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VGF peptides as novel biomarkers in Parkinson’s disease

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Abstract

Parkinson’s disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra (SN). At disease onset, a diagnosis is often difficult. VGF peptides are abundant in the SN and peripheral circulation; hence, we investigate whether their plasma profile may reflect the brain dopamine reduction. Using antibodies against the VGF C-terminal portion, we analyzed the rat brain and human plasma, with immunohistochemistry and ELISA. Rats were unilaterally lesioned with 6-hyroxydopamine and sacrificed either 3 or 6 weeks later with or without levodopa treatment. Plasma samples were obtained from PD patients, either at the time of diagnosis (group 1, drug naïve, n = 23) or upon dopamine replacement (group 2, 1–6 years, n = 24; group 3, > 6 years, n = 16), compared with age-matched control subjects (group 4, n = 21). Assessment of the olfactory function was carried out in group 2 using the “Sniffin’ Sticks” test. VGF immunoreactivity was present in GABAergic neurons and, on the lesioned side, it was reduced at 3 weeks and abolished at 6 weeks after lesion. Conversely, upon levopoda, VGF labeling was restored. In PD patients, VGF levels were reduced at the time of diagnosis (1504 ± 587 vs. 643 ± 348 pmol/mL, means ± S.E.M: control vs. naïve; p < 0.05) but were comparable with the controls after long-term drug treatment (> 6 years). A linear correlation was demonstrated between VGF immunoreactivity and disease duration, levodopa equivalent dose and olfactory dysfunction. Plasma VGF levels may represent a useful biomarker, especially in the early stages of PD.

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Funding

This work was supported by the NeuroCare Onlus and Interdisciplinary Human Movement and Rehab Research Laboratory (HuMoRe) (no-profit associations). No other funding was available.

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Author notes

  1. C.C and G.C contributed equally to this paper.

Authors and Affiliations

  1. Department of Biomedical Sciences, NEF-Laboratory, University of Cagliari, 09042, Monserrato, Cagliari, Italy

    Cristina Cocco, Giulia Corda, Carlo Lisci, Barbara Noli, Manolo Carta, Carla Brancia, Elias Manca, Carla Masala & Gian-Luca Ferri

  2. Department of Neurology, “Azienda Universitario Ospedaliera” of Cagliari and University of Cagliari, Cagliari, Italy

    Francesco Marrosu & Paolo Solla

  3. Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy

    Barbara Manconi

  4. Department of Neuroscience, Neurorehabilitation Unit, University of Pisa, Pisa, Italy

    Paolo Bongioanni

Authors
  1. Cristina Cocco
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  2. Giulia Corda
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  3. Carlo Lisci
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Contributions

Cristina Cocco and Giulia Corda designed the study, provided immunohistochemistry experiments and wrote the manuscript; Carlo Lisci and Manolo Carta provided the animal model, designed the study and reviewed the manuscript; Carla Brancia and Elias Manca provided immunohistochemistry experiments; Barbara Noli provided ELISA experiments; Carla Masala provided the olfactory test and reviewed the manuscript; Francesco Marrosu, Paolo Solla, and Paolo Bongioanni provided patients, designed the study, and reviewed the manuscript; Barbara Manconi provided the spectrometry analysis and reviewed the manuscript; Gian-Luca Ferri designed the study and reviewed the manuscript.

Corresponding author

Correspondence to Cristina Cocco.

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The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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All applicable international, national and/or institutional guidelines for the care and use of animals were followed, according to the regulations set by the European Union (EEC Council 86/609; D.P.R. 116/92) and approved by the Ethical Committee of the University of Cagliari in agreement with Italian legislation. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Cocco, C., Corda, G., Lisci, C. et al. VGF peptides as novel biomarkers in Parkinson’s disease. Cell Tissue Res 379, 93–107 (2020). https://doi.org/10.1007/s00441-019-03128-1

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