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

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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.

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Acknowledgments

Pembroke College (University of Cambridge, Cambridge, UK) has invited JS for a Visiting Scholarship. This work was supported in part by the Stanley Medical Research Foundation to BB and JS (Grant No. 07R-1832). We are grateful to Henrik Dobrowolny for his skillful assistance in statistical analysis. Bianca Jerzykiewicz, Kathrin Paelchen, and Renate Stauch provided excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Psychiatry, University of Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Stefan Busse, Hans-Gert Bernstein, Hendrik Bielau, Ralf Brisch, Susan Müller, Tomasz Gos, Bernhard Bogerts & Johann Steiner

  2. Department of Pediatric Pulmonology and Allergology, Medical University of Hannover, Hannover, Germany

    Mandy Busse

  3. Institute of Neuropathology, University of Magdeburg, Magdeburg, Germany

    Christian Mawrin

  4. Department of Pharmacology, University of Cambridge, Cambridge, UK

    Zoltán Sarnyai

  5. Institute of Forensic Medicine, Medical University of Gdansk, Gdansk, Poland

    Tomasz Gos

  6. Pembroke College, University of Cambridge, Cambridge, UK

    Johann Steiner

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  1. Stefan Busse
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Correspondence to Johann Steiner.

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Stefan Busse and Hans-Gert Bernstein contributed equally to this work.

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Busse, S., Bernstein, HG., Busse, M. et al. Reduced density of hypothalamic VGF-immunoreactive neurons in schizophrenia: a potential link to impaired growth factor signaling and energy homeostasis. Eur Arch Psychiatry Clin Neurosci 262, 365–374 (2012). https://doi.org/10.1007/s00406-011-0282-7

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  • DOI: https://doi.org/10.1007/s00406-011-0282-7

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