Acupuncture Inhibits the Increase in Alpha-Synuclein in Substantia Nigra in an MPTP- Induced Parkinsonism Mouse Model.

Parkinson's disease, a progressive neurodegenerative disease, is caused by the loss of dopaminergic neurons in the substantia nigra (SN). It is characterized by the formation of intracytoplasmic Lewy bodies that are primarily composed of the protein alpha-synuclein (α-syn), along with dystrophic neurites. Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in Parkinsonism animal models. We investigated the role of acupuncture in inhibiting the increase in α-syn expression that is related to dopaminergic cell loss in the SN in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonism mouse model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in the SN. Moreover, acupuncture stimulation attenuated the increase in α-syn in SN. Acupuncture stimulation also maintained the phosphorylated α-syn on serine 129 at levels similar to the control group. Our findings indicate that the MPTP-mediated increase in α-syn, and the acupuncture-mediated inhibition of the increase in α-syn, may be responsible for the neuroprotective effects of acupuncture in the SN following damage induced by MPTP.

Mechanism of the neuroprotective effect of injecting brain cells on ST36 in an animal model of Parkinson's disease.

In Parkinson's disease, the dopaminergic neurons of the brain are destroyed. Dopamine is an important neurotransmitter that acts on the basal ganglia of the brain, allowing precise body movement. In the early stages of Parkinson's disease, levodopa appears to alleviate clinical symptoms; however, during long-term use, motor complications occur. There is no clear treatment or remedy for Parkinson's disease; therefore, the development of novel therapies is urgently required. In the present study, mouse choroid plexus cells were transplanted into ST36 in a mouse model of Parkinson's disease to determine whether the motor function could be restored. Pole tests showed changes in motor dysfunction in the mice. The athletic ability of the mice was significantly lowered after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection and significantly increased after choroidal neuron cell treatment. Injection of di-alkyl indocarbocyanine (DiI) (as a trace substance) confirmed that the choroid plexus cells injected into acupuncture point ST36 were transferred to the brain. In the Parkinson's disease model, choroid plexus cell injection into ST36 inhibited the decrease in tyrosine hydroxylase (TH) expression and decreased the activation of inflammatory factors mitochondrial cytochrome C oxidase (COX2) and inducible NO synthase (iNOS). Apoptosis factors Cytochrome C and BCL2 associated X, apoptosis regulator (BAX) levels were decreased and B-Cell CLL/Lymphoma 2 (BCL2) levels were increased. Taken together, these results suggest that the injection of choroid plexus cell at ST36 had neuroprotective effects in the Parkinson's disease mouse model. The results suggest new possibilities for the treatment of Parkinson's disease.

Decreased expression of serum- and glucocorticoid-inducible kinase 1 (SGK1) promotes alpha-synuclein increase related with down-regulation of dopaminergic cell in the Substantia Nigra of chronic MPTP-induced Parkinsonism mice and in SH-SY5Y cells.

Parkinson's disease (PD) is a chronically progressive neurodegenerative disease, with its main pathological hallmarks being a dramatic loss of dopaminergic neurons predominantly in the Substantia Nigra (SN), and the formations of intracytoplasmic Lewy bodies and dystrophic neurites. Alpha-synuclein (α-syn), widely recognized as the most prominent element of the Lewy body, is one of the representative hallmarks in PD. However, the mechanisms behind the increased α-syn expression and aggregation have not yet been clarified. To examine what causes α-syn expression to increase, we analyzed the pattern of gene expression in the SN of mice intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), where down-regulation of dopaminergic cells occurred. We identified serum- and glucocorticoid-dependent kinase 1 (SGK1) as one of the genes that is evidently downregulated in chronic MPTP-intoxication. The results of Western blot analyses showed that, together with the down-regulation of dopaminergic cells, the decrease in SGK1 expression increased α-syn expression in the SN in a chronic MPTP-induced Parkinsonism mouse. For an examination of the expression correlation between SGK1 and α-syn, SH-5YSY cells were knocked down with SGK1 siRNA then, the downregulation of dopaminergic cells and the increase in the expression of α-syn were observed. These results suggest that decreased expression of SGK1 may play a critical role in increasing the expression of α-syn, which is related with dopaminergic cell death in the SN of chronic MPTP-induced Parkinsonism mice and in SH-SY5Y cells.