Following the establishment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model, AQP4-deficient (AQP4<sup>-/-</sup> ) mice displayed significantly stronger microglial inflammatory responses and remarkably greater losses of tyrosine hydroxylase (TH<sup>+</sup> )-positive neurons than did wild-type AQP4 (AQP4<sup>+/+</sup> ) controls.
Because activation of the innate cellular immune response, mediated by microglia, has been linked to the neurodegeneration in PD, in the present study, we evaluated the effects of lipopolysaccharide (LPS) and 6-hydroxydopamine (6-OHDA) on microglia's morphology, reflective of their activity, as well as tyrosine hydroxylase (TH)-positive neurons in SNpc and motor behavior.
Our data show that scavenging intracellular or mitochondrial ROS inhibits the microglial activation and lipid peroxidation, while protecting the tyrosine hydroxylase (TH) in the striata of PD model mice.
Moreover, immunohistochemistry for tyrosine hydroxylase (TH) revealed a significant reduction in the number of DAergic neurons in the substantia nigra of PD mice following BCCAS, particularly in the PDMCI + BCCAS group.
In the present study, we first investigated the neuroprotective effect of tDCS in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and then evaluated the effect of tDCS on the autophagy pathway. tDCS improved behavioral alterations, increased tyrosine hydroxylase protein levels and suppressed α-synuclein protein levels in MPTP-treated mice.
Tyrosine hydroxylase (TH) was increased significantly and <i>α</i>-synuclein protein expression was reduced in the EX-PD group compared to the SED-PD group.
We investigated TH polymorphism in 44 patients with sporadic PD, 48 patients with familial PD and 89 of their unaffected relatives, and 50 control subjects.
Meta-analysis results revealed statistically significant effects of acupuncture for increasing both TH levels (33.97 [95% CI 33.15-34.79]; <i>p</i> < 0.00001) and dopamine content (4.23 [95% CI 3.53-4.92]; <i>p</i> < 0.00001) compared with that observed in PD control groups.
In addition, through cultured primary mesencephalic neuron-glia cell experiments, we illustrate that Lico.A attenuates the decrease in [³H] dopamine (DA) uptake and the loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in LPS-induced PD models in vitro.
We further assessed AUR effects in vivo, investigating tyrosine hydroxylase (TH) expression in the striatum and substantia nigra of MPTP-induced PD model mice and behavioral changes after injection of AUR.
<i>In vivo</i> results demonstrated that oral administration of NTZ (50 mg/kg) in an acute MPTP mouse model of PD conferred significant protection against the loss of tyrosine hydroxylase (TH)-positive neurons of substantia nigra.
Parkinson's disease is an obvious target for the development of gene therapy procedures which could involve both the delivery of the gene encoding tyrosine hydroxylase to boost dopamine production or the delivery of genes encoding neurotrophic factors such as GDNF to promote the survival of dopaminergic neurons.
In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD, 17e significantly attenuated loss of tyrosine hydroxylase-immunopositive dopaminergic neurons, suppressed microglial activation, and alleviated PD-associated motor dysfunction.
Finally, upregulation of miR-190 inhibited the activation of microglial cells and inflammation and attenuated the tyrosine hydroxylase loss in SNpc in MPTP-induced PD mice.
This review discusses the historical overview of TH, BH4-, and other CA-related enzymes and their genes in relation to the pathophysiology of PD, the development of drugs, such as L-DOPA, and future prospects for drug and gene therapy for PD, especially the potential of induced pluripotent stem (iPS) cells.
Brain transplantation of human neural stem cells transduced with tyrosine hydroxylase and GTP cyclohydrolase 1 provides functional improvement in animal models of Parkinson disease.
Further study of the 6-OHDA-induced PD rat model indicated that FGF18 improved the behavioral dysfunction in PD rats and reduced the tyrosine hydroxylase (TH)-positive neuronal loss in the SN.
Also, immunohistochemical data using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that Tat-SAG obviously protected DA neurons in the SN against MPTP toxicity in a PD mouse model.
The prophylactic treatment of DML effectually improved the behavioral deficits, curbed the microglial-mediated neuroinflammation, and protected dopaminergic (DA) neuronal loss by restoring tyrosine hydroxylase (TH) levels in brain tissue of the MPTP-induced PD mouse model.
Characterization of intrastriatal recombinant adeno-associated virus-mediated gene transfer of human tyrosine hydroxylase and human GTP-cyclohydrolase I in a rat model of Parkinson's disease.
The significant decrease in tyrosine hydroxylase immunoreactivity in striatum supports the observed depleted level dopamine in striatum, which is relevant to the pathophysiology of PD.
Thus, (PhSe)<sub>2</sub> treatment reversed some motor impairment and TH levels in a 6-OHDA model of Parkinson's disease in rats, demonstrating a potential neurorestorative role.
Notably, the oral administration of 4b remarkably improved dyskinesia, reduced the expression of glial fibrillary acidic protein (GFAP)-a marker of neuroinflammation, and increased tyrosine hydroxylase-positive cells in 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine-induced Parkinson's disease (PD) mouse models.