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Huprine X Attenuates The Neurotoxicity Induced by Kainic Acid, Especially Brain Inflammation
Author(s) -
Relat Júlia,
Pérez Belén,
Camps Pelayo,
MuñozTorrero Diego,
Badia Albert,
Victòria Clos M.
Publication year - 2018
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12852
Subject(s) - kainic acid , neurogenesis , neurotoxicity , neuroprotection , pharmacology , in vivo , cholinergic , agonist , acetylcholinesterase , chemistry , inflammation , receptor , endocrinology , medicine , neuroscience , biology , toxicity , biochemistry , glutamate receptor , microbiology and biotechnology , enzyme
Huprine X ( HX ) is a synthetic anticholinesterasic compound that exerts a potent inhibitory action on acetylcholinesterase ( AC hE) 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 (C57 BL /6) and transgenic (3xTg‐ AD , APP swe) 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 pA kt1, Bcl2, pGSK 3β, 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 AC h EI s, in general, to treat a number of diseases that course with both cognitive deficits and chronic inflammatory processes.