Axonal autophagic vesicle transport in the rat optic nerve in vivo under normal conditions and during acute axonal degeneration.

Neurons pose a particular challenge to degradative processes like autophagy due to their long and thin processes. Autophagic vesicles (AVs) are formed at the tip of the axon and transported back to the soma. This transport is essential since the final degradation of the vesicular content occurs only close to or in the soma. Here, we established an in vivo live-imaging model in the rat optic nerve using viral vector mediated LC3-labeling and two-photon-microscopy to analyze axonal transport of AVs. Under basal conditions in vivo, 50% of the AVs are moving with a majority of 85% being transported in the retrograde direction. Transport velocity is higher in the retrograde than in the anterograde direction. A crush lesion of the optic nerve results in a rapid breakdown of retrograde axonal transport while the anterograde transport stays intact over several hours. Close to the lesion site, the formation of AVs is upregulated within the first 6 h after crush, but the clearance of AVs and the levels of lysosomal markers in the adjacent axon are reduced. Expression of p150Glued, an adaptor protein of dynein, is significantly reduced after crush lesion. In vitro, fusion and colocalization of the lysosomal marker cathepsin D with AVs are reduced after axotomy. Taken together, we present here the first in vivo analysis of axonal AV transport in the mammalian CNS using live-imaging. We find that axotomy leads to severe defects of retrograde motility and a decreased clearance of AVs via the lysosomal system.

The Role of Axonal Transport in Glaucoma.

Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs) and leads to progressive vision loss. The first pathological signs can be seen at the optic nerve head (ONH), the structure where RGC axons leave the retina to compose the optic nerve. Besides damage of the axonal cytoskeleton, axonal transport deficits at the ONH have been described as an important feature of glaucoma. Axonal transport is essential for proper neuronal function, including transport of organelles, synaptic components, vesicles, and neurotrophic factors. Impairment of axonal transport has been related to several neurodegenerative conditions. Studies on axonal transport in glaucoma include analysis in different animal models and in humans, and indicate that its failure happens mainly in the ONH and early in disease progression, preceding axonal and somal degeneration. Thus, a better understanding of the role of axonal transport in glaucoma is not only pivotal to decipher disease mechanisms but could also enable early therapies that might prevent irreversible neuronal damage at an early time point. In this review we present the current evidence of axonal transport impairment in glaucomatous neurodegeneration and summarize the methods employed to evaluate transport in this disease.

Transcriptomic Characterization of the Effects of Selenium on Maize Seedling Growth.

Selenium (Se) is a trace mineral element in soils that can be beneficial to plants in small amounts. Although maize is among the most economically important crops, there are few reports on the effects of Se on maize seedling growth at the molecular level. In this study, the growth of maize seedlings treated with different concentrations of Na2SeO3 was investigated, and the physiological characteristics were measured. Compared with the control, a low Se concentration promoted seedling growth, whereas a high Se concentration inhibited it. To illustrate the transcriptional effects of Se on maize seedling growth, samples from control plants and those treated with low or high concentrations of Se were subjected to RNA sequencing. The differentially expressed gene (DEG) analysis revealed that there were 239 upregulated and 106 downregulated genes in the low Se treatment groups, while there were 845 upregulated and 1,686 downregulated DEGs in the high Se treatment groups. Both the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses showed a low concentration of the Se-stimulated expression of "DNA replication" and "glutathione (GSH) metabolism"-related genes. A high concentration of Se repressed the expression of auxin signal transduction and lignin biosynthesis-related genes. The real-time quantitative reverse transcription PCR (qRT-PCR) results showed that in the low Se treatment, "auxin signal transduction," "DNA replication," and lignin biosynthesis-related genes were upregulated 1.4- to 57.68-fold compared to the control, while, in the high Se concentration treatment, auxin signal transduction and lignin biosynthesis-related genes were downregulated 1.6- to 16.23-fold compared to the control. Based on these transcriptional differences and qRT-PCR validation, it was found that a low dosage of Se may promote maize seedling growth but becomes inhibitory to growth at higher concentrations. This study lays a foundation for the mechanisms underlying the effects of Se on maize seedling growth.

Lipid Profile in Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

Background: Studies have investigated the lipid profile in amyotrophic lateral sclerosis (ALS), including the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and higher low-density lipoprotein (LDL), and the associations with mortality of ALS, but the results were inconsistent. Therefore, we conducted this meta-analysis to systematically answer this unsolved question. Methods: We searched all the related studies that probed into the association between serum lipid levels and ALS based on PubMed, EMBASE, and Cochrane library from January 1990 to July 2020. The quality of the included studies was evaluated by using the Newcastle-Ottawa Scale (NOS). All the statistical analyses of this meta-analysis were performed using the Stata version 12.0 software. Results: Fourteen studies with a total of 3,291 ALS patients and 3,367 controls were included. Among them, 10 studies compared the lipid profile between ALS patients and controls. The results indicated that compared with controls, ALS patients from both Europe and Asia had lower levels of TG and HDL, but the levels of TC and LDL were higher in ALS patients from Europe. However, after systemic analyses, the altered TC level was significant only in Asian ALS patients; the differences of other lipids were not significant. Concerning the effect of lipid profile on mortality of ALS, analyses of four cohort studies showed that the levels of all lipids were not associated with overall mortality in ALS. Conclusion: The results of the present study showed that Asian ALS patients had lower TC levels than controls, and the levels of all lipids were not associated with mortality of ALS.

