Nogo-A aggravates oxidative damage in oligodendrocytes

Nogo-A is considered one of the most important inhibitors of myelin-associated axonal regeneration in the central nervous system.It is mainly expressed by oligodendrocytes.Although previous studies have found regulatory roles for Nogo-A in neurite outgrowth inhibition,neuronal homeostasis,precursor migration,plasticity,and neurodegeneration,its functions in the process of oxidative injury are largely uncharacterized.In this study,oligodendrocytes were extracted from the cerebral cortex of newborn Sprague-Dawley rats.We used hydrogen peroxide(H2O2)to induce an in vitro oligodendrocyte oxidative damage model and found that endogenously expressed Nogo-A is significantly upregulated in oligodendrocytes.After recombinant virus Ad-ZsGreen-rat Nogo-A infection of oligodendrocytes,Nogo-A expression was increased,and the infected oligodendrocytes were more susceptible to acute oxidative insults and exhibited a markedly elevated rate of cell death.Furthermore,knockdown of Nogo-A expression in oligodendrocytes by Ad-ZsGreen-shRNA-Nogo-A almost completely protected against oxidative stress induced by exogenous H2O2.Intervention with a Nogo-66 antibody,a LINGO1 blocker,or Y27632,an inhibitor in the Nogo-66-NgR/p75/LINGO-1-RhoA-ROCK pathway,did not affect the death of oligodendrocytes.Ad-ZsGreen-shRNA-Nogo-A also increased the levels of phosphorylated extracellular signal-regulated kinase 1/2 and inhibited BCL2 expression in oligodendrocytes.In conclusion,Nogo-A aggravated reactive oxygen species damage in oligodendrocytes,and phosphorylated extracellular signal-regulated kinase 1/2 and BCL2 might be involved in this process.This study was approved by the Ethics Committee of Peking University People’s Hospital,China(approval No.2018PHC081)on December 18,2018.

Potential Role of Akkermansia muciniphila in Parkinson's Disease and Other Neurological/Autoimmune Diseases

The composition of the gut microbiota,including Akkermatisia muciniphila(A.muciniphila),is altered in many neurological diseases and may be involved in the pathophysiological processes of Parkinson’s disease(PD).A.muciniphila,a mucin-degrading bacterium,is a potential next-generation microbe that has anti-inflammatory properties and is responsible for keeping the body healthy.As the role of A.muciniphila in PD has become increasingly apparent,we discuss the potential link between A.muciniphila and various neurological diseases(including PD)in the current review.

Clinical and muscle magnetic resonance image findings in patients with late-onset multiple acyl-CoA dehydrogenase deficiency

Background:Late-onset multiple acyl-coA dehydrogenase deficiency (MADD) is an autosomal recessive inherited metabolic disorder. It is still unclear about the muscle magnetic resonance image (MRI) pattern of the distal lower limb pre- and post-treatment in patients with late-onset MADD. This study described the clinical and genetic findings in a cohort of patients with late-onset MADD, and aimed to characterize the MRI pattern of the lower limbs.Methods:Clinical data were retrospectively collected from clinic centers of Peking University People's Hospital between February 2014 and February 2018. Muscle biopsy, blood acylcarnitines, and urine organic acids profiles, and genetic analysis were conducted to establish the diagnosis of MADD in 25 patients. Muscle MRI of the thigh and leg were performed in all patients before treatment. Eight patients received MRI re-examinations after treatment.Results:All patients presented with muscle weakness or exercise intolerance associated with variants in the electron transfer flavoprotein dehydrogenase gene. Muscle MRI showed a sign of both edema-like change and fat infiltration selectively involving in the soleus (SO) but sparing of the gastrocnemius (GA) in the leg. Similar sign of selective involvement of the biceps femoris longus (BFL) but sparing of the semitendinosus (ST) was observed in the thigh. The sensitivity and specificity of the combination of either "SO+/GA-" sign or "BFL+/ST-" sign for the diagnosis of late-onset MADD were 80.0% and 83.5%, respectively. Logistic regression model supported the findings. The edema-like change in the SO and BFL muscles were quickly recovered at 1 month after treatment, and the clinical symptom was also relieved.Conclusions:This study expands the clinical and genetic spectrums of late-onset MADD. Muscle MRI shows a distinct pattern in the lower limb of patients with late-onset MADD. The dynamic change of edema-like change in the affected muscles might be a potential biomarker of treatment response.

Novel collagen VI mutations identified in Chinese patients with Ullrich congenital muscular dystrophy

Background:We determined the clinical and molecular genetic characteristics of 8 Chinese patients with Ullrich congenital muscular dystrophy(UCMD).Methods:Clinical data of probands were collected and muscle biopsies of patients were analyzed.Exons of COL6A1,COL6A2 and COL6A3 were analyzed by direct sequencing.Mutations in COL6A1,COL6A2 and COL6A3 were identifi ed in 8 patients.Results:Among these mutations,5 were novel[three in the triple helical domain(THD)and 2 in the second C-terminal(C2)domain].We also identified five known missense or in-frame deletion mutations in THD and C domains.Immunohistochemical studies on muscle biopsies from patients showed reduced level of collagen VI at the muscle basement membrane and mis-localization of the protein in interstitial and perivascular regions.Conclusions:The novel mutations we identified underscore the importance of THD and C2 domains in the assembly and function of collagen VI,thereby providing useful information for the genetic counseling of UCMD patients.