Effects of beta-amyloid and apolipoprotein E4 on hippocampal choline acetyl transferase in rats / 中华病理学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of beta-amyloid (Aβ) and apolipoprotein E4(apoE4) on choline acetyl transferase (ChAT) in hippocampus and to explore possible the synergistic effect of both Aβ and apoE4.</p><p><b>METHODS</b>Male Wistar rats were divided into four groups: control group, Aβ group, apoE4 group and Aβ + apoE4 group. Rats in different group received injection of normal saline, Aβ1-40, apoE4 and Aβ1-40 + apoE4, respectively, into bilateral hippocampus CA1 regions under the control of a brain stereotaxic apparatus. The learning-memory ability with the escape latency and the times of passing platform and the expression of ChAT in hippocampus CA1 regions were documented.</p><p><b>RESULTS</b>The escape latency at fifth day and the times of passing platform and ChAT mRNA PU values were obtained for the control group (10.75 s ± 2.44 s, 4.13 ± 0.64, and 28.90 ± 4.43), apoE4 group (23.88 s ± 4.32 s, 2.38 ± 0.52, and 20.85 ± 3.98), Aβ group (43.50 s ± 9.78 s, 1.38 ± 0.52, and 16.96 ± 2.53), and Aβ + apoE4 group (70.63 s ± 10.04 s, 0.75 ± 0.71, and 13.01 ± 2.21). Through 5 days of training all animals acquired learning-memory ability with the gradually shortened escape latency, although injection of Aβ1-40 and apoE4 all induced learning-memory damage, due to a significantly prolonged the escape latency at fifth day (P < 0.01) and markedly decreased the times of passing platform (P < 0.01) in both Aβ and apoE4 group than in control group. An interaction between Aβ and apoE4 also was observed, with further prolonged escape latency(P < 0.01). ChAT mRNA PU values were significantly lower in the Aβ group and apoE4 group than in the control group (P < 0.01). Aβ and apoE4 demonstrated interaction in lowering ChAT mRNA level(P < 0.05).</p><p><b>CONCLUSIONS</b>Both Aβ and apoE4 induce an injury to hippocampal cholinergic system and its learning-memory ability, in which Aβ and apoE4 have a synergistic effect in the initiation of such injury.</p>