Neuronal autophagy and neurodegenerative diseases

Autophagy is a dynamic cellular pathway involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. The integrity of postmitotic neurons is heavily dependent on high basal autophagy compared to non-neuronal cells as misfolded proteins and damaged organelles cannot be diluted through cell division. Moreover, neurons contain the specialized structures for intercellular communication, such as axons, dendrites and synapses, which require the reciprocal transport of proteins, organelles and autophagosomes over significant distances from the soma. Defects in autophagy affect the intercellular communication and subsequently, contributing to neurodegeneration. The presence of abnormal autophagic activity is frequently observed in selective neuronal populations afflicted in common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. These observations have provoked controversy regarding whether the increase in autophagosomes observed in the degenerating neurons play a protective role or instead contribute to pathogenic neuronal cell death. It is still unknown what factors may determine whether active autophagy is beneficial or pathogenic during neurodegeneration. In this review, we consider both the normal and pathophysiological roles of neuronal autophagy and its potential therapeutic implications for common neurodegenerative diseases.     

Conducting swift heavy ion track networks

In this paper, the electronic behavior of conducting swift heavy ion track networks is studied. On the one hand, the transient conductivity of ion tracks in metal oxides on silicon in status nascendi is exploited for this purpose, and on the other hand, conducting tracks are produced by ion irradiation of insulating membranes (either self-supported or deposited onto silicon substrates), subsequent etching and finally inserting conducting materials of whatever provenience (in this work preferentially electrolytes). Depending on their manufacture, the conducting tracks either act as electronically active or passive elements. When applying a voltage across individual tracks in the first case, one observes current spikes with negative differential resistances. These tracks interact among themselves, leading to phase-locked synchronous coupled oscillations with complex patterns that are quite similar to those emerging from neural networks. The other case corresponds to networks of electronically passive conducting tracks which become overall electronically active only through their collective interactions. Though the aforementioned effects had been experimentally described earlier, they are re-visited here to make clear that the corresponding systems have to be considered as being artificial neural networks. On this occasion, some new findings are added.     

关于周期神经网络逼近阶的研究

借助于有关Fourier级数的Riesz平均构造出了一类含有一个隐含层的周期神经网络与平移网络,与已有的讨论相比较,在获得相同的逼近阶的情况下,此类网络的隐层单元要求较少的神经元个数.     

LMI-based robust adaptive synchronization of FitzHugh-Nagumo neurons with unknown parameters under uncertain external electrical stimulation

This Letter addresses a nonlinear robust adaptive control that utilizes linear matrix inequalities for asymptotic synchronization of two coupled chaotic FitzHugh-Nagumo neurons under unknown parameters and uncertain stimulation current amplitudes and phase shifts. Synchronization of chaotic neurons using the proposed control method through numerical simulation is demonstrated.     

Senescent Phenotype of Astrocytes Leads to Activation of BV2 Microglia and N2a Neuronal Cells Death

(1) Background: Astrocytes, the most abundant cell type in the central nervous system, are essential to tune individual-to-network neuronal activity. Senescence in astrocytes has been discovered as a crucial contributor to several age-related neurological diseases. Here, we aim to observe if astrocytes demonstrate senescence in the process of brain aging, and whether they bring adverse factors, especially harm to neuronal cells. (2) Methods: In vivo, mice were housed for four, 18, and 26 months. An in vitro cell model of aged astrocytes was constructed by serial passaging until passage 20–25, and those within 1–5 were invoked as young astrocytes. Meanwhile, an oxidative induced astrocyte senescence model was constructed by H₂O₂ induction. (3) Results: In vitro aged astrocytes all showed manifest changes in several established markers of cellular senescence, e.g., P53, P21, and the release of inflammatory cytokine IL-6 and SA-β-gal positive cells. Results also showed mitochondrial dysfunction in the oxidative stress-induced astrocyte senescence model and treatment of berberine could ameliorate these alterations. Two types of senescent astrocytes’ conditioned medium could impact on neuron apoptosis in direct or indirect ways. (4) Conclusions: Senescent astrocyte might affect neurons directly or indirectly acting on the regulation of normal and pathological brain aging.     

