explants:
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Glutamate injury
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Amyloid-β1-42 peptide injuries
Primary culture of motorneurons wild type and transgenic animals (SOD 1)
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Glutamate injury
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Amyloid-β1-42 peptide injuries
IN VIVO models
Sciatic nerve injury as an in vivo model to study motor axon regeneration and muscle reinnervation.
Regeneration of motor axons is studied by electromyography, function recovery and histology analysis of sciatic nerve and neuromuscular functions.
Stroke
IN VITRO models
Brain ischemia is a medical condition in which poor blood flow to the brain causes oxygen and glucose deprivation (OGD), both leading to cell death. Primary culture of cortical neurons is subjected to OGD.
Huntington's disease
IN VITRO models
Primary culture of mesencephalic neurons (spiny neurons, GAD positive neurons) co-cultured with glial cells (astrocytes and microglia)
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Glutamate injury
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Growth factor deprivation
Multiple Sclerosis
IN VITRO models
Co-culture of myelinating oligodendrocytes and central neurons
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Induced demyelination by :
- Cuprizone
- LPS
- IFN-γ
IN VIVO models
Currently under validation. Will be based on demyelinating effect of Cuprizone.
Central
myelination
IN VITRO models
Primary culture of central neurons and oligodendrocytes.
Kinetics of OPCs differentiation, OLs maturation and Myelination of axons.
Induced
Peripheral
Neuropathies
IN VITRO models
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Anti-mitotic agents (taxol, vincristine, cisplatin) on primary culture of sensory neurons, with or without differentiation of Schwann cells
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Forskolin-induced demyelination in primary co-culture of sensory neurons and Schwann cells
IN VIVO models
Currently under validation.
Nerve
crush
IN VIVO models
Sciatic nerve injury on mice to investigate peripheral nerve regeneration. Investigation of:
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Functional recovery
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Electromyography (EMG)
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Morphometric analysis of sciatic nerve
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NMJs
Adrenoleukodystrophy
IN VITRO models
Primary culture of central neurons
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Very Long Chain Fatty Acid injuries
Primary culture of cortical neurons co-cultured with glial cells
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Very Long Chain Fatty Acid injuries
Multiple
System
Atrophy
IN VITRO models
Primary culture of central neurons
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Very Long Chain Fatty Acid injuries
Primary culture of cortical neurons co-cultured with glial cells
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Very Long Chain Fatty Acid injuries
Lysosomal
storage
diseases
IN VITRO models
Primary culture of central neurons injured with specific toxins:
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Gaucher’s disease: primary mesencephalic neurons injured a GBA inhibitor (CBE)
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GM1 gangliosidosis: primary cortical neurons injured with a GLB1 inhibitor (hirsutine)
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Krabbe disease: primary cortical neurons and oligodendrocytes injured with psychosine
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Hurler syndrome: primary cortical neurons injured with an IDUA inhibitor
Culture of SH-SY5Y cell lines harboring point mutations:
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Gaucher’s disease: L444P mutation on GBA
Other models under development.