title: Insulin-regulated aminopeptidase immunoreactivity is abundantly present in human hypothalamus and posterior pituitary gland, with reduced expression in paraventricular and suprachiasmatic neurons in chronic schizophrenia.
abstract: The vasopressin- and oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP) is expressed in various organs including the brain. However, knowledge about its presence in human hypothalamus is fragmentary. Functionally, for a number of reasons (genetic linkage, hydrolysis of oxytocin and vasopressin, its role as angiotensin IV receptor in learning and memory and others) IRAP might play a role in schizophrenia. We studied the regional and cellular localization of IRAP in normal human brain with special emphasis on the hypothalamus and determined numerical densities of IRAP-expressing cells in the paraventricular, supraoptic and suprachiasmatic nuclei in schizophrenia patients and controls. By using immunohistochemistry and Western blot analysis, IRAP was immunolocalized in postmortem human brains. Cell countings were performed to estimate numbers and numerical densities of IRAP immunoreactive hypothalamic neurons in schizophrenia patients and control cases. Shape, size and regional distribution of IRAP-expressing cells, as well the lack of co-localization with the glia marker glutamine synthetase, show that IRAP is expressed in neurons. IRAP immunoreactive cells were observed in the hippocampal formation, cerebral cortex, thalamus, amygdala and, abundantly, hypothalamus. Double labeling experiments (IRAP and oxytocin/neurophysin 1, IRAP with vasopressin/neurophysin 2) revealed that IRAP is present in oxytocinergic and in vasopressinergic neurons. In schizophrenia patients, the numerical density of IRAP-expressing neurons in the paraventricular and the suprachiasmatic nuclei is significantly reduced, which might be associated with the reduction in neurophysin-containing neurons in these nuclei in schizophrenia. The pathophysiological role of lowered hypothalamic IRAP expression in schizophrenia remains to be established.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany. hans-gert.bernstein@med.ovgu.de.
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Bernstein
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Susan
authors.initials: S
authors.lastname: Müller
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dobrowolny
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University Medicine, Ernst-Moritz-Arndt-University, 17475, Greifswald, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Wolke
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University Medicine, Ernst-Moritz-Arndt-University, 17475, Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Lendeckel
authors.affiliation: EUTRAF Working Group, Molecular Electrophysiology, University Hospital Magdeburg, 39120, Magdeburg, Germany.
authors.forename: Alicja
authors.initials: A
authors.lastname: Bukowska
authors.affiliation: Institute of Biochemistry and Cell Biology, Medical Faculty, University of Magdeburg, 39120, Magdeburg, Germany.
authors.forename: Gerburg
authors.initials: G
authors.lastname: Keilhoff
authors.affiliation: Institute of Pharmacology and Toxicology, Medical Faculty, University of Magdeburg, 39120, Magdeburg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Becker
authors.affiliation: Department for Legal Medicine, University of Duisburg-Essen, 45141, Essen, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Trübner
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
mesh_terms: D000368:Aged; D001344:Autopsy; D002908:Chronic Disease; D010122:Cystinyl Aminopeptidase / Q000378:metabolism*; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology*; D009481:Neurophysins / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000473:pathology; D010904:Pituitary Gland, Posterior / Q000378:metabolism*; D012559:Schizophrenia / Q000473:pathology*; D013493:Suprachiasmatic Nucleus / Q000473:pathology; D014667:Vasopressins / Q000378:metabolism
chemical_list: D009481:Neurophysins; D014667:Vasopressins; D010121:Oxytocin; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase; D005974:Glutamate-Ammonia Ligase
keywords: Human brain; Hypothalamus; Immunohistochemistry; Insulin-regulated aminopeptidase; Schizophrenia