Single amyloid-beta injection exacerbates 4-aminopyridine-induced seizures and changes synaptic coupling in the hippocampus
Abstract
Accumulation of amyloid-beta (Aβ) in temporal lobe structures, including the hippocampus, is related to a variety of Alzheimer's disease symptoms and seems to be involved in the induction of neural network hyperexcitability and even seizures. Still, a direct evaluation of the pro-epileptogenic effects of Aβ in vivo, and of the underlying mechanisms, is missing. Thus, we tested whether the intracisternal injection of Aβ modulates 4-aminopyridine (4AP)-induced epileptiform activity, hippocampal network function, and its synaptic coupling. When tested 3 weeks after its administration, Aβ (but not its vehicle) reduces the latency for 4AP-induced seizures, increases the number of generalized seizures, exacerbates the time to fully recover from seizures, and favors seizure-induced death. These pro-epileptogenic effects of Aβ correlate with a reduction in the power of the spontaneous hippocampal network activity, involving all frequency bands in vivo and only the theta band (4-10 Hz) in vitro. The pro-epileptogenic effects of Aβ also correlate with a reduction of the Schaffer-collateral CA1 synaptic coupling in vitro, which is exacerbated by the sequential bath application of 4-AP and Aβ. In summary, Aβ produces long-lasting pro-epile...Continue Reading
References
The role of beta-amyloid protein in synaptic function: implications for Alzheimer's disease therapy.
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