Tolfenamic Acid Prevents Amyloid β-induced Olfactory Bulb Dysfunction In Vivo

Abstract

Our data further support the use of tolfenamic acid to prevent amyloid beta-induced pathology and the early symptoms of Alzheimer Disease.

Sudden Intrabulbar Amyloid Increase Simultaneously Disrupts Olfactory Bulb Oscillations and Odor Detection

“…These alterations are reflected in population activity changes, which seem to underlie cognitive deterioration and other related symptoms in AD [8, 9, 12–16]. Similar alterations in network activity have been observed in the OB upon the acute or prolonged presence of oligomerized A β [17–19], which also induces alterations in olfaction [17–21]. Considering that various OB oscillatory activities have been closely linked to olfactory information processing [22–28], it is likely that the A β -induced alterations in OB activity contribute to olfactory dysfunction.…”

“…A β 1-42 and its inverse sequence, A β 42-1 , were obtained from American Peptide (Sunnyvale, CA). The oligomerization protocol was performed as previously described [14, 19]. Briefly, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) was added to solid A β 1-42 at a final peptide concentration of 1 mM and incubated for 60 min at room temperature.…”

“…Such solution was then diluted with F12 medium (F12m) to reach a final concentration of 100 μ M. This solution was incubated at 5°C for 24 h and then centrifuged at 14,000 rpm for 10 min in the cold. The supernatant containing the A β oligomers, monomers, and protofibrils ([14, 19]; Figure 1(d)) was collected and used for the experiments. The inverse sequence A β 42-1 was prepared with the same procedure.…”

Single amyloid‐beta injection exacerbates 4‐aminopyridine‐induced seizures and changes synaptic coupling in the hippocampus

“…This solution was incubated at 5°C for 24 hr. Finally, the solution was centrifuged at 14,000 rpm for 10 min in the cold, and the supernatant containing the Aβ oligomers, as well as monomers and protofibrils (Balleza‐Tapia et al, ; Cornejo‐Montes‐de‐Oca et al, ), was collected and used for the experiments.…”

“…Direct application of Aβ can disrupt spontaneous oscillatory network activity in vitro (Adaya‐Villanueva, Ordaz, Balleza‐Tapia, Márquez‐Ramos, & Peña‐Ortega, ; Balleza‐Tapia, Huanosta‐Gutiérrez, Márquez‐Ramos, Arias, & Peña, ; Gutiérrez‐Lerma, Ordaz, & Peña‐Ortega, ; Peña et al, ; Peña‐Ortega, Solis‐Cisneros, Ordaz, Balleza‐Tapia, & Javier, ) and in vivo (Colom et al, ; Cornejo‐Montes‐de‐Oca, Hernández‐Soto, Isla, Morado‐Urbina, & Peña‐Ortega, ; Peña‐Ortega & Bernal‐Pedraza, ; Villette et al, ). The cellular mechanisms involved in Aβ‐induced disruption of neural network activity comprise changes in synaptic transmission (Balleza‐Tapia et al, ; Mura et al, ; Peña et al, ; Salamone et al, ; Satoh et al, ) and in intrinsic neuronal properties (Chen, ; Hou, Cui, Yu, & Zhang, ; Mondragón‐Rodríguez, Gu, et al, ; Peña et al, ; Rovira, Arbez, & Mariani, ; Shankar & Walsh, ; Ye, Selkoe, & Hartley, ), which involve direct actions of Aβ on ion channels (Balleza‐Tapia et al, ; Chen, ; Hou et al, ; Rovira et al, ; Shankar & Walsh, ; Ye et al, ) and/or their modulation through the activation of intracellular transduction pathways (Ekinci, Malik, & Shea, ; Wildburger & Laezza, ; Zhu et al, ).…”