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Abstract
Tryptophan hydroxylase type 2 (Tph2) is the rate-limiting enzyme for serotonin (5-HT) biosynthesis in the brain. Dysfunctional Tph2 alters 5-HT biosynthesis, leading to a deficiency of 5-HT, which could have repercussions on human behavior. In the last decade, several studies have associated polymorphisms of the TPH2 gene with suicidal behavior. Additionally, a 5-HT deficiency has been implicated in various psychiatric pathologies, including alcoholism, impulsive behavior, anxiety, and depression. Therefore, the TPH2 gene could be an ideal target for analyzing the effects of a 5-HT deficiency on brain function. The aim of this study was to use the construct pIRES-hrGFP-1a-Tph2-FLAG to treat CD1-male mice and to transfect HEK-293-cells and then to evaluate whether this treatment increases 5-HT production. 5-HT levels were enhanced 48 h post-transfection, in HEK-293 cells. Three days after the ocular administration of pIRES-hrGFP-1a-Tph2-FLAG to mice, putative 5-HT production was significantly higher than in the control in both hypothalamus and amygdala, but not in the brainstem. Further research will be needed on the possible application of this treatment for psychiatric diseases involving a Tph2 dysfunction or serotonin deficiency.
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1 Centro Médico Nacional “La Raza”, IMSS, Unidad de Investigación Biomédica en Inmunología e Infectología, Hospital de Infectología, Ciudad de México, México (GRID:grid.418382.4) (ISNI:0000 0004 1759 7317)
2 Centro Médico Nacional “Siglo XXI”, IMSS, Unidad de Investigación Médica en Enfermedades Endócrinas, UMAE, Hospital de Especialidades, Ciudad de México, México (GRID:grid.418385.3)
3 Centro Médico Nacional “Siglo XXI”, IMSS, Unidad de Investigación Médica en Enfermedades Neurólogicas, UMAE, Hospital de Especialidades, Ciudad de México, México (GRID:grid.418385.3)
4 Universidad Nacional Autónoma de México, División de Neurociencias, Instituto de Fisiología Celular, Ciudad de México, México (GRID:grid.9486.3) (ISNI:0000 0001 2159 0001)
5 Instituto Nacional de Cardiología Ignacio Chávez., Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, UNAM, Ciudad de México, México (GRID:grid.419172.8) (ISNI:0000 0001 2292 8289)
6 Sección de Estudios de Posgrado e Investigación de la Escuela Superior de Medicina del Instituto Politécnico Nacional, Ciudad de México, México (GRID:grid.418275.d) (ISNI:0000 0001 2165 8782)