Early onset of hypersynchronous network activity and expression of a marker of chronic seizures in the Tg2576 mouse model of Alzheimer's disease.

Abstract

Cortical and hippocampal hypersynchrony of neuronal networks seems to be an early event in Alzheimer's disease pathogenesis. Many mouse models of the disease also present neuronal network hypersynchrony, as evidenced by higher susceptibility to pharmacologically-induced seizures, electroencephalographic seizures accompanied by spontaneous interictal spikes and expression of markers of chronic seizures such as neuropeptide Y ectopic expression in mossy fibers. This network hypersynchrony is thought to contribute to memory deficits, but whether it precedes the onset of memory deficits or not in mouse models remains unknown. The earliest memory impairments in the Tg2576 mouse model of Alzheimer's disease have been observed at 3 months of age. We thus assessed network hypersynchrony in Tg2576 and non-transgenic male mice at 1.5, 3 and 6 months of age. As soon as 1.5 months of age, Tg2576 mice presented higher seizure susceptibility to systemic injection of a GABAA receptor antagonist. They also displayed spontaneous interictal spikes on EEG recordings. Some Tg2576 mice presented hippocampal ectopic expression of neuropeptide Y which incidence seems to increase with age among the Tg2576 population. Our data reveal that network hypersynchrony appears very early in Tg2576 mice, before any demonstrated memory impairments.

• Authors: Charlotte Bezzina, Laure Verret, Cécile Juan, Jessica Remaud, Hélène Halley, Claire Rampon, Lionel Dahan
• Journal: PloS one (PLoS One) Vol. 10 Issue 3 Pg. e0119910 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25768013 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• GABA-A Receptor Antagonists
• Neuropeptide Y

Topics

• Age Factors
• Alzheimer Disease (complications, physiopathology)
• Analysis of Variance
• Animals
• Biomarkers (metabolism)
• Electroencephalography
• Electroencephalography Phase Synchronization (drug effects, physiology)
• GABA-A Receptor Antagonists (pharmacology)
• Immunohistochemistry
• Male
• Mice
• Mice, Transgenic
• Nerve Net (physiopathology)
• Neuropeptide Y (metabolism)
• Seizures (complications, metabolism, physiopathology)