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.

中文翻译：

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人类VGF衍生的抗抑郁神经肽TLQP62促进SH-SY5Y神经突增生。

摘要

TLQP62是一种神经肽，衍生自神经营养蛋白诱导型VGF（非强肽）蛋白，具有抗抑郁样特性，能够通过脑源性神经营养因子（BDNF）及其受体酪氨酸促进神经发生和突触可塑性，从而诱导小鼠海马记忆增强受体激酶B（TrkB）。人SH-SY5Y神经母细胞瘤来源的细胞系广泛用于神经科学研究，并且已知在全反式维甲酸存在下，通过上调TrkB的表达使神经分化，从而使细胞对BDNF产生反应。由于TLQP62促进BDNF表达，进而激活上调VGF表达的BDNF / TrkB / CREB（cAMP反应元件结合蛋白）途径，因此存在一个VGF-BDNF调节环，似乎在调节神经发生。所以在这里

重要性声明

VGF在情绪行为和神经精神疾病中的作用已被广泛研究（Bartolomucci等，2011）。尽管发现抑郁症患者白细胞中的VGF水平降低，但经过抗抑郁治疗或自愿运动后，海马中的VGF水平得以恢复（Hunsberger等，2007； Thakker-Varia等，2007）。向海马细胞施用TLQP62会使突触电荷增加，这可以解释这种抗抑郁药的作用（Alder等，2003）。TLQP62在大脑（尤其是在海马体）中的这种有趣作用使该神经肽成为进一步研究其在神经发生，学习，记忆和神经系统疾病以及可能的治疗方法中作用的诱人靶标。从而，