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Article

The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia

1
Translational Neuroscience Research Group, Galicia Sur Health Research Institute, CIBERSAM, Hospital Álvaro Cunqueiro, Bloque Técnico, Planta 2, Sala de Investigación, Estrada Clara Campoamor, 341, 36212 Vigo, Spain
2
Translational Neuroscience Group, Universidade de Vigo, 36310 Vigo, Spain
3
Department of Psychiatry, Hospital Álvaro Cunqueiro, 36213 Vigo, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Juan F. Lopez-Gimenez
Int. J. Mol. Sci. 2021, 22(16), 8499; https://doi.org/10.3390/ijms22168499
Received: 7 June 2021 / Revised: 4 August 2021 / Accepted: 5 August 2021 / Published: 7 August 2021
(This article belongs to the Special Issue Molecular Mechanisms of Schizophrenia and Novel Targets)
The neurobiology of schizophrenia is multifactorial, comprising the dysregulation of several biochemical pathways and molecules. This research proposes a peripheral biomarker for schizophrenia that involves the second extracellular loop of norepinephrine transporter (NEText), the tropomyosin receptor kinase C (TrkC), and the neurotrophin-3 (NT-3) in T cells. The study of NEText, NT-3, and TrkC was performed in T cells and plasma extracted from peripheral blood of 54 patients with schizophrenia and 54 healthy controls. Levels of NT-3, TrkC, and NET were significantly lower in plasma and T cells of patients compared to healthy controls. Co-immunoprecipitation (co-IPs) showed protein interactions with Co-IP NEText–NT-3 and Co-IP NEText–TrkC. Computational modelling of protein–peptide docking by CABS-dock provided a medium–high accuracy model for NT-3–NEText (4.6935 Å) and TrkC–NEText (2.1365 Å). In summary, immunocomplexes reached statistical relevance in the T cells of the control group contrary to the results obtained with schizophrenia. The reduced expression of NT-3, TrkC, and NET, and the lack of molecular complexes in T cells of patients with schizophrenia may lead to a peripheral dysregulation of intracellular signaling pathways and an abnormal reuptake of norepinephrine (NE) by NET. This peripheral molecular biomarker underlying schizophrenia reinforces the role of neurotrophins, and noradrenergic and immune systems in the pathophysiology of schizophrenia. View Full-Text
Keywords: schizophrenia; neurotrophin-3; second extracellular loop of NET; tropomyosin receptor kinase C; T cells schizophrenia; neurotrophin-3; second extracellular loop of NET; tropomyosin receptor kinase C; T cells
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MDPI and ACS Style

Rodrigues-Amorim, D.; Iglesias-Martínez-Almeida, M.; Rivera-Baltanás, T.; Fernández-Palleiro, P.; Freiría-Martínez, L.; Rodríguez-Jamardo, C.; Comís-Tuche, M.; Vallejo-Curto, M.d.C.; Álvarez-Ariza, M.; López-García, M.; de las Heras, E.; García-Caballero, A.; Olivares, J.M.; Spuch, C. The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia. Int. J. Mol. Sci. 2021, 22, 8499. https://doi.org/10.3390/ijms22168499

AMA Style

Rodrigues-Amorim D, Iglesias-Martínez-Almeida M, Rivera-Baltanás T, Fernández-Palleiro P, Freiría-Martínez L, Rodríguez-Jamardo C, Comís-Tuche M, Vallejo-Curto MdC, Álvarez-Ariza M, López-García M, de las Heras E, García-Caballero A, Olivares JM, Spuch C. The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia. International Journal of Molecular Sciences. 2021; 22(16):8499. https://doi.org/10.3390/ijms22168499

Chicago/Turabian Style

Rodrigues-Amorim, Daniela, Marta Iglesias-Martínez-Almeida, Tania Rivera-Baltanás, Patricia Fernández-Palleiro, Luis Freiría-Martínez, Cynthia Rodríguez-Jamardo, María Comís-Tuche, María del Carmen Vallejo-Curto, María Álvarez-Ariza, Marta López-García, Elena de las Heras, Alejandro García-Caballero, Jose Manuel Olivares, and Carlos Spuch. 2021. "The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia" International Journal of Molecular Sciences 22, no. 16: 8499. https://doi.org/10.3390/ijms22168499

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