Evidence Details for Tph2
PMID Title Journal Year Abstract
25983633 Neuroprotective changes in degeneration-related gene expression in the substantia nigra following acupuncture in an MPTP mouse model of Parkinsonism: Microarray analysis. Genet Mol Biol. 2015 Mar;38(1):115-27. doi: 10.1590/S1415-475738120140137. Epub 2014 Mar 17. 2015 Mar Parkinson's disease (PD) is a neurodegenerative disorder characterized by the death of dopamine-generating cells in the substantia nigra (SN). Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in Parkinsonism animal models. The present study investigated changes in gene expression profiles measured using whole transcript array in the SN region related to the inhibitory effects of acupuncture in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonism model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in the SN region; stimulation at non-acupoints did not suppress this decrease. Gene array analysis revealed that 22 (10 annotated genes: Cdh1, Itih2, Mpzl2, Rdh9, Serping1, Slc6a13, Slc6a20a, Slc6a4, Tph2, and Ucma) probes that were up-regulated in MPTP animals relative to controls were exclusively down-regulated by acupuncture stimulation. In addition, 17 (two annotated genes: 4921530L21Rik and Gm13931) probes that were down-regulated in MPTP animals compared to controls were exclusively up-regulated by acupuncture stimulation. These findings indicate that the 39 probes (12 annotated genes) affected by MPTP and acupuncture may be responsible for the inhibitory effects of acupuncture on degeneration-related gene expression in the SN following damage induced by MPTP intoxication."

Evidence Sentence: Gene array analysis revealed that 22 (10 annotated genes: Cdh1, Itih2, Mpzl2, Rdh9, Serping1, Slc6a13, Slc6a20a, Slc6a4, Tph2, and Ucma) probes that were up-regulated in MPTP animals relative to controls were exclusively down-regulated by acupuncture stimulation.
Evidence Sentence: Tryptophan hydroxylase 2 (Tph2), with a molecular weight of 56 kDa, is the predominant form of this enzyme present in brain extracts from the mesencephalic tegmentum, striatum, and hippocampus.
Evidence Sentence: Tph2 initiates serotonin synthesis in mammals with Tph1, and plays a critical role in the maintenance of brain serotonin homeostasis.
Evidence Sentence: Tph2-derived serotonin is involved in the regulation of behavior and autonomic pathways but is not essential for adult life .
Evidence Sentence: However, Tph2 is known to be highly labile to oxidation.
Evidence Sentence: Therefore, the oxidative processes that prevail in PD may cause a misfolding of Tph2 and result in the modification of serotonin function such as is seen in dopamine neurons.
Evidence Sentence: Tph2 oxidation inhibits its activity and leads to the formation of high-molecular-weight aggregates in a dithiothreitol-reversible manner.
Evidence Sentence: Alteration of serotonin levels by Tph2 hyperinnervation affects the wiring of the brain and can produce long-lasting changes leading to the development of neurodevelopmental disorders such as PD.
Evidence Sentence: Tph2 was involved in tryptophan metabolism and serotonergic synapse at significant levels.
Evidence Sentence: These findings demonstrate that both MPTP and acupuncture at acupoints influence Cdh1, Tph2, Slc6a4, Serping1, Slc6a13, and Gm13931 expression in the indicated pathways in the SN region.
Evidence Sentence: Expression levels of Rdh9, Slc6a4, Tph2 and Ucma, which were up-down regulated in the microarray analysis, also showed up-down regulation in real time RT-PCR (Figure 3).
Evidence Sentence: The microarray results indicate that Slc6a4 and Tph2, which are involved in PD, and Mpzl2 and Serping1, which are involved in inflammation, are primary causes of neurodegenerative disorders, and their expression can be maintained at similar to normal levels by acupuncture.