Previous studies have conifrmed that the beclin 1 complex plays a key role in the initial stage of autophagy and deregulated autophagy might involve in amyotrophic lateral sclerosis. However, the mechanism underlying altered autophagy associated with the beclin 1 complex remains un-clear. In this study, we transfected the Cu/Zn superoxide dismutase 1 G93A mutant protein into the motor neuron-like cell line NSC34 cultured in vitro. Western blotting and co-immunopre-cipitation showed that the Cu/Zn superoxide dismutase 1 G93A mutant enhanced the turnover of autophagic marker microtubule-associated protein light chain 3II (LC3II) and stimulated the conversion of EGFP-LC3I to EGFP-LC3II, but had little inlfuence on the binding capacity of the autophagy modulators ATG14L, rubicon, UVRAG, and hVps34 to beclin 1 during auto-phagosome formation. These results suggest that the amyotrophic lateral sclerosis-linked Cu/Zn superoxide dismutase 1 G93A mutant can upregulate autophagic activity in NSC34 cells, but that this does not markedly affect beclin 1 complex components.

The Chinese compound Kaixin Jieyu Fang can be used to treat vascular depression;however, the underlying mechanism remains unclear. This study established a rat model of chronic cerebral ischemia-caused white matter damage by ligation of the bilateral common carotid arteries. Rats received daily intragastric administration of a suspension of Kaixin Jieyu Fang powder. After 3, 7 and 21 days of treatment, the degree of white matter damage in the cerebral ischemia rat model was alleviated, Bcl-2 protein and mRNA expression in brain tissue increased, and Bax protein and mRNA expression decreased. These results indicate that Kaixin Jieyu Fang can alleviate cere-bral white matter damage, and the underlying mechanism is associated with regulation of Bcl-2/Bax protein and mRNA expression, which is one of possible mechanism behind the protective effect of Kaixin Jieyu Fang against vascular depression.

To date, it remains poorly understood whether astrocytes can be easily reprogrammed into neurons. Mash1 and Brn2 have been previously shown to cooperate to reprogram fibroblasts into neurons. In this study, we examined astrocytes from 2-month-old Sprague-Dawley rats, and found that Brn2 was expressed, but Mash1 was not detectable. Thus, we hypothesized that Mash1 alone could be used to reprogram astrocytes into neurons. We transfected a recombinant MSCV-MASH1 plasmid into astrocytes for 72 hours, and saw that all cells expressed Mash1. One week later, we observed the changes in morphology of astrocytes, which showed typical neuro-nal characteristics. Moreover,β-tubulin expression levels were signiifcantly higher in astrocytes expressing Mash1 than in control cells. These results indicate that Mash1 alone can reprogram astrocytes into neurons.

Studies have shown that functional network connection models can be used to study brain net-work changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their ifrst ever stroke. Using independent component analysis, six spatially independent components highly correlat-ed to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our ifndings suggest that functional network connectivity in stroke patients is more complex than that in hea-lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke.

Transforming growth factor-beta (TGF-β) type II receptor (TβRII) levels are extremely low in the brain tissue of patients with Alzheimer’s disease. This receptor inhibits TGF-β1/SMAD signaling and thereby aggravates amyolid-beta deposition and neuronal injury. Dab2, a speciifc adapter protein, protects TβRII from degradation and ensures the effective conduction of TGF-β1/SMAD signaling. In this study, we used an adenoviral vector to overexpress the Dab2 gene in the mouse hippocampus and investigated the regulatory effect of Dab2 protein on TGF-β1/SMAD signaling in a mouse model of Alzheimer’s disease, and the potential neuroprotective effect. The results showed that the TβRII level was lower in APP/PS1 mouse hippocampus than in normal mouse hippocampus. After Dab2 expression, hippocampal TβRII and p-SMAD2/3 levels were signiif-cantly increased, while amyloid-beta deposition, microglia activation, tumor necrosis factor-βand interleulin-6 levels and neuronal loss were signiifcantly attenuated in APP/PS1 mouse brain tissue. These results suggest that Dab2 can exhibit neuroprotective effects in Alzheimer’s disease by regulating TGF-β1/SMAD signaling.

Glial cell line-derived neurotrophic factor recombinant adenovirus vector-transfected bone marrow mesenchymal stem cells were induced to differentiate into neuron-like cells using inductive medium containing retinoic acid and epidermal growth factor. Cell viability, micro-tubule-associated protein 2-positive cell ratio, and the expression levels of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 protein in the su-pernatant were signiifcantly higher in glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells compared with empty virus plasmid-transfected bone marrow mes-enchymal stem cells. Furthermore, microtubule-associated protein 2, glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 mRNA levels in cell pellets were statistically higher in glial cell line-derived neurotrophic factor/bone marrow mesen-chymal stem cells compared with empty virus plasmid-transfected bone marrow mesenchymal stem cells. These results suggest that glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells have a higher rate of induction into neuron-like cells, and this enhanced differentiation into neuron-like cells may be associated with up-regulated expression of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43.

