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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 original | Anglès |
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Pàgines (de-a) | 94-103 |
Revista | Basic and Clinical Pharmacology and Toxicology |
Volum | 122 |
Número | 1 |
DOIs | |
Estat de la publicació | Publicada - 1 de gen. 2018 |
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Efectos de los inhibidores de la acetilconinesterasa (huprina X y heterodimeros) en los procesos neurotoxicos y neurogénicos in vivo e in vitro: Palpel de las isoformas -S y -R de la AChE
Clos Guillen, M. V. (PI), Marutle, A. (Altres), Nordberg, A. (Altres), Badia Sancho, A. (Investigador/a), Darreh-Shori, T. (Investigador/a) & Pérez Fernández, B. (Investigador/a)
Ministerio de Ciencia e Innovación (MICINN)
1/01/10 → 31/12/12
Projecte: Projectes i Ajuts a la Recerca