Quercetin-albumin nano-complex as an antioxidant agent against hydrogen peroxide-induced death of spinal cord neurons as a model of preventive care study

Herein, the quercetin-human serum albumin (HSA) nano-complex was formulated and its capability to decrease H₂O₂-stimulated cytotoxicity against spinal cord neurons as a model of preventive care study was investigated by cellular assays. Quercetin molecules were first encapsulated into HSA as a shell and the loading efficiency along with drug release and different properties of formulated nano-complex were determined using TEM, SEM, and DLS approaches. Afterwards using CD spectroscopic method and theoritical analysis, the structural changes and binding redisues of HSA after interaction with quercetin were investigated, respectively. Finally, the antioxidant activity of quercetin-HSA nano-complex against H₂O₂ (200 µM)-stimulated cytotoxicity in spinal cord neurons was explored by MTT, SOD and CAT activity, and morphological changes assays. It was shown that the fabrication of quercetin-HSA nano-complex resulted in the improved bioavailability of quercetin with an entrapment efficiency of 68.99% and percent yield of 53.19%. Also, molecular docking study showed that quercetin molecules spontaneously bind to HSA through hydrogen bonds and van der Waals interactions. Furthermore, CD data indicated that the quercetin did not change the secondary structure of HSA. Finally, cellular assays displayed that the pre-treatments of spinal cord neurons with quercetin-HSA nano-complex attenuated the H₂O₂-triggerd neuron mortality through a significant increase in the activity of SOD and CAT and prevention of morphological changes. In conclusion, it may be suggested that the formulation of quercetin into nano-complex can improve its medical properties and this new developed drug formulation may hold a great promise in the advancement of antioxidant compounds in preventive care services.     

Examples of Scientific Problems and Data Analyses in Demography,Neurophysiology, and Seismology

Examples of scientific problems and data analyses are presented for the fields of demography, neurophysiology, and seismology. The examples are connected by the involvement of space or time. The demographic problem is to display quantities derived from spatially aggregated data and associated measures of uncertainty. The neurophysiological problem is to infer the presence of complex pathways among groups of neurons given sequences of firing times. There are two seismological problems: (1) to determine isoseismals of recorded intensities following the Loma Prieta earthquake and (2) to relate intensity and acceleration values measured at distinct locations. The statistical analyses are connected to each other by the application of smoothing in some form and by the provision of consequent graphical displays.     

The roles of glycosphingolipids in the proliferation and neural differentiation of mouse embryonic stem cells

Glycosphingolipids including gangliosides play important regulatory roles in cell proliferation and differentiation. UDP-glucose:ceramide glucosyltransferase (Ugcg) catalyze the initial step in glycosphingolipids biosynthesis pathway. In this study, Ugcg expression was reduced to approximately 80% by short hairpin RNAs (shRNAs) to evaluate the roles of glycosphingolipids in proliferation and neural differentiation of mouse embryonic stem cells (mESCs). HPTLC/immunofluorescence analyses of shRNA-transfected mESCs revealed that treatment with Ugcg-shRNA decreased expression of major gangliosides, GM3 and GD3. Furthermore, MTT and Western blot/immunofluorescence analyses demonstrated that inhibition of the Ugcg expression in mESCs resulted in decrease of cell proliferation (P < 0.05) and decrease of activation of the ERK1/2 (P < 0.05), respectively. To further investigate the role of glycosphingolipids in neural differentiation, the embryoid bodies formed from Ugcg-shRNA transfected mESCs were differentiated into neural cells by treatment with retinoic acid. We found that inhibition of Ugcg expression did not affect embryoid body (EB) differentiation, as judged by morphological comparison and expression of early neural precursor cell marker, nestin, in differentiated EBs. However, RT-PCR/immunofluorescence analyses showed that expression of microtubule- associated protein 2 (MAP-2) for neurons and glial fibrillary acidic protein (GFAP) for glial cells was decreased in neural cells differentiated from the shRNA-transfected mESCs. These results suggest that glycosphingolipids are involved in the proliferation of mESCs through ERK1/2 activation, and that glycosphingolipids play roles in differentiation of neural precursor cells derived from mESCs.