Preclinical
models

Alzheimer's disease

IN VITRO models

Primary culture of cortical or hippocampal neurons co-cultured with glial cells (astrocytes and microglia): 

  • Amyloid-β1-42 peptide injuries (induced with oligomers of peptide, for information see Callizot et al., 2013)

  • Acute or chronic injuries (microglia activation)

  • Glutamate and NMDA injuries

  • 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):

  • Mitochondrial toxins (6-OHDA, MPP+, rotenone) (Callizot et al., 2019)

  • Lysosomal toxin (CBE)

  • α-synuclein / protofibrils  (neurotoxicity)

  • Combined toxicity of α-synuclein protofibrils and chronic lysosomal impairment (CBE)

Primary culture of mesencephalic neurons with microglial cells:

  • α-synuclein oligomers / protofibrils (neuroinflammation)

Genetic model with point mutation (Crispr/Cas9) in SH-SY5Y cells:

  • 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:

  • Glutamate injury

  • Amyloid-β1-42 peptide injuries

Primary culture of motorneurons wild type and transgenic animals (SOD 1)

  • Glutamate injury

  • 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)

  • Glutamate injury

  • Growth factor deprivation

Multiple Sclerosis

IN VITRO models​

Co-culture of myelinating oligodendrocytes and central neurons​

  • 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​

  • Anti-mitotic agents (taxol, vincristine, cisplatin) on primary culture of sensory neurons, with or without differentiation of Schwann cells

  • 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:

  • Functional recovery

  • Electromyography (EMG)

  • Morphometric analysis of sciatic nerve

  • NMJs

Adrenoleukodystrophy

IN VITRO models​

 

Primary culture of central neurons

  • Very Long Chain Fatty Acid injuries

Primary culture of cortical neurons co-cultured with glial cells

  • Very Long Chain Fatty Acid injuries

Multiple

System

Atrophy

IN VITRO models​

 

Primary culture of central neurons

  • Very Long Chain Fatty Acid injuries

Primary culture of cortical neurons co-cultured with glial cells

  • Very Long Chain Fatty Acid injuries

Lysosomal

storage

diseases

IN VITRO models​

 

Primary culture of central neurons injured with specific toxins:

  • Gaucher’s disease: primary mesencephalic neurons injured a GBA inhibitor (CBE)

  • GM1 gangliosidosis: primary cortical neurons injured with a GLB1 inhibitor (hirsutine)

  • Krabbe disease: primary cortical neurons and oligodendrocytes injured with psychosine

  • Hurler syndrome: primary cortical neurons injured with an IDUA inhibitor

Culture of SH-SY5Y cell lines harboring point mutations:

  • Gaucher’s disease: L444P mutation on GBA

Other models under development.