Overlapping regional distribution of CCK and TPPII mRNAs in Cynomolgus monkey brain and correlated levels in human cerebral cortex (BA 10).
Tripeptidyl peptidase II (TPPII) is a high molecular weight exopeptidase important in inactivating extracellular cholecystokinin (CCK). Our aims were to study the anatomical localization of TPPII and CCK mRNA in the Cynomolgus monkey brain as a basis for a possible functional anatomical connection between enzyme (TPPII) and substrate (CCK) and examine if indications of changes in substrate availability in the human brain might be reflected in changes of levels of TPPII mRNA.


METHODS
mRNA in situ hybridization on postmortem brain from patients having had a schizophrenia diagnosis as compared to controls and on monkey and rat brain slices.


RESULTS
overlapping distribution patterns of mRNAs for TPPII and CCK in rat and monkey. High amounts of TPPII mRNA are seen in the neocortex, especially in the frontal region and the hippocampus. TPPII mRNA is also present in the basal ganglia and cerebellum where CCK immunoreactivity and/or CCK B receptors have been found in earlier studies, suggesting presence of CCK-ergic afferents from other brain regions. Levels of mRNAs for CCK and TPPII show a positive correlation in postmortem human cerebral cortex Brodmann area (BA) 10. TPPII mRNA might be affected following schizophrenia.


CONCLUSIONS
overall TPPII and CCK mRNA show a similar distribution in rat and monkey brain, confirming and extending earlier studies in rodents. In addition, correlated levels of TPPII and CCK mRNA in human BA 10 corroborate a functional link between CCK and TPPII in the human brain.
Radu
Diana
D
Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden. diana.radu@ki.se
Tomkinson
Birgitta
B
Zachrisson
Olof
O
Weber
Günther
G
de Belleroche
Jacqueline
J
Hirsch
Steven
S
Lindefors
Nils
N
D000626:Aminopeptidases; D000818:Animals; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000378:metabolism*; D002766:Cholecystokinin / Q000235:genetics* / Q000378:metabolism; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008252:Macaca fascicularis; D008297:Male; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D018709:Statistics, Nonparametric
D012333:RNA, Messenger; D002766:Cholecystokinin; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases