Upregulation of PP1 Expression in Hippocampus Impairs Long-term Spatial Memory in Rats

Abstract

Aims: Either down-regulation of protein kinases or up-regulation of protein phosphatases weakens the level of neuronal protein phosphorylation and affects the function of neuron. Low-function and/or low-content of protein phosphatases in the hippocampus neurons is proposed to be a possible causative factor to the impairment of spatial memory ability. We show here that upregulation of PP1(protein phosphatase1) expression in hippocampus correlates with the decline of the spatial-memory retention ability in rat brain. Study Design: In the present study, 30 adult Wistar rats were tested in a one trial step-down test to assess normal and impaired memory retention, examining protein phosphatases expression in their hippocampi and analysing both relationship. Place and Duration of Study: Department of Pathophysiology, Medical College in Wuhan University of Science and Technology (WUST), between June 2010 and July 2011. Methodology: To examine which rats have lower ability of learning and memory, thirty Wistar rats, male, 5-7 months old (360~450g), were trained and tested in step-down inhibitory avoidance task. R129d, R126d, R123d, Cdk5 (8) & CREB antibodies were respectively used to detect the content of PP1, PP2B, PP2A, Cdk5 & CREB. Densitometric analysis was used to quantitate the blots.Equal variance T test was used to analyze the escape latency and error from the two group rats, and the immunoblotting data from two groups of rat hippocampus proteins. Results: 72h after the fourth trail, MMI (mild memory impairmemt) rats showed performance markedly worse than that of the NC (normal control) rats ( latency shorter, <150sec; error more, ≥1 vs latency, 300sec; error, 0times; Both P<<0.01). From the learning and retention curves of the both groups of rats in Fig. 1, author found that in the first step-down train, the error times in MMI rats were also more than those in NC rats (P< 0.05), indicating that the ability of learning new material in MMI rats is worse than that in NC rats. The results showed that the contents of PP1 and PP-2B in MMI rats have increased or decreased ~50% (P<0.01) or ~40% (P<0.01) respectively compared with NC rats; Whereas the expression of PP2A in both groups of rats showed no obvious difference, implying that PP1 and/or PP2B might participate in the regulation of learning and memory in the rat brain. In addition, we all found that the middle degree of adverse correlation between the expression of PP1 and the latency of MMI & NC rats (-0.618, P<0.001, two tails), and the low degree of positive correlation between the expression of PP-2B and the latency of MMI & NC rats (0.381, P<0.05, two tails), indicating that the increase of PP1 content in itself might impress in part the memory ability of rats. Conclusion: It is concluded that upregulation of PP1 content may mediate worsened memory retention in rat brain.