Huprine X Attenuates The Neurotoxicity Induced by Kainic Acid, Especially Brain Inflammation

Júlia Relat, Belén Pérez, Pelayo Camps, Diego Muñoz-Torrero, Albert Badia, M. Victòria Clos

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© 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society) Huprine X (HX) is a synthetic anticholinesterasic compound that exerts a potent inhibitory action on acetylcholinesterase (AChE) activity, an agonist effect on cholinergic receptors, neuroprotective activity in different neurotoxicity models in vivo and in vitro and cognition enhancing effects in non-transgenic (C57BL/6) and transgenic (3xTg-AD, APPswe) mice. In this study, we assessed the ability of HX (0.8 mg/kg, 21 days) to prevent the damage induced by kainic acid (KA; 28 mg/kg) regarding apoptosis, glia reactivity and neurogenesis in mouse brain. KA administration significantly modified the levels of pAkt1, Bcl2, pGSK3β, p25/p35, increased the glial cell markers and reduced the neurogenesis process. We also observed that pre-treatment with HX significantly reduced the p25/p35 ratio and increased synaptophysin levels, which suggests a protective effect against apoptosis and an improvement of neuroplasticity. The increase in GFAP (88%) and Iba-1 (72%) induced by KA was totally prevented by HX pre-treatment, underlying a relevant anti-inflammatory action of the anticholinesterasic drug. Our findings highlight the potential of HX, in particular, and of AChEIs, in general, to treat a number of diseases that course with both cognitive deficits and chronic inflammatory processes.
Idioma originalAnglès
Pàgines (de-a)94-103
RevistaBasic and Clinical Pharmacology and Toxicology
Volum122
Número1
DOIs
Estat de la publicacióPublicada - 1 de gen. 2018

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