Targeting gut-brain axis through scalp-abdominal electroacupuncture in Parkinson's disease.

BACKGROUND: Evidence suggests that the pathogenesis of Parkinson's disease (PD) is initiated in the gut rather than in the brain. Thus, targeting the gut in early stages may have the potential to halt disease progression and alleviate symptoms. Various acupuncture techniques have been used to treat patients with PD and have shown promising results. However, previous acupuncture techniques focused on the brain and motor symptoms. We aimed to determine if targeting PD patients' gut-brain axis through electroacupuncture could be an effective, safe, and low-cost therapeutic option for management of non-motor and motor symptoms. METHODS: Thirty patients with mild to moderate PD were randomised into an intervention (n = 15) and a control group (n = 15). The intervention group received electroacupuncture twice a week for 30 min based on conventional drug treatment for 8 weeks. Conventional drug treatment was continued in the control group. The primary outcomes were changes in the score of clinical scales including the Non-motor Symptom Rating Scale (NMSS), PD Sleep Scale (PDSS), Bristol Stool Function Scale (BSFS), and Patient Associated Constipation and Quality of Life Scale (PAC-QOL). The secondary outcomes were the Unified PD Rating Scale (UPDRS) and Modified Hoehn-Yahr Staging Scale scores. Stool samples from the intervention group were collected before and after the procedure and were sent for gene sequencing. Adverse effects and personal impressions of the patients were noted during the course of the trial. RESULT: An 8-week course of scalp-abdominal electroacupuncture treatment was effective in improving the NMSS, PDSS, and UPDRS scores in patients with PD. Further, there was statistical significance in the two subdomains of NMSS, namely sleep/fatigue and miscellaneous, further implying the efficacy of acupuncture on sleep disturbance. However, although the current acupuncture treatment was gut targeted, it had no effect on BSFS or PAC-QOL. Apart from improved UPDRS motor scores and activities of daily living scores, acupuncture had no significant impact on scores of mentation, behaviour, mood, and therapy complications. Acupuncture did not alter the Hoehn and Yahr stage. Significant alterations in gut bacterial composition were detected in nine taxa at the genus level. The relative abundances of the genera Bacteroides and Parasutterella were significantly increased after the intervention, whereas the abundances of the genera Dialister, Hungatella, Barnesiella, Megasphaera, Allisonella, Intestinimon, and Moryella were significantly lower. CONCLUSION: An 8-week scalp-abdominal electroacupuncture treatment may be a complementary and alternative vehicle for PD patients. We detected nine taxa at the genus level which were significantly altered after treatment, emphasising the role of the gut-brain axis in the process.

Moderate- and Low-Dose of Atorvastatin Alleviate Cognition Impairment Induced by High-Fat Diet via Sirt1 Activation.

Mounting evidences have demonstrated that diet-induced obesity is associated with cognition impairment via increasing oxidative stress and inflammation in the brain. Atorvastatin (Ator, a HMG-CoA reductase inhibitor) is a cholesterol lowering drug. Studies have reported that Ator can ameliorate the development and progression of cognition impairment. Additionally, silent information regulator 1 (SIRT1) has been demonstrated to be beneficial in cognition impairment. However, the interaction between Ator and SIRT1 activation for cognition impairment remains unclear. This study aimed to identify a relationship between the use of Ator and cognition impairment induced by high-fat diet via Sirt1 activation. A total of 60 healthy male C57BL/6J mice were purchased and then divided into 6 groups, including normal diet group (control), a high-fat diet group (40%HFD, 40% energy from fat), a model group (60%HFD, 60% energy from fat), and model group treated with different doses of Ator (high-dose (80 mg), moderate-dose (40 mg), and low-dose (20 mg) groups). All interventions took place for 7 months. Metabolic phenotypes were characterized for body weight and analysis of serum lipid level. The level of cognition development was examined by Morris water maze (MWM) approach and novel object recognition test (NORT); besides, the expression of Creb1, Gap-43, BDNF, CaMKII, and ERKs of frontal cortex and hippocampus was determined by reverse transcription polymerase chain reaction (RT-PCR). Then, the levels of factors related to inflammation (TNF-a, IL-1ß, HMGB1 and IL-6) and oxidation stress (SOD, MDA, CAT and GSH-Px) were assessed using commercially available kits. Finally, SIRT1 and its downstream molecules (Ac-FoxO1, Ac-p53, Ac-NF-κB, Bcl-2 and Bax) were evaluated by Western blot analysis. Compared with the 60% HFD group, body weight and serum lipid levels were significantly decreased in the Ator treated groups. The results of MWM and NORT, as well as the levels of Creb1, Gap-43, BDNF, CaMKII, and ERKs were markedly reversed in the moderate- and low-dose of Ator treated groups. Meanwhile, the expression of IL-1ß, TNF-a, IL-6, HMGB1, and MDA was notably decreased, whereas the activity of SOD, CAT, and GSH-Px was increased. It was also revealed that the expression of SIRT1 was remarkably unregulated, the level of Bcl-2 was upregulated, and the content of Ac-FoxO1, Ac-p53, Ac-NF-κB, and Bax was downregulated in the moderate- and low-dose of Ator. Furthermore, results showed that the effect of moderate-dose of Ator was significantly greater than the low-dose of Ator. However, these effects were not observed in the high-dose of Ator. Our results showed that moderate- and low-dose of Ator can significantly attenuate cognition impairment induced by HFD through its antioxidant and anti-inflammatory functions related to SIRT1 activation.