NEUROSCIENCE CELL-BASED ASSAYS

CENTRAL NERVOUS SYSTEM

Porsolt offers models in all areas of psychopharmacology, epilepsy, sleep-wake, and neurodegenerative disorders. We are uniquely placed to offer a full range of CNS efficacy and safety pharmacology assessments, from basic models and regulatory tests, through the evaluation of abuse and dependence liability and proconvulsant risk using EEG.

NEUROSCIENCE CELL-BASED ASSAYS

Specific cell-based assays have been developed at Porsolt to support drug discovery projects addressing neurodevelopmental disorders, neurodegenerative diseases and neuroregeneration. Mostly based on primary neuronal cultures, our neuroscience assays are optimized for high-content screening. We offer to select and characterize potential neuroprotective, neurotrophic or neurotoxic drug compounds, and to determine their mechanism of action.

NEURITE OUTGROWTH ASSAYS

Primary cortical neurons are plated and treated or not with a test drug. Neuritic growth is then followed kinetically by phase contrast time-lapse imaging up to several days. Phase contrast images are segmented (segmentation masks) and treatment effect is then evaluated on the neuritic growth.

Neuritic growth in neural cell lines and primary neurons is a relevant readout to monitor neuronal health. As a result, different neurite outgrowth assays have been developed at Porsolt, allowing the screening and characterization of neuroprotective, neurodegenerative or neurotoxic compounds:

> Endpoint neurite outgrowth measurement performed by high-content imaging, enabling neuronal subpopulation studies (e.g. measurement of neuritic growth in the dopaminergic neuron population in in vitro models of Parkinson's disease)

> Kinetic neurite outgrowth monitoring to identify neuroactive or neurotoxic compounds

NEURONAL CELL SIGNALING ASSAYS

Alterations in signal transduction pathways have been reported in the etiopathology of many neurological disorders. We maintain a panel of cell-based assays to assess the impact of drug candidates on major cell signaling pathways:

> Calcium signaling assay

> ERK 1/2 phosphorylation assay

> CREB phosphorylation assay

> Prolactin release assay

> Glucocorticoid receptor translocation assay

NEURODEGENERATION-RELATED ASSAYS

To investigate the underlying mechanisms of neurodegeneration at the cellular level and characterize potential therapeutic compounds, we developed a range of robust cell-based assays addressing key pathological events found in neurodegenerative disorders:

> Neurite outgrowth impairment assay

> Neuronal  death assay

> Calcium homeostasis disruption assay

> Glutamate-induced excitotoxicity assay

> Mitochondrial dysfunction assay

> Oxidative stress assay

> Tau-hyperphosphorylation assay

> Gamma-secretase activity assay

> Neuronal autophagy assay

> Neuroinflammation assay

> Proteasome impairment assay