Reduced density of hypothalamic VGF-immunoreactive neurons in schizophrenia: a potential link to impaired growth factor signaling and energy homeostasis

  • Stefan Busse
  • Hans-Gert Bernstein
  • Mandy Busse
  • Hendrik Bielau
  • Ralf Brisch
  • Christian Mawrin
  • Susan Müller
  • Zoltán Sarnyai
  • Tomasz Gos
  • Bernhard Bogerts
  • Johann Steiner
Original Paper

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/m2). In conclusion, apart from beneficial effects on synaptic plasticity and neurogenesis, VGF may be linked to schizophrenia-related alterations in energy homeostasis.

Keywords

Schizophrenia Hypothalamus Postmortem Histopathology VGF Granins 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Stefan Busse
    • 1
  • Hans-Gert Bernstein
    • 1
  • Mandy Busse
    • 2
  • Hendrik Bielau
    • 1
  • Ralf Brisch
    • 1
  • Christian Mawrin
    • 3
  • Susan Müller
    • 1
  • Zoltán Sarnyai
    • 4
  • Tomasz Gos
    • 1
    • 5
  • Bernhard Bogerts
    • 1
  • Johann Steiner
    • 1
    • 6
  1. 1.Department of PsychiatryUniversity of MagdeburgMagdeburgGermany
  2. 2.Department of Pediatric Pulmonology and AllergologyMedical University of HannoverHannoverGermany
  3. 3.Institute of NeuropathologyUniversity of MagdeburgMagdeburgGermany
  4. 4.Department of PharmacologyUniversity of CambridgeCambridgeUK
  5. 5.Institute of Forensic MedicineMedical University of GdanskGdanskPoland
  6. 6.Pembroke College, University of CambridgeCambridgeUK

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