Parallel recordings of treated (memantine, picrotoxin, A[beta] oligomers, rPrP, or A[beta] oligomers + rPrP) and untreated hippocampal slices from the same animal were performed using a customized electrophysiology setup.
Comparisons of mean levels of L-LTP in slices in a given genotype for three different pharmacological treatments (memantine, picrotoxin, and a[beta] oligomers + rPrP) were done by one-way ANOVA (Statistica).
Effects of A[beta] and rPrP on 4xHFS-Induced LTP in Ts65Dn-Derived Hippocampal Slices.
Furthermore, when slices were exposed to A[beta] (500 nM) mixed with rPrP (100 nM), this inhibition was suppressed (Figure 5(c)), which is reflected by the statistically significant treatment effect observed ([F.sub.(3,41)] = 4.31, p = 0.0099).
These molecules were (1) picrotoxin; (2) A[beta] oligomers; and (3) soluble rPrP.
This pharmacological survey of the properties of 4xHFS-induced CA1 E-LTP in Ts65Dn-derived hippocampal slices concluded with the investigation of the effects of A[beta] oligomers and soluble rPrP. The obvious reason to probe the effects of A[beta] oligomers on LTP induced by 4xHFS in Ts65Dn-derived slices was that the amyloid precursor protein gene, APP (which encodes the protein from which A[beta] peptides originate), is present in three copies in persons with DS and Ts65Dn mice.
We had two competing hypotheses in designing the experiments involving the effects of A[beta] oligomers and soluble rPrP on 4xHFS-induced CA1 E-LTP.
Shaking interval is a crucial factor in producing more reactive seeds via fragmentation of r[PrP.sup.Sc] polymers and in enhancing the interaction between rPrP and [PrP.sup.Sc] by promoting partial unfolding of rPrP [60, 61].
The effect of SDS on false-positive responses was associated with rPrP substrates in the RT-QuIC reactions [54,63].
In a recent report, full-length bank vole rPrP was suggested as an apparently universal substrate for RT-QuIC-based detection.
The RT-QuIC requires further improvement for a few issues, such as reduction of the invasiveness of sample collection, expansion of adequate samples used for assays, ease of sampling, maintenance of the least false-negative responses, abundant availability of appropriate rPrP, and standardization of criteria defining RT-QuIC responses and the experimental environment.
A set of RT-QuIC quadruple reactions was performed with mouse rPrP (89-231) and [PrP.sup.Sc] seeds from ScN2a cells diluted 5 x [10.sup.-4]-fold.