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ALZHEIMER'S DISEASE
β-AMYLOID-INDUCED NEUROTOXICITY
Model of β-AMYLOID-INDUCED NEUROTOXICITY
in rat HIPPOCAMPAL NEURONS
INTRODUCTION
Alzheimer disease (AD) is the most common cause of dementia. It is a neurodegenerative disease characterized by an extracellular accumulation of neurotoxic fibrillar amyloid beta peptide (Aβ). Intoxication of neuronal cultures with Aβ has been widely used to understand some of the mechanisms of cell death in AD and thus represents an instrumental in-vitro system to evaluate the efficiency of new drug candidate.
COMPOUND TESTING
Compound testing addresses the ability of test compounds to inhibit Aβ (1-40) - induced cell damage in hippocampal neuron cultures as assessed by:

- MTT assay
- LDH assay
Dose response curve of 2 batch of Aβ 1-40 on hippocampal neurons
Reduced cell viability (MTT assay) in hippocampal neuron culture in response to increasing concentration of Aβ 1-40. Peptide batch 1009415
Reduced cell viability (MTT assay) in hippocampal neuron culture in response to increasing concentration of Aβ 1-40. Peptide batch 1009501
Increased cell death (LDH assay) in hippocampal neurons in response to increasing doses of Aβ 1-40.

 *: significantly different as compared to control group. Peptide batch 1009415
Increased cell death (LDH assay) in hippocampal neurons in response to increasing doses of Aβ 1-40.

*: significantly different as compared to control group. Peptide batch 1009501
Neuroprotective effect of FGF and Resveratrol (pre/co-treatment) on hippocampal neurons damaged by Aβ 1-40
Prevention of Aβ 1-40 –induced neuronal injury by pretreatment with bFGF or by resveratrol as assessed by MTT assay in hippocampal cultures.

*: significantly different as compared to Aβ group.
Prevention of Aβ 1-40 –induced neuronal injury by bFGF or by resveratrol as assessed by MTT assay in hippocampal cultures. bFGF (or reseveratrol) is added to culture media at the same time as Aβ 1-40.

*: significantly different as compared to Aβ group.
REFERENCES
Resende R, Pereira C, Agostinho P, Vieira AP, Malva JO, Oliveira CR. Susceptibility of hippocampal neurons to Abeta peptide toxicity is associated with perturbation of Ca2+ homeostasis.
Brain Res. 2007 Apr 27;1143:11-21. Epub 2007 Jan 27.
Jarvis K, Assis-Nascimento P, Mudd LM, Montague JR. Beta-amyloid toxicity and reversal in embryonic rat septal neurons.
Neurosci Lett. 2007 Aug 23;423(3):184-8. Epub 2007 Aug 9.
Hirai K, Hayako H, Kato K, Miyamoto M. Idebenone protects hippocampal neurons against amyloid beta-peptide-induced neurotoxicity in rat primary cultures.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Nov;358(5):582-5.
Han YS, Zheng WH, Bastianetto S, Chabot JG, Quirion R. Neuroprotective effects of resveratrol against beta-amyloid-induced neurotoxicity in rat hippocampal neurons: involvement of protein kinase
C. Br J Pharmacol. 2004 Mar;141(6):997-1005.
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