Inhibitory neuronal activity can compensate for adverse effects of beta-amyloid in hippocampal neurons

Brain Research
R A Graf, S B Kater

Abstract

One of the most prominent effects of Alzheimer disease is the disruption of finely tuned neuronal circuitry of discrete brain regions associated with learning and memory. Results from the present study support a role for the intrinsic inhibitory component of neuronal circuitry in determining the magnitude of beta-amyloid peptide induced cell death in the highly vulnerable pyramidal neurons of the hippocampus. Previous efforts have mostly focused on direct effects on excitatory neurons. By contrast, less emphasis has been placed on addressing a role for the intrinsic inhibitory component of cell-cell interactions of neuronal networks in response to Abeta. The present study provides evidence demonstrating that blockage of the intrinsic inhibitory component between Abeta exposed neurons leads to destabilization of calcium homeostasis and exacerbated neuronal death compared to Abeta treated cultures. Neuronal electrical activity was first silenced by exposing cultures to tetrodotoxin (TTX; 100 nM) plus Abeta, followed by survival counts. Cell death, unexpectedly, did not significantly differ from Abeta-exposed neurons. The intrinsic inhibition in Abeta-exposed cultures was then pharmacologically removed with picrotoxin (40 microM) ...Continue Reading

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Citations

Mar 4, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hsueh-Cheng ChiangYi Zhong
Nov 23, 2012·The Journal of Comparative Neurology·Hanna WootzFrancisco J Alvarez
Oct 20, 2006·Nature·Jorge J PalopLennart Mucke
Jul 24, 2013·Trends in Neurosciences·Jason D WarrenMartin N Rossor

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