Forebrain neurone-specific deletion of insulin-regulated aminopeptidase causes age related deficits in memory

- Inhibitors of IRAP enhance memory in rat impairment models.
- Conversely, global IRAP null mice display subtle memory deficits.
- Here, we characterise mice with targeted postnatal deletion of IRAP in neurons.
- Unexpectedly these mice exhibit defects in spatial and recognition memory.
- We propose that IRAP has novel roles in the brain development as well as memory processing.

Central infusion of Insulin-Regulated Aminopeptidase (IRAP) inhibitors improves memory in both normal rodents and in models of memory deficit. However, in contrast, the global IRAP knockout mice (KO) demonstrate age-accelerated spatial memory deficits and no improvements in performance in any memory tasks. Potentially, the observed memory deficit could be due to the absence of IRAP in the developing brain. We therefore generated a postnatal forebrain neuron-specific IRAP knockout mouse line (CamKIIalphaCre; IRAPlox/lox). Unexpectedly, we demonstrated that postnatal deletion of IRAP in the brain results in significant deficits in both spatial reference and object recognition memory at three months of age, although spatial working memory remained intact. These results indicate a significant role for IRAP in postnatal brain development and normal function of the hippocampus in adulthood.