Strain differences in the effects of Angiotensin IV on mouse cognition

Angiotensin IV has been shown to improve learning and memory in rodents. Strain dependent variation in murine behaviour, aminopeptidase activity and inhibitory effect of Angiotensin IV, structural variation in insulin regulated aminopeptidase (IRAP) and aminopeptidase N (ApN) and expression of the encoding genes were explored. Strain differences in the behavioural response to Angiotensin IV were observed, where CD mice were refractory. All strains showed inhibition of aminopeptidase activity by Angiotensin IV but CD mice displayed reduced endogenous aminopeptidase activity. No differences in the coding sequence of IRAP or ApN were found. RT-PCR analysis showed no difference in IRAP expression between strains but an increased expression of ApN was observed in CD mice. The lack of cognitive response of CD mice to Angiotensin IV cannot be explained through variation within IRAP sequence nor expression but the results highlight a potential role for ApN in the effects of Angiotensin IV.