Prolyl oligopeptidase activity (POP) in early stage and medicated schizophrenia and in an animal model for schizophrenia study: in vivo effects of psychopharmacological substances on enzyme activity

Prolyl oligopeptidase (POP) is an enzyme highly expressed in the central nervous system, playing important roles in neurodevelopment, memory and learning. Moreover, changes in POP activity in peripheral blood have been associated with various neuropsychiatric disorders. Herein, the POP activity was measured by monitoring the hydrolysis of a specific MCA peptide substrate in plasma or homogenate of selected brain regions from a validated animal model for schizophrenia (SCZ) studies, namely spontaneously hypertensive rats (SHR), compared with control normotensive Wistar rats (NWR), before and after the treatment with antipsychotics. We also evaluated POP activity in plasma from patients with early stage or with chronic schizophrenia (SCZ) relative to paired healthy controls (HCs). No significant differences in POP activity were observed for patients in early stage or with chronic SCZ compared to HCs. POP activity was significantly lower in the plasma of SHR compared to NWR, with no changes in activity observed after a chronic treatment with typical or atypical antipsychotics. Interestingly, a significant decrease in POP activity was observed solely in prefrontal cortex of the SCZ animal model but not in any other brain region or plasma of NWR or SHR after the chronic treatment with antipsychotics. Despite the well-known cognitive impairments improvement in vivo demonstrated for the POP inhibitors, our data suggest the lack of correlation between the activity of this enzyme and early stage or chronic SCZ, as well as no significative pharmacological responses to psychoactive compounds were noticed for this enzyme here.