NR treatment enhances NAD+ and PGC-1α expression

Because the increase in NAD+ has been associated with the promotion of PGC-1α expression in various tissues, we further explored whether the treatment with NR could have any effects on PGC-1α expression and further affect the Aβ levels. Indeed, our quantitative RT-PCR analysis in the brain samples from the mice of NR-treated and control groups showed NR significantly increased the PGC-1α gene expression compared with the untreated group, p < 0.05 (Fig. 1C). One of the important roles of PGC-1α has been reported to be reduction of Aβ burden, thus we further tested the Aβ levels in these mice. Consistent with the increase in the PGC-1α expression, the Aβ levels are significantly decreased in the groups treated with NR (Fig. 1D).

NR improves synaptic plasticity in Tg2576 mice

Because NR treatment improves cognitive function, we next used electrophysiological recording to study if NR has effects on synaptic plasticity in hippocampal CA1 region, reflected by LTP. We found there was no difference in the input-output curves generated using the field excitatory postsynaptic potential versus stimulus intensity between the NR treatment and control Tg2576 mice (Fig. 2A). For the LTP, after a 60-minute NR treatment (20 µM), the responses were significantly increased, and were 224 ± 15% at 120 minutes of the theta-burst stimuli, and in the control mice, the response were 164 ± 12% (Fig. 2B) (n = 8 slices; p < 0.05). The NR perfusion in this condition does not affect the input-output curve, nor the LTP levels in WT mice (Fig. 2C and D); p > 0.05.