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

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.