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Tests related to Toxicity effects

The NEUROTOX PACKAGEthe right & the fast answer to any neuro-toxicological issue.
Evaluation of the absence of effects of 1 compound (at 2 concentrations) on 5 main CNS functions:

  • Spontaneous neuronal firing
  • Basal synaptic transmission
  • Short-Term synaptic plasticity (Paired-Pulse Facilitation)
  • Potentiation of Long-Term synaptic plasticity (Long-Term Potentiation)
  • Inhibition of Long-Term synaptic plasticity (Long-Term Depression)

WITH:

  • Multi-Electrode Array recordings
  • Mice or rats
  • Acute Hippocampal slices
  • 3 slices/concentration

1 week to get the results: effect or not effect

Any effect detected: further investigation proposal

 

 


Additional standardized assays :

Select the pathology Select the target Select the Pharma Ref.

Toxic effects

Target

Pharm. Ref.

Biology

Bibliography

Code

Name

PDF

Interaction with fast sodium channels or AP

Sodium channels

TTX and lidocaine

Action Potentials propagation.

- Egert U, Heck D, Aertsen A (2002). Exp Brain Res 142:268-274.
- Smith SL, Otis TS (2003). J Neurosci 23:367-372.
- Stett A, Egert U, Guenther E, Hofmann F, Meyer T, Nisch W, Haemmerle H (2003). Anal Bioanal Chem 377:486-495.

SAP-001

Spontaneous Action Potentials of Purkinje Neurons

Interaction with fast sodium channels or AP

Sodium channels

TTX

Action Potentials propagation

- Colmers WF, Lukowiak K, Pittman QJ (1988). J Neurosci 8:3827-3837.
- Devor, M. (2006), J. Pain, 7(1 Suppl 1), S31-S37
- King GL, Dingledine R, Giacchino JL, McNamara JO (1985). J Neurophysiol 54:1295-1304.

SAP-002

Evoked Spikes in the CA3/CA1 region

Modification of excitatory/ inhibitory neurotransmission weight

AMPA/kainate receptors

Receptors NBQX/CNQX

Glutamate-mediated neurotransmission

- Goldstein JM, Litwin LC (1993). Mol Chem Neuropathol 18:145-152.
- Namba T, Morimoto K, Sato K, Yamada N, Kuroda S (1994). Brain Res 638:36-44.
- Sheardown MJ (1993). Stroke 24:I146-147; discussion I153-144.

SST-001

Basal Synaptic Transmission (Schaeffer Collaterals stimulation)

Modification of short-term synaptic plasticity

Presynaptic receptors (GPCR)

Carbachol

Short-term pre-synaptic plasticity

- I wata N, Higuchi M, Saido TC (2005). Pharmacol Ther 108:129-148.
- Price CJ, Karayannis T, Pal BZ, Capogna M (2005). Neuropharmacology 49 Suppl 1:45-56.
- Zucker RS, Regehr WG (2002) Short-term synaptic plasticity. Annu Rev Physiol 64:355-405.

SST-002

Paired-Pulse Facilitation in CA1 region

Interaction with long-lasting plasticity potentiation

NMDA receptors

D-AP5 / MK801 / memantine

Long-term synaptic plasticity

- Artola A, von Frijtag JC, Fermont PC, Gispen WH, Schrama LH, Kamal A, Spruijt BM (2006). Eur J Neurosci 23:261-272.
- Chen L, Miyamoto Y, Furuya K, Dai XN, Mori N, Sokabe M (2006). Neuropharmacology 51:659-670.
- Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton AA, Sacktor TC (2006). Science 313:1141-1144.
- Malenka, RC & Nicoll, RA (1999), Science, 285, 1870-1874.
- Rioult-Pedotti M-S, Friedman D and Donoghue JP (2006), Science, 290, 533-536.

SST-003

Long-Term Potentiation in CA1 region (100 Hz protocol)

Interaction with long-lasting plasticity depression

NMDA receptors

D-AP5

Long-term synaptic plasticity

- Artola A, von Frijtag JC, Fermont PC, Gispen WH, Schrama LH, Kamal A, Spruijt BM (2006). Eur J Neurosci 23:261-272.
- Kemp A, Manahan-Vaughan D (2007). Trends Neurosci 30:111-118.
- Yang J, Han H, Cao J, Li L, Xu L (2006). Hippocampus 16:431-436.

SST-004

Long-Term Depression in CA1 region (1 Hz protocol)

Interaction with long-lasting plasticity potentiation

GluR5-Containing Kainate receptors

On going

Long-Term synaptic plasticity

- Bortolotto ZA, Lauri S, Isaac JT, Collingridge GL (2003). Philos Trans R Soc Lond B Biol Sci 358:657-666.
- Bortolotto ZA, Clarke VR, Delany CM, Parry MC, Smolders I, Vignes M, Ho KH, Miu P, Brinton BT, Fantaske R, Ogden A, Gates M, Ornstein PL, Lodge D, Bleakman D, Collingridge GL (1999). Nature 402:297-301.
- More JC, Nistico R, Dolman NP, Clarke VR, Alt AJ, Ogden AM, Buelens FP, Troop HM, Kelland EE, Pilato F, Bleakman D, Bortolotto ZA, Collingridge GL, Jane DE (2004). Neuropharmacology 47:46-64.

SST-005

Long-Term Potentiation in CA3 region (100 Hz protocol)

Modification of CA1 neurons excitability/pro-convulsive properties

NA

Kainate & Carbamazepine

CA1 pyramidal neurons spontaneous activity

- Day IP, Goudie J, Nishiki K, Williams PD (1995). Toxicol Lett. Apr;76(3):239-43.
- Easter A, Bell ME, Damewood JR Jr, Redfern WS, Valentin JP, Winter MJ, Fonck C, Bialecki RA. (2009). Drug Discov Today.Sep;14(17-18):876-84. Jun 21. Review.
- Ketelaars SO, Gorter JA, van Vliet EA, Lopes da Silva FH, Wadman WJ. (2001). Neuroscience. 105(1):109-20.

SAP-003

Characterization of pro- or anti-convulsive properties

 

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