Representative picture of a primary culture of cortical neurons immunolabeled with anti-MAP2 antibody

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

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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.

ALZHEIMER'S DISEASE

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Representative picture of a primary culture of dopaminergic neurons immunolabeled with anti-TH antibody

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)

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Primary culture of mesencephalic neurons with microglial cells

  • α-synuclein oligomers / protofibrils (neuroinflammation)

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

  • SH-SY5Y expressing mutated GBAL444P

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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.

 

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Representative picture of a primary culture of motorneurons immunolabeled with anti-MAP2 antibody

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

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

  • Glutamate injury

  • Amyloid-β1-42 peptide injuries

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Representative picture of a primary culture of gabaergic neurons doubly immunolabeled with anti-MAP2 and anti-GAD67 antibodiesbaergiques MAP2 rouge GAD6

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

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Representative picture of a primary coculture of total brain neurons and oligodendrocytes doulby immunolabeled with anti-MAP2 and anti-MAG antibodies

CENTRAL DEMYELINATION MULTIPLE SCLEROSIS

In vitro models

Co-culture of myelinating oligodendrocytes and central neurons​

  • Induced demyelination by : 

      - Cuprizone

      - LPS

      - INF-γ

  • Kinetic of myelin maturation

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In vivo models​

Currently under validation. Will be based on demyelinating effect of cuprizone.

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Representative picture of a primary culture of central neurons immunolabeled with anti-MAP2 antibody

ADRENOLEUKO DYSTROPHY

In vitro models

Primary culture of central neurons

  • Very Long Chain Fatty Acid injuries

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Primary culture of cortical neurons co-cultured with glial cells

  • Very Long Chain Fatty Acid injuries

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Representative picture of a primary coculture of total brain neurons and oligodendrocytes doubly immunolabeled with anti-MAP2 and anti-alpha synuclein antibodies

MULTIPLE SYSTEM ATROPHY

In vitro models

Co-culture of myelinating oligodendrocytes and central neurons

  • Rotenone Injury

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