Preclinical
models
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.
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.
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.
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.
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.
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.