Mesenchymal stem cell transplantation is a novel means of treating cerebral ischemia/reper-fusion, and can promote angiogenesis and neurological functional recovery. Acupuncture at Conception and Governor vessels also has positive effects as a treatment for cerebral ischemia/reperfusion. Therefore, we hypothesized that electro-acupuncture at Conception and Governor vessels plus mesenchymal stem cell transplantation may have better therapeutic effects on the promotion of angiogenesis and recovery of neurological function than either treatment alone. In the present study, human umbilical cord blood-derived mesenchymal stem cells were isolated, cultured, identified and intracranially transplanted into the striatum and subcortex of rats at 24 hours following cerebral ischemia/reperfusion. Subsequently, rats were electro-acupunctured at Conception and Governor vessels at 24 hours after transplantation. Modified neurological severity scores and immunohistochemistry ifndings revealed that the combined interventions of electro-acupuncture and mesenchymal stem cell transplantation clearly improved neurological impairment and up-regulated vascular endothelial growth factor expression around the isch-emic focus. The combined intervention provided a better outcome than mesenchymal stem cell transplantation alone. These ifndings demonstrate that electro-acupuncture at Conception and Governor vessels and mesenchymal stem cell transplantation have synergetic effects on promot-ing neurological function recovery and angiogenesis in rats after cerebral ischemia/reperfusion.

Amyloid-beta peptide is the main component of amyloid plaques, which are found in Alzhei-mer’s disease. The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzheimer’s disease. Lipid rafts are glycolipid-rich liquid domains of the plasma membrane, where certain types of protein tend to aggregate and intercalate. Lipid rafts are involved in the generation of amyloid-beta oligomers and the formation of amyloid-beta peptides. In this paper, we review the mechanism by which lipid rafts disturb the aberrant deg-radative autophagic-lysosomal pathway of amyloid-beta, which plays an important role in the pathological process of Alzheimer’s disease. Moreover, we describe this mechanism from the view of the Two-system Theory of fasciology and thus, suggest that lipid rafts may be a new target of Alzheimer’s disease treatment.

Preliminary basic research and clinical ifndings have demonstrated that electroacupuncture ther-apy exhibits positive effects in ameliorating depression. However, most studies of the underlying mechanism are at the single gene level;there are few reports regarding the mechanism at the whole-genome level. Using a rat genomic gene-chip, we proifled hippocampal gene expression changes in rats after electroacupuncture therapy. Electroacupuncture therapy alleviated depres-sion-related manifestations in the model rats. Using gene-chip analysis, we demonstrated that electroacupuncture at Baihui (DU20) and Yintang (EX-HN3) regulates the expression of 21 genes. Real-time PCR showed that the genes Vg f, Ig f2, Tmp32, Loc500373, Hif1a, Folr1, Nmb, and Rtn were upregulated or downregulated in depression and that their expression tended to nor-malize after electroacupuncture therapy. These results indicate that electroacupuncture at Baihui and Yintang modulates depression by regulating the expression of particular genes.

The apolipoprotein E geneε4 allele is considered a negative factor for neural regeneration in late-onset Alzheimer’s disease cases. The aim of this study was to establish a non-invasive, rapid method to genotype apolipoprotein E gene polymorphisms. Genomic DNA from mouth swab specimens was extracted using magnetic nanoparticles, and genotyping was performed by real-time PCR using TaqMan-BHQ probes. Genotyping accuracy was validated by DNA se-quencing. Our results demonstrate 100%correlation to DNA sequencing, indicating reliability of our protocol. Thus, the method we have developed for apolipoprotein E genotyping is accurate and reliable, and also suitable for genotyping large samples, which may help determine the role of the apolipoprotein Eε4 allele in neural regeneration in late-onset Alzheimer’s disease cases.

Adult mesenchymal stem cells, specifically adipose-derived stem cells have self-renewal and multiple differentiation potentials and have shown to be the ideal candidate for therapeutic applications in regenerative medicine, particularly in peripheral nerve regeneration. Adipose-de-rived stem cells are easily harvested, although they may show the effects of aging, hence their potential in nerve repair may be limited by cellular senescence or donor age. Cellular senescence is a complex process whereby stem cells grow old as consequence of intrinsic events (e.g., DNA damage) or environmental cues (e.g., stressful stimuli or diseases), which determine a permanent growth arrest. Several mechanisms are implicated in stem cell senescence, although no one is exclusive of the others. In this review we report some of the most important factors modulating the senescence process, which can inlfuence adipose-derived stem cell morphology and function, and compromise their clinical application for peripheral nerve regenerative cell therapy.

Critical illness polyneuropathy and critical illness myopathy are frequent complications of severe illness that involve sensorimotor axons and skeletal muscles, respectively. Clinically, they manifest as limb and respiratory muscle weakness. Critical illness polyneuropathy/myopathy in isolation or combination increases intensive care unit morbidity via the inability or dififculty in weaning these patients off mechanical ventilation. Many patients continue to suffer from decreased exercise capacity and compromised quality of life for months to years after the acute event. Substantial progress has been made lately in the understanding of the pathophysiology of critical illness polyneuropathy and myopathy. Clinical and ancillary test results should be carefully interpreted to differentiate critical illness polyneuropathy/myopathy from similar weaknesses in this patient population. The present review is aimed at providing the latest knowledge concerning the pathophysiology of critical illness polyneuropathy/myopathy along with relevant clinical, diagnostic, differentiating, and treatment information for this debilitat-ing neurological disease.