Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway.

Increasing evidence has shown that gut dysbacteriosis may play a crucial role in neuroinflammation in Parkinson's disease (PD). However, the specific mechanisms that link gut microbiota to PD remain unexplored. Given the critical roles of blood-brain barrier (BBB) dysfunction and mitochondrial dysfunction in the development of PD, we aimed to evaluate the interactions among the gut microbiota, BBB, and mitochondrial resistance to oxidation and inflammation in PD. We investigated the effects of fecal microbiota transplantation (FMT) on the physiopathology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The aim was to explore the role of fecal microbiota from PD patients and healthy human controls in neuroinflammation, BBB components, and mitochondrial antioxidative capacity via the AMPK/SOD2 pathway. Compared to control mice, MPTP-treated mice exhibited elevated levels of Desulfovibrio, whereas mice given FMT from PD patients exhibited enriched levels of Akkermansia and mice given FMT from healthy humans showed no significant alterations in gut microbiota. Strikingly, FMT from PD patients to MPTP-treated mice significantly aggravated motor impairments, dopaminergic neurodegeneration, nigrostriatal glial activation and colonic inflammation, and inhibited the AMPK/SOD2 signaling pathway. However, FMT from healthy human controls greatly improved the aforementioned MPTP-caused effects. Surprisingly, the MPTP-treated mice displayed a significant loss in nigrostriatal pericytes, which was restored by FMT from healthy human controls. Our findings demonstrate that FMT from healthy human controls can correct gut dysbacteriosis and ameliorate neurodegeneration in the MPTP-induced PD mouse model by suppressing microgliosis and astrogliosis, ameliorating mitochondrial impairments via the AMPK/SOD2 pathway, and restoring the loss of nigrostriatal pericytes and BBB integrity. These findings raise the possibility that the alteration in the human gut microbiota may be a risk factor for PD and provide evidence for potential application of FMT in PD preclinical treatment.

Combined measurement of plasma cystatin C and low-density lipoprotein cholesterol: A valuable tool for evaluating progressive supranuclear palsy.

INTRODUCTION: Progressive supranuclear palsy (PSP) was previously thought as a cause of atypical Parkinsonism. Although Cystatin C (Cys C) and low-density cholesterol lipoprotein-C (LDL-C) are known to play critical roles in Parkinsonism, it is unknown whether they can be used as markers to distinguish PSP patients from healthy subjects and to determine disease severity. METHODS: We conducted a cross-sectional study to determine plasma Cys C/HDL/LDL-C levels of 40 patients with PSP and 40 healthy age-matched controls. An extended battery of motor and neuropsychological tests, including the PSP-Rating Scale (PSPRS), the Non-Motor Symptoms Scale (NMSS), Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE), was used to evaluate the disease severity. Receiver operating characteristic (ROC) curves were adopted to assess the prognostic accuracy of Cys C/LDL-C levels in distinguishing PSP from healthy subjects. RESULTS: Patients with PSP exhibited significantly higher plasma levels of Cys C and lower LDL-C. The levels of plasma Cys C were positively and inversely correlated with the PSPRS/NMSS and MMSE scores, respectively. The LDL-C/HDL-C ratio was positively associated with PSPRS/NMSS and GDS scores. The ROC curve for the combination of Cys C and LDL-C yielded a better accuracy for distinguishing PSP from healthy subjects than the separate curves for each parameter. CONCLUSIONS: Plasma Cys C and LDL-C may be valuable screening tools for differentiating PSP from healthy subjects; while they could be useful for the PSP intensifies and severity evaluation. A better understanding of Cys C and LDL-C may yield insights into the pathogenesis of PSP.

Mechanical stretch regulates microRNA expression profile via NF-κB activation in C2C12 myoblasts.

MicroRNAs (miRNAs/miRs) and nuclear factor (NF)-κB activation are involved in mechanical stretch-induced skeletal muscle regeneration. However, there are a small number of miRNAs that have been reported to be associated with NF­κB activation during mechanical stretch-induced myogenesis. In the present study, C2C12 myoblasts underwent cyclic mechanical stretch in vitro, to explore the relationship between miRNA expression and NF­κB activation during stretch-mediated myoblast proliferation. The results revealed that 10% deformation, 0.125 Hz cyclic mechanical stretch could promote myoblast proliferation. The miRNA expression profile was subsequently altered; miR­500, ­1934, ­31, ­378, ­331 and ­5097 were downregulated, whereas miR­1941 was upregulated. These miRNAs were all involved in stretch­mediated myoblast proliferation. Notably, the expression of these miRNAs was reversed following treatment of 0.125 Hz mechanically stretched C2C12 cells with NF­κB inhibitors, which was accompanied by C2C12 cell growth suppression. Therefore, the present study is the first, to the best of our knowledge, to demonstrate that the NF­κB­dependent miRNA profile is associated with mechanical stretch-induced myoblast proliferation.

[Critical illness polyneuropathy in a patient with Parkinson disease: a case report and review of the literature].

OBJECTIVE: To report a case of critical illness polyneuropathy (CIP) with Parkinson disease and discuss the development, clinical features and early diagnosis of this condition. METHODS: The clinical data of a patient with CIP and Parkinson's disease and the relevant literature were reviewed. RESULTS: This case showed no typical disease course of sepsis, and the condition exacerbated rapidly. The patient presented initially with abnormal homeostasis, followed by rapid onset of respiratory muscle weakness to require mechanical ventilation, but no limb weaknesses were detected. Intravenous antibiotics and aggressive treatment of sepsis did not produce any positive responses to wean from mechanical ventilation. Examinations of creatine kinase and cerebrospinal fluid showed no abnormalities. Electromyography and nerve conduction studies demonstrated declined nerve conduction velocity and decreased sensory and motor muscle action potentials, suggesting the possibility of CIP. CONCLUSION: In patients with Parkinson disease, the occurrence of sepsis with prolonged mechanical ventilation and limb weakness indicates the necessity of neurophysiological examination, muscle biopsies and laboratory tests, which may help detect CIP in the early phase. Proper interventions of sepsis may reduce the likeliness of CIP. Elimination of the risk factors and aggressive management of sepsis can be effective measures for preventing CIP.