Seizure susceptibility and epileptogenesis are decreased in transgenic rats overexpressing neuropeptide Y
Section snippets
Experimental animals
NPY transgenic rats (Sprague–Dawley rats, Department of Physiology, West Virginia University, Morgantown, WV, USA) were developed by pronuclear injection of fertilized oocytes with a 14-kb clone of the rat structural NPY gene (Michalkiewicz and Michalkiewicz, 2000). Incorporation of additional (five) copies of the NPY gene resulted in an average increase by 1.3–2.7-fold in NPY concentration in various tissues, including brain as assessed by radioimmunoassay (Michalkiewicz and Michalkiewicz, 2000
Kainate-induced seizures
Preliminary experiments showed that 0.3 μg kainate injected into the lateral ventricle was the lowest convulsant dose causing reproducible EEG seizure activity in 100% of the rats without mortality. Status epilepticus, as defined by behavioral stage 5 seizures and EEG seizures occurring without interruption for at least 30 min, occurred in 75% of rats. This dose of kainate induced degeneration mainly restricted to the CA3 area of the hippocampus, subiculum and layer III of the entorhinal cortex
Discussion
We showed that transgenic rats overexpressing NPY in CA1 pyramidal neurons are less susceptible to limbic seizures induced by kainate and to kindling epileptogenesis than their wild-type littermates.
The observation that NPY transgenic rats had a delayed kindling epileptogenesis is in agreement with pharmacological evidence showing that subchronic NPY infusion in the hippocampus retards kindling acquisition (Reibel et al., 2000). It is interesting to note that kindling progression is
Acknowledgements
This work was supported by NATO CGR.972956, HFSP RG0045/2000-B, the Austrian Scientific Research Funds and NIH HL57921.
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