Amyloid beta 1-42 inhibits entorhinal cortex activity in the beta-gamma range: role of GSK-3.
Oscillatory activity in the entorhinal cortex has been associated with several cognitive functions. Accordingly, Alzheimer Disease-associated cognitive decline has been related to amyloid beta-induced disturbances in several of these oscillatory patterns. We have previously shown that acute application of amyloid beta inhibits the generation of slow frequency oscillations (7-20 Hz). In contrast, alterations in faster oscillations recorded in Alzheimer Disease-transgenic mice that over-express amyloid beta have been controversial. Since transgenic mice may produce complex responses due to compensatory mechanisms, we tested the effect of acute application of amyloid beta on fast oscillations (beta-gamma bursts) generated by entorhinal cortex slices in vitro in a Mg2+ -ree solution. We also explored the participation of the enzyme glycogen synthase kinase 3 (GSK-3) in this effect. Our results show that bath application of a clinically relevant concentration of amyloid beta (10 nM) activates GSK-3 and reduces the power of beta-gamma bursts in the entorhinal cortex. The reduction of beta-gamma bursts by amyloid beta is blocked by inhibiting GSK-3 either with lithium or with SB 216763. Our results suggest that amyloid beta-induced inhibition of entorhinal cortex beta-gamma activity involves GSK-3 activation, which may provide a molecular mechanism for amyloid beta-induced neural network disruption and support the use of GSK-3 inhibitors to treat Alzheimer Disease.
Departamento de Neurobiologia del Desarrollo y Neurofisiologia, Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Boulevard Juriquilla 3001, Queretaro, 76230, Mexico. jfpena@unam.mx
Fernando
F
Pena-Ortega
Angeles
A
Solis-Cisneros
Benito
B
Ordaz
Hugo
H
Balleza-Tapia
Juan
J
Javier Lopez-Guerrero
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D018728:Entorhinal Cortex / Q000187:drug effects* / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D055366:Synaptic Potentials / Q000187:drug effects* / Q000502:physiology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D038362:Glycogen Synthase Kinase 3