A Survey of the Cerebral Regionalization and Ontogeny of Eight Exo- and Endopeptidases in Murines

We have established the cerebral regionalization and ontogeny of eight exo- and endopeptidases in murines. Aminopeptidases A, B, and M, post-proline dipeptidylaminopeptidase (DAP IV), and proline endopeptidase displayed a rather homogenous distribution within the brain regions with a three- to fourfold factor between the poorest and richest areas. Aminopeptidases M and B appeared maximal in the parietal cortex and nucleus accumbens, respectively, while proline endopeptidase was abundant in the piriform cortex. By contrast with the peptidases exhibiting a rather homogenous distribution, endopeptidase 24.11, angiotensin-converting enzyme, and, to a lesser extent, endopeptidase 24.15 appeared located in much more discrete cerebral zones. Angiotensin-converting enzyme activity was mainly restricted to the nigro-striatal axis. Such feature also stands for endopeptidase 24.11, which was also detected in additional zones corresponding to the globus pallidus and the nucleus accumbens. Endopeptidase 24.15 activity was maximal in the nucleus accumbens and particularly weak in the mamillary body. Neuropeptidases appeared differently regulated during development of mouse brain. Aminopeptidase M, DAP IV, and endopeptidase 24.15 were detected in utero, and their specific activities did not significantly vary until adulthood. Proline endopeptidase and endopeptidase 24.11 were detected in high quantity at day 9 before birth, then activity decreased until birth. Then, proline endopeptidase augmented and plateaued between day 3 and day 10, while endopeptidase 24.11 remained constant at a relatively low level. Finally, angiotensin-converting enzyme was virtually undetectable at early stages before parturition, then slightly increased after birth. The possibility that distinct cerebral regionalization and ontogeny of peptides could directly influence peptide physiology and/or reflect additional functions of the peptidases besides peptide degradation is discussed.