Title:Tolfenamic Acid Prevents Amyloid β-induced Olfactory Bulb Dysfunction In Vivo
Volume: 15
Issue: 8
Author(s): José M. Cornejo-Montes-de-Oca, Rebeca Hernández-Soto, Arturo G. Isla, Carlos E. Morado-Urbina and Fernando Peña-Ortega*
Affiliation:
- Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Qro., 76230,Mexico
Keywords:
Amyloid-β protein, olfaction, habituation, network activity, phosphorylation, tolefenmic acid.
Abstract: Background: Amyloid beta inhibits olfactory bulb function. The mechanisms involved in this
effect must include alterations in network excitability, inflammation and the activation of different
transduction pathways. Thus, here we tested whether tolfenamic acid, a drug that modulates several of
these pathological processes, could prevent amyloid beta-induced olfactory bulb dysfunction.
Objective: To test whether tolfenamic acid prevents amyloid beta-induced alterations in olfactory bulb
network function, olfaction and GSK3β activity.
Method: The protective effects of tolfenamic acid against amyloid beta-induced population activity inhibition
were tested in olfactory bulb slices from adult mice, while tolfenamic acid and amyloid beta
were bath-applied. We also tested the effects of amyloid-beta in slices obtained from animals pre-treated
chronically (21 days) with tolfenamic acid. The effects of amyloid beta micro-injected into the olfactory
bulbs were also tested, after two weeks, on olfactory bulb population activity and olfaction in control
and tolfenamic acid chronically treated animals. Olfaction was assessed with the odor-avoidance and the
habituation/cross-habituation tests. GSK3β activation was evaluated with Western-blot.
Results: Acute bath application of tolfenamic acid does not prevent amyloid beta-induced inhibition of
olfactory bulb network activity in vitro. In contrast, chronic treatment with tolfenamic acid renders the
olfactory bulb resistant to amyloid beta-induced network activity inhibition in vitro and in vivo, which
correlates with the inhibition of GSK3β activation and the protection against amyloid beta-induced olfactory
dysfunction.
Conclusion: Our data further support the use of tolfenamic acid to prevent amyloid beta-induced pathology
and the early symptoms of Alzheimer Disease.
