Acupuncture Alleviates Levodopa-Induced Dyskinesia via Melanin-Concentrating Hormone in Pitx3-Deficient aphakia and 6-Hydroxydopamine-Lesioned Mice.

Although L-3,4-dihydroxyphenylalanine (L-DOPA) is currently the most effective medication for treating Parkinson's disease (PD) motor symptoms, its prolonged administration causes several adverse effects, including dyskinesia. To identify the mechanisms underlying the effects of acupuncture on L-DOPA-induced dyskinesia (LID), antidyskinetic effects of acupuncture were investigated in two mouse models of PD. Acupuncture stimulation at GB34 alleviated abnormal involuntary movements (AIMs) in Pitx3-deficient aphakia mice (ak/ak) following L-DOPA administration and these effects were reproduced in 6-hydroxydopamine (6-OHDA)-lesioned mice with LID. A transcriptome analysis of the hypothalamus revealed pro-melanin-concentrating hormone (Pmch) gene was highly expressed in acupuncture-treated mouse from ak/ak model of LID as well as 6-OHDA model of LID. Acupuncture combined with the administration of MCH receptor antagonist did not have any beneficial effects on dyskinesia in L-DOPA-injected ak/ak mice, but the intranasal administration of MCH attenuated LID to the same degree as acupuncture in both ak/ak and 6-OHDA mice with LID. A gene expression profile with a hierarchical clustering analysis of the dyskinesia-induced ak/ak mouse brain revealed an association between the mechanisms underlying acupuncture and MCH. Additionally, altered striatal responses to L-DOPA injection were observed after prolonged acupuncture and MCH treatments, which suggests that these treatment modalities influenced the compensatory mechanisms of LID. In summary, present study demonstrated that acupuncture decreased LID via hypothalamic MCH using L-DOPA-administered ak/ak and 6-OHDA mouse models and that MCH administration resulted in novel antidyskinetic effects in these models. Thus, acupuncture and MCH might be valuable therapeutic candidates for PD patients suffering from LID.

Modified SJH alleviates FFAs-induced hepatic steatosis through leptin signaling pathways.

Samjunghwan (SJH) is an herbal formula used in traditional Korean medicine. This prescription has long been used in treatment of aging and lifestyle diseases. The current study showed the effect and mechanisms of anti-hepatic steatosis action of modified SJH (mSJH) in vitro and in vivo. Treatment with mSJH resulted in significantly decreased intracellular lipid accumulation in steatosis-induced cells. Furthermore, mSJH triggered the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase as well as increased the expression of leptin at both protein and gene levels. In addition, C57BL6 mice fed high-fat diet (HFD) showed significant improvements in body, liver weights and fat weights; and serum, hepatic and fecal lipid parameters in response to the treatment with mSJH. Furthermore, mSJH showed favorable effects on the hepatic expression of several genes related to lipid metabolism. Betaine, one of constituents of mSJH exerted fundamental beneficial impact on FFAs-induced cells. However, the beneficial effects of mSJH were diminished upon blocking of leptin signaling by dexamethasone, suggesting the leptin signaling as a key component in mSJH-mediated modulation of lipid homeostasis. Our results suggest that mSJH exerts an anti-hepatic steatosis effect via activation of leptin and associated signaling cascades related to lipid metabolism.

Electroconvulsive shock increases the phosphorylation of amphiphysin II in the rat cerebellum.

Amphiphysin II (Amph2) is known to undergo rapid dephosphorylation and phosphorylation at nerve terminals. After in vivo electroconvulsive shock (ECS) in the rat cerebellum, we found an electrophoretic mobility retardation of Amph2, which suggested an increased degree of phosphorylation above the non-stimulated level. This shifted signal was observed from 1 min, reached the maximum level at 5 min and extended beyond 2 h after ECS. The shifted band was markedly decreased by the phosphatase treatment. Pretreatment with cyclosporin A augmented the mobility retardation of Amph2 after ECS. Our results indicate that ECS induces the phosphorylation of Amph2 in the rat cerebellum.