Figure 1.

The ability to discriminate novel objects is lost in prion-infected mice, but recovers when neuronal PrP^C is depleted, in parallel with reversal of pathological change. (A) Mice are allowed to explore two objects in an arena during the learning phase of the test; then, after a retention interval, they are exposed to a novel object (test phase). Time spent actively exploring the novel object compared to the familiar one is a measure of object recognition memory and is expressed as exploratory ratio. (B) Prion-infected tg37 (white bars) and NFH-Cre/tg37 mice (black bars) showed normal object recognition memory at 7 wpi, with preferential exploration of the novel object. This was significantly impaired in all mice by 8 wpi, but recovered in mice with Cre-mediated PrP depletion at 9 wpi. Recovery was sustained up to 30 wpi. *p < 0.05; **p < 0.01; ***p < 0.001 (Student's t test; 2-tails). Open arrow indicates onset of earliest signs of scrapie in tg37 mice (ss). Closed arrow indicates onset of Cre mediated knockout. (C) Haematoxylin and eosin stained sections of hippocampi from prion- infected tg37 and NFH-Cre/tg37 mice have normal appearance at 6 wpi (A and D). Spongiosis develops in all animals (B and E) by 8 wpi when memory is impaired, but by 10 wpi this has reversed in mice with Cre-mediated depletion (panel F), in parallel with recovery of novel object memory. Scale bar represents 160 um.