Neuroprotective effect of the alpha 7 nicotinic receptor agonist PHA 543613 in an in vivo excitotoxic adult rat model

Neuroscience
Laura Foucault-FruchardDaniel Antier

Abstract

Neuroinflammation is a key component of the pathophysiology of neurodegenerative diseases. The link between nicotine intake and positive outcome has been established, suggesting a role played by nicotinic receptors (nAChRs), especially α7nAChRs. The objective of this study was to evaluate the potential dose effects of PHA 543613 on neuron survival and striatal microglial activation in a rat model of brain excitotoxicity. A preliminary study was performed in vitro to confirm PHA 543613 agonist properties on α7nAChRs. Rats were lesioned in the right striatum with quinolinic acid (QA) and received either vehicle or PHA 543613 at 6 or 12mg/kg twice a day until sacrifice at Day 4 post-lesion. We first compared the translocator protein quantitative autoradiography in QA-lesioned brains with [3H]DPA-714 and [3H]PK-11195. The effects of PHA 543613 on microglial activation and neuronal survival were then evaluated through [3H]DPA-714 binding and immunofluorescence staining (Ox-42, NeuN) on adjacent brain sections. We demonstrated that [3H]DPA-714 provides a better signal-to-noise ratio than [3H]PK-11195. Furthermore, we showed that repeated PHA 543613 administration at a dose of 12mg/kg to QA-lesioned rats significantly protected neuron...Continue Reading

Citations

Nov 2, 2017·Neural Regeneration Research·Laura Foucault-Fruchard, Daniel Antier
Mar 27, 2020·European Journal of Nuclear Medicine and Molecular Imaging·Catriona WimberleyIrène Buvat
Nov 11, 2020·Neuroscience and Biobehavioral Reviews·Salar VaseghiMohammad-Reza Zarrindast
Jun 6, 2021·Journal of Labelled Compounds & Radiopharmaceuticals·Agnieszka ZakJohnny Vercouillie

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