Effects of Higher Serum Lipid Levels on the Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background: The causal relationship between serum lipid levels and the risk of Parkinson's disease (PD) remains largely uncertain. We summarized the existing controversial evidence on this topic. Methods: We searched the electronic databases for observational studies from January 1988 to March 2020. We applied random-effects models to calculate pooled relative risk (RR) with their 95% confidence intervals (CI). Random-effects dose-response meta-analyses were further conducted to explore the dose-risk relationship. Results: Twelve cohort studies and three case-control studies were included in this meta-analysis. Higher levels of serum low-density lipoprotein cholesterol (LDL-C) were inversely associated with the subsequent risk of PD (RR 0.73, 95% CI 0.57-0.93), whereas, there were no associations between serum levels of total cholesterol (TC) (RR 0.91, 95% CI 0.73-1.13), high-density lipoprotein cholesterol (HDL-C) (RR 0.97, 95% CI 0.73-1.27), or triglycerides (TG) (RR 0.85, 95% CI 0.55-1.29) and the risk of PD. Further dose-response meta-analysis revealed that every 38.6 mg/dL (1mmol/L) increase in serum LDL-C correlates with a 7% decreased risk of PD. Conclusions: Our paper supports the protective effect of higher serum LDL-C on the subsequent risk of PD. More prospective cohort studies are warranted to confirm the conclusion, and further fundamental researches are needed to elucidate the underlying biological mechanisms.

Serum creatinine levels in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.

BACKGROUND: Serum creatinine (Cr) is a biosynthetic product of creatine phosphate metabolism in muscles and is closely related to total muscle mass, but it is not easily affected by diet. Several studies have tried to explore the role of serum Cr levels in amyotrophic lateral sclerosis (ALS), but the results were inconsistent. Therefore, our study aims to explore the differences of serum Cr levels between ALS patients and controls and whether serum Cr at baseline is an independent predictor of survival. Methods: We searched all the related studies that probed into the association between Serum Cr levels and ALS based on PubMed, EMBASE and Cochrane library from October 1952 to February 2019. The quality of the included studies was evaluated by using Newcastle-Ottawa Scale (NOS), and all the statistical analysis of this meta-analysis was performed by Stata version 12.0. Results: Eight studies with a total of 11377 ALS patients and 937 controls were included. Among them, five studies indicated that ALS patients had lower serum Cr levels (SMD = -0.78, 95%CI [-0.97, -0.60]) compared to controls, and three studies showed that higher serum Cr levels in ALS patients were related to lower overall mortality (HR 0.89, 95%CI [0.80, 0.99]). Conclusion: The levels of serum Cr in ALS patients are significantly lower than those in controls, and they are inversely related to overall mortality in ALS patients. Therefore, the serum Cr, an easily accessible serological factor, may serve as a prognostic biomarker.

Association Between Serum Vitamin D Levels and Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background: Vitamin D is an important secosteroid which is involved the development and regulation of brain activity. Several studies have focused on exploring the relationship between serum vitamin D levels and Parkinson's disease (PD), but the conclusion remains ambiguous. Methods: We searched observational studies that explored the association between serum vitamin D levels and PD based on PubMed, EMBASE and Cochrane library from inception through to January 2018. The quality of included studies was evaluated by using Newcastle-Ottawa Scale (NOS). Statistical analysis of this meta-analysis was performed by Stata version 12.0 and R software. Results: Twenty studies with a total of 2,866 PD patients and 2,734 controls were included. Compared with controls, PD patients had lower serum vitamin D levels (WMD -3.96, 95%CI -5.00, -2.92), especially in higher latitude regions (WMD -4.20, 95%CI -5.66, -2.75). Assay methods contributed significantly to high heterogeneity. Furthermore, PD patients with deficient vitamin D levels had advanced risk (OR 2.08, 95%CI 1.35, 3.19) than those patients with insufficient ones (OR = 1.73, 95%CI 1.48, 2.03). In addition, serum vitamin D levels were also related to the severity of PD (WMD -5.27, 95%CI -8.14, -2.39) and the summary correlation coefficient showed strongly negative correlation (r = -0.55, 95%CI -0.73, -0.29). Moreover, the pooled correlation coefficient revealed that serum vitamin D levels were also negatively correlated to the Unified Parkinson's Disease Rating Scale III (UPDRS III) (r = -0.36, 95%CI -0.53, -0.16), but did not correlate with the duration of PD (P = 0.37) and age of patients (P = 0.49). Conclusion: Serum vitamin D levels are inversely associated with the risk and severity of PD. Our results provided an updated evidence of association between low vitamin D levels and PD and prompt the adjunctive therapeutic decisions about vitamin D replacement in PD.