The role of Insulin-Like Growth Factors in long-term memory enhancement.

摘要

Both short-term and long-term memories allow organisms to adapt their actions to changing environments. However, over time, memories may become less strong and be eventually forgotten. Furthermore, the loss of long-term memory that accompanies a number of diseases can be devastating. Clinically, there is an urgent need to find interventions that enhance and preserve memory function in both a healthy and disease state.;In this thesis, I have studied the role of a system of growth factors known as the Insulin-Like Growth Factor (IGF) system in long-term memory enhancement.;First, I have studied the effects of the IGFs on both hippocampal and amygdala dependent tasks. I have found that IGF-II enhances memories of hippocampus, but not amygdala, dependent tasks significantly and persistently, and that Insulin also enhances those same forms of memory, but transiently. In contrast, I found that IGF-I does not enhance either type of memory.;Secondly, I have elucidated the role of IGF-II in the enhancement of remote memories. I found that IGF-II, but not IGF-I or Insulin, enhances 2-week old IA memories when injected into the rat anterior cingulate cortex (aCC) immediately after or 2 weeks after training, but does not enhance recent long-term memory (up to 9d after training) when injected immediately or 48h after training. When IGF-II is injected immediately after a reactivation, the period of enhancement can be extended to 4 weeks, but not 2 months, after training.;Lastly, I characterized the types of memories enhanced by systemic treatment of IGF-II in both young adult C57Bl/6J (B6) mice and in a mouse model of autism spectrum disorder (ASD), BTBR T+ Itpr3tf/J (BTBR), In B6 mice, I showed that systemically injected IGF-II enhances both aversive and non-aversive memories, as well as working, short-term and long-term memories, yet produces no adverse effects in mice and does not restrict memory flexibility. In BTBR mice, which exhibit profound behavioral phenotypes characteristic of ASD, I found that IGF-II reverses social recognition deficits, repetitive behaviors and memory deficits.;Together, my studies indicate that IGF-II is a powerful enhancer of long-term hippocampus dependent memories that is potentially useful for clinical therapeutics.