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

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 no...

Full description

Saved in:
Bibliographic Details
Published in:Basic & clinical pharmacology & toxicology 2018-01, Vol.122 (1), p.94-103
Main Authors: Relat, Júlia, Pérez, Belén, Camps, Pelayo, Muñoz‐Torrero, Diego, Badia, Albert, Victòria Clos, M.
Format: Article
Language:English
Subjects:
Acetylcholine receptors
Acetylcholinesterase
Animal models
Apoptosis
Brain
Cognition
Cognitive ability
Damage prevention
Glial cells
Glial fibrillary acidic protein
Glial plasticity
Inflammation
Kainic acid
Neurogenesis
Neuronal-glial interactions
Neuroprotection
Neurotoxicity
Pretreatment
Receptors
Rodents
Synaptophysin
Transgenic mice
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1742-7835
1742-7843
DOI:10.1111/bcpt.12852