Vianna Monica R M, Coitinho Adriana, Izquierdo Luciana, Izquierdo Ivan
Faculty of Biosciences, National Institute of Translational Medicine.
Memory Center, Brain Institute and National Institute of Translational Neuroscience, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre RS, Brazil.
Dement Neuropsychol. 2010 Jan-Mar;4(1):23-27. doi: 10.1590/S1980-57642010DN40100004.
Protein phosphorylation mediated by serine-threonine kinases in the hippocampus is crucial to the synaptic modifications believed to underlie memory formation. The role of phosphatases has been the focus of comparatively little study.
Here we evaluate the contribution of the serine-threonine protein phosphatases 1 and 2A (PP1, PP2A) on memory consolidation.
We used immediate post-training bilateral hippocampal infusions of okadaic acid (OA, 0.01 and 10 pmol/side), a potent inhibitor of PP1 and PP2A, and measured short- [3 h] and long-term memory [24 h] (STM, LTM) of step-down inhibitory avoidance.
At the lower dose, OA inhibited both STM and LTM whereas at the higher dose it instead enhanced LTM. Pre-test infusion of these two doses of OA had no effect on retrieval.
These two doses of OA are known to selectively inhibit PP1 and PP2A respectively. These findings point to the importance of these enzymes in memory formation and also suggest a deleterious influence of endogenous hippocampal PP2A on LTM formation.
海马体中丝氨酸 - 苏氨酸激酶介导的蛋白质磷酸化对于被认为是记忆形成基础的突触修饰至关重要。磷酸酶的作用相对而言研究较少。
在此我们评估丝氨酸 - 苏氨酸蛋白磷酸酶1和2A(PP1,PP2A)对记忆巩固的作用。
我们在训练后立即双侧海马体注射冈田酸(OA,0.01和10 pmol/侧),它是PP1和PP2A的强效抑制剂,然后测量跳台抑制性回避的短期[3小时]和长期记忆[24小时](STM,LTM)。
低剂量时,OA抑制STM和LTM,而高剂量时却增强LTM。预先注射这两种剂量的OA对记忆提取没有影响。
已知这两种剂量的OA分别选择性抑制PP1和PP2A。这些发现表明这些酶在记忆形成中的重要性,也提示内源性海马体PP2A对LTM形成有有害影响。