CHANGES IN PUROMYCIN-SENSITIVE AMINOPEPTIDASES IN POSTMORTEM SCHIZOPHRENIC BRAIN-REGIONS

We studied the distribution of puromycin-sensitive aminopeptidase (PSA ) in well-defined human brain areas by Western immunoblot in an attemp t to examine its possible role in schizophrenia. The schizophrenic bra ins were from suicide victims (n = 13) of either sex, with an age rang e of 30-60 yr (average 45). The controls were mostly victims of myocar dial infarction (n = 12), of either sex and between 32 and 56 yr old ( average 44). The brain regions were obtained within 48 h after death. After ultracentrifugation the PSA was quantified by Western blot analy sis using a PSA antiserum. The distribution of the two most abundant a ntigens, MW 100 kDa (PSA-100) and 170 kDA (PSA-170), were compared. PS A-100 had peptidase activity, PSA-170 did not. PSA-100 was found in al l of the regions studied. In the control brain areas prefrontal cingul ate and frontal cortices, thalamus, hippocampus, hypothalamus and oute r globus pallidus contained significantly more PSA-100 than the corres ponding areas from schizophrenic brain. PSA-170 was mostly found only in areas of schizophrenic brains. In three control brains, in one area of each, it could be detected, but the level in each of these regions was less than 30% of that in the corresponding schizophrenic area. PS A-170 was found in all the schizophrenic brains, in 20 of the 35 regio ns we studied, with parahippocampal cortex the highest (134 ng/g wet t issue) and frontal inferior cortex the lowest (9.3 ng/g wet tissue). I t was not detectable in cerebral or cerebellar white matter. Our data show that the amounts and distribution of PSA-100 and PSA-170 in the s chizophrenic brain are distinctively different from those of the contr ols and PSA-170, a protein of unknown function, is restricted mostly t o schizophrenic brain areas. The difference is not due either to neuro leptic treatment of the patient or to postmortem proteolysis of the br ain samples.