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Human VGF-Derived Antidepressant Neuropeptide TLQP62 Promotes SH-SY5Y Neurite Outgrowth

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Abstract

TLQP62 is a neuropeptide derived from the neurotrophin-inducible VGF (non-acronymic) protein with antidepressant-like properties capable of inducing increased memory on the mouse hippocampus by promoting neurogenesis and synaptic plasticity through brain-derived neurotropic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB). Human SH-SY5Y neuroblastoma-derived cell line is widely used in neuroscience research and is known to undergo neurodifferentiation in the presence of all-trans retinoic acid by upregulating the expression of TrkB, making cells responsive to BDNF. As TLQP62 promotes BDNF expression, which in turn activates a BDNF/TrkB/CREB (cAMP response element-binding protein) pathway that upregulates VGF expression, there is a VGF-BDNF regulatory loop that seems to regulate neurogenesis. Therefore, here, we evaluate by morphological observation the ability of human TLQP62 to induce neuritogenesis of human SH-SY5Y neuroblastoma-derived cell line in a retinoic acid and BDFN-like way, making this cell line a suitable cell model for further studies concerning TLQP62 molecular mechanisms and signalling pathways.

Significance Statement

VGF has been widely explored for its role in emotional behaviour and neuropsychiatric illness (Bartolomucci et al. 2011). Although VGF levels were found reduced in leukocytes of depressed patients, after antidepressant treatment or voluntary exercise, those levels were found to be restored in the hippocampus (Hunsberger et al. 2007; Thakker-Varia et al. 2007). Administration to hippocampal cells of TLQP62 produced an increase in synaptic charge that could explain this antidepressants effects (Alder et al. 2003). This interesting role of TLQP62 in the brain, especially in the hippocampus, makes this neuropeptide an attractive target for further investigation of its role in neurogenesis, learning, memory, and neurological disorders, and possible treatment development. Thus, the identification of a receptor(s) for this peptide and associated signalling pathway(s) is of high importance, as well as a proper cell model to perform those studies.

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Acknowledgements

We acknowledge Dr. Adriana Ramos and Dr. Carmen Rodriguez-Seoane for kindly help and provide VGF-silenced SH-SY5Y cell line.

Funding

This work was supported by EC under Mare Curie Initial Training Network FP7-PEOPLE-2013-ITN (607616) and as a part of the In-Sens: Deciphering inter- and intracellular signalling in schizophrenia program. DM was the recipient of a Marie Curie Predoctoral Fellowship during this work.

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  1. CiMUS Biomedical Research Institute, IDIS, University of Santiago de Compostela, Room SS1D, Avenida de Barcelona s/n, 15782, Santiago de Compostela, Spain

    Daniela Moutinho, Sónia Veiga & Jesús R. Requena

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  1. Daniela Moutinho
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  2. Sónia Veiga
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  3. Jesús R. Requena
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DM designed the idea, conducted the experiments, analysed the results, and wrote most of the paper. SV conducted some cell culture and immunocytochemistry experiments. JR supervised throughout the work and wrote the paper with DM.

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Correspondence to Jesús R. Requena.

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Moutinho, D., Veiga, S. & Requena, J.R. Human VGF-Derived Antidepressant Neuropeptide TLQP62 Promotes SH-SY5Y Neurite Outgrowth. J Mol Neurosci 70, 1293–1302 (2020). https://doi.org/10.1007/s12031-020-01541-8

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