Cellular prion protein-mediated hippocampal neuron axon elongation impairment involved in cognitive impairment induced by sleep deprivation

Abstract

Objective To investigate the effect of rapid eye movement (REM) sleep deprivation on spatial memory and hippocampal cellular prion protein (PrPC) expression and to explore the underlying mechanism of cognitive impairment induced by sleep deprivation. Methods Adult Sprague-Dawley rats were sorted by weight, randomly divided into three groups: the cage control (CC) group, the tank control (TC) group, and the sleep deprivation (SD) group. Rats were deprived of REM sleep for 72 h using the modified multiple platform method. The Morris water maze task was used to assess hippocampal-dependent spatial memory. After sleep deprivation, the rats were sacrificed and their brain tissue was analyzed for PrPC protein expression via Western blotting. Hippocampal neuron axon elongation was examined as well after lentivector-mediated RNA interference (RNAi) of PrPC in primary cultured rat hippocampal neurons. Results REM sleep deprivation for 72 h resulted in spatial memory impairment. The number of times of rats passing through the platform was decreased significantly in the SD group (3.17±0.95) compared with the CC (7.17±0.95) and TC (6.50±0.62) groups (Z=2.026 6, Z=2.026 6, P<0.05), the mean value of proximity to the platform (mm) was greater for rats of the SD group (711.74±33.99) compared to those of the CC (592.32±31.31) and TC (580.86±11.36) groups (Z=-2.001 6, Z=-2.482 0, P<0.05). REM sleep deprivation for 72 h resulted in reduced PrPC level in the hippocampus (0.33±0.10) compared with the CC (1.01±0.33) and TC (0.96±0.27) groups (Z=2.152 9, Z=2.152 9, P<0.05). In primary cultured hippocampal neurons, axon elongation (μm) was inhibited 7 days in infected neurons (326.28±12.53) compared with normal (555.00±30.43) or negative control (558.70±23.10) cells (Z=4.768 4, Z=4.877 0, P<0.05). Conclusion These findings suggest that PrPC-mediated hippocampal neuron axon elongation inhibition is probably involved in spatial memory impairment induced by sleep deprivation in rats. Key words: Sleep deprivation; Cognition disorders; Memory; PrPC proteins; Axons