Glutamate-mediated neurodegeneration resulting from excessive activation of glutamate receptors is recognized as one of the major causes of various neurological disorders such as Alzheimer's and Huntington's diseases. However, the underlying mechanisms in the neurodegenerative process remain unidentified. Here, we investigate the real-time dynamic structural and mechanical changes associated with the neurodegeneration induced by the activation of N-methyl-D-aspartate (NMDA) receptors (a subtype of glutamate receptors) at the nanoscale. Atomic force microscopy (AFM) is employed to measure the three-dimensional (3-D) topography and mechanical properties of live SH-SY5Y cells under stimulus of NMDA receptors. A significant increase in surface roughness and stiffness of the cell is observed after NMDA treatment, which indicates the time-dependent neuronal cell behavior under NMDA-mediated neurodegeneration. The present AFM based study further advance our understanding of the neurodegenerative process to elucidate the pathways and mechanisms that govern NMDA induced neurodegeneration, so as to facilitate the development of novel therapeutic strategies for neurodegenerative diseases.
Parkinson's disease is caused by the degeneration of dopaminergic neurons in substantia nigra. There is no current promising treatment for neuroprotection of dopaminergic neurons. Ceftriaxone is a beta-lactam antibiotic and has been reported to offer neuroprotective effects (Rothstein, J.-D., Patel, S., Regan, M.-R., Haenggeli, C., Huang, Y.-H., Bergles, D.-E., Jin, L., Dykes, H.-M., Vidensky, S., Chung, D.-S., Toan, S.-V., Bruijn, L.-I., Su, Z.-Z., Gupta, P., and Fisher, P.-B. (2005) Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression Nature433, 73-77). In the present study, efficacy of ceftriaxone in neuroprotection of dopaminergic neurons and amelioration of motor deficits in a rat model of Parkinson's disease were investigated. Ceftriaxone was administrated in 6-hydroxydopamine-lesioned rats. Using behavioral tests, grip strength and numbers of apomorphine-induced contralateral rotation were declined in the ceftriaxone-treated group. More importantly, cell death of dopaminergic neurons was found to decrease. In addition, both the protein expression and immunoreactivity for GLT-1 were up-regulated. The present results strongly indicate that ceftriaxone is a potential agent in the treatment of Parkinson's disease.
Despite a variety of T1–T2 dual-modal contrast agents (DMCAs) reported for magnetic resonance imaging (MRI), no tuning of local induced magnetic field strength of an DMCA, which is important to modulate the overall T1 and T2 responses for imaging delicate cells, tissues, and organs, is yet available. Here, we show that a spatial arrangement of T1 and T2 components within a “nano zone” in a single core–shell nanoparticle carrier (i.e., DMCA with core Fe3O4 and MnO clusters in a silica shell) to produce the necessary fine-tuning effect. It is demonstrated that this particle after the anti-CD133 antibody immobilization allows both T1 and T2 imaging at higher resolution for living ependynmal brain cells of rodents with no local damage under a strong MRI magnetic field. This study opens a route to rational engineering of DMCAs for accurate magnetic manipulations in a safe manner.
Neural stem cells (NSCs), which generate the main phenotypes of the nervous system, are multipotent cells and are able to differentiate into multiple cell types via external stimuli from the environment. The extraction, modification and re-application of NSCs have thus attracted much attention and raised hopes for novel neural stem cell therapies and regenerative medicine. However, few studies have successfully identified the distribution of NSCs in a live brain and monitored the corresponding extraction processes both in vitro and in vivo. To address those difficulties, in this study multi-functional uniform nanoparticles comprising an iron oxide core and a functionalized silica shell (Fe(3)O(4)@SiO(2)(FITC)-CD133, FITC: a green emissive dye, CD133: anti-CD133 antibody) have been strategically designed and synthesized for use as probe nanocomposites that provide four-in-one functionality, i.e., magnetic agitation, dual imaging (both magnetic resonance and optical) and specific targeting. It is shown that these newly synthesized Fe(3)O(4)@SiO(2)(FITC)-CD133 particles have clearly demonstrated their versatility in various applications. (1) The magnetic core enables magnetic cell collection and T(2) magnetic resonance imaging. (2) The fluorescent FITC embedded in the silica framework enables optical imaging. (3) CD133 anchored on the outermost surface is demonstrated to be capable of targeting neural stem cells for cell collection and bimodal imaging.
It stems from the magnetism: The extraction of stem/progenitor cells from the brain of live animals is possible using antibodies conjugated to magnetic nanoparticles (Ab-MNPs). The Ab-MNPs are introduced to a rat's brain with a superfine micro-syringe. The stem cells attach to the Ab-MNPs and are magnetically isolated and removed. They can develop into neurospheres and differentiate into different types of cells outside the subject body. The rat remains alive and healthy.
BackgroundThe present study investigates the effects of ginsenosides Rh1 and Rg2 against 6-hydroxydopamine (6-OHDA), a neurotoxin on SH-SY5Y cells and PC-12 cells. The effects of these two ginsenosides on neuronal differentiation are also examined.MethodsLDH assay was used to measure cell viability after exposure to 6-OHDA and ginsenosides. Neuronal differentiation was evaluated by changes in cell morphology and density of neurite outgrowths. Western blotting was used to determine the ginsenosides' effects on activation of extracellular signal-regulated protein kinases (ERKs).ResultsRh1 and Rg2 attenuated 6-OHDA toxicity in SH-SY5Y cells and induced neurite outgrowths in PC-12 cells. 6-OHDA-induced ERK phosphorylation was decreased by Rh1 and Rg2. 20(R)-form and 20(S)-form of the ginsenosides exerted similar effects in inducing neurite outgrowths in PC-12 cells.ConclusionThe present study demonstrates neuroprotective effects of ginsenosides Rh1 and Rg2 on neuronal cell lines. These results suggest potential Chinese medicine treatment for neurodegenerative disorders (eg Parkinson's disease).
Aus dem Gehirn lebender Tiere können Stamm‐/Vorläuferzellen mithilfe von Antikörperkonjugaten magnetischer Nanopartikel (Ab‐MNPs) extrahiert werden. Wenn Ab‐MNPs in Rattengehirn injiziert werden, lagern sich die Stammzellen an diese an und können auf magnetischem Weg isoliert werden. Außerhalb des Körpers können