title: Reduced density of hypothalamic VGF-immunoreactive neurons in schizophrenia: a potential link to impaired growth factor signaling and energy homeostasis.
abstract: Protein expression of VGF (nonacronymic) is induced by nerve/brain-derived growth factor, neurotrophin 3, and insulin. VGF is synthesized by neurons in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. After enzymatic processing, smaller VGF-derived peptides are secreted into the cerebrospinal fluid (CSF) or blood. These peptides play important roles by improving synaptic plasticity, neurogenesis, and energy homeostasis, which are impaired in schizophrenia. Based on previous observations of neuroendocrine and hypothalamic deficits in schizophrenia and to determine whether increased levels of the VGF fragment 23-62 in CSF, which have been described in a recent study, were related to changes in hypothalamic VGF expression, an immunohistochemical study was performed in 20 patients with schizophrenia and 19 matched control subjects. N- (D-20) and C-terminal (R-15) VGF antibodies yielded similar results and immunolabeled a vast majority of PVN and SON neurons. Additionally, D20-VGF immunohistochemistry revealed immunostained fibers in the pituitary stalk and neurohypophysis that ended at vessel walls, suggesting axonal transport and VGF secretion. The cell density of D20-VGF-immunoreactive neurons was reduced in the left PVN (P = 0.002) and SON (P = 0.008) of patients with schizophrenia. This study provides the first evidence for diminished hypothalamic VGF levels in schizophrenia, which might suggest increased protein secretion. Our finding was particularly significant in subjects without metabolic syndrome (patients with a body mass index ≤28.7 kg/m(2)). In conclusion, apart from beneficial effects on synaptic plasticity and neurogenesis, VGF may be linked to schizophrenia-related alterations in energy homeostasis.
authors.affiliation: Department of Psychiatry, University of Magdeburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Busse
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Bernstein
authors.forename: Mandy
authors.initials: M
authors.lastname: Busse
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bielau
authors.forename: Ralf
authors.initials: R
authors.lastname: Brisch
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Susan
authors.initials: S
authors.lastname: Müller
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Sarnyai
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gos
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002452:Cell Count; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism / Q000473:pathology; D011180:Postmortem Changes; D012559:Schizophrenia / Q000473:pathology*
chemical_list: D009479:Neuropeptides; C522413:VGF peptide