PropertyValue
?:abstract
  • BACKGROUND: Current therapies in Alzheimer\'s disease (AD), including Memantine, have proven to be only symptomatic but not curative nor disease-modifying. Fluoroethylnormemantine (FENM) is a structural analogue of Memantine, functionalized with a fluorine group that allowed its use as a positron emission tomography tracer. We here analyzed FENM neuroprotective potential in a pharmacological model of AD, in comparison to Memantine. METHODS: Swiss mice were treated intracerebroventricularly with aggregated Aß25-35 peptide and examined after one week in a battery of memory tests (spontaneous alternation; passive avoidance; object recognition; place learning in the water-maze; topographic memory in the Hamlet). Toxicity induced in the mouse hippocampus or cortex was analyzed biochemically or morphologically. RESULTS: Both Memantine and FENM showed symptomatic anti-amnesic effects in Aß25-35-treated mice. Interestingly, FENM was not amnesic when tested alone at 10 mg/kg, contrarily to Memantine. Drugs injected once-a-day prevented Aß25-35-induced memory deficits, oxidative stress (lipid peroxidation, cytochrome c release), inflammation (IL-6, TNFα increases; glial fibrillary acidic protein (GFAP) and Iba1 immunoreactivity in the hippocampus and cortex), and apoptosis and cell loss (Bax/Bcl-2 ratio; cell loss in the hippocampus CA1 area). However, FENM effects were more robust than observed with Memantine, with significant attenuations vs. the Aß25-35-treated group. CONCLUSIONS: FENM therefore appeared as a potent neuroprotective drug in an AD model, with a superior efficacy as compared with Memantine, and an absence of direct amnesic effect at higher doses. These results open the possibility to use the compound at more relevant dosages than the ones actually proposed in Memantine treatment for AD.
is ?:annotates of
?:creator
?:journal
  • Int._j._neuropsychopharmacol
?:license
  • unk
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:source
  • WHO
?:title
  • Anti-amnesic and neuroprotective effects of Fluoroethylnormemantine (FENM) in a pharmacological mouse model of Alzheimer\'s disease
?:type
?:who_covidence_id
  • #32977336
?:year
  • 2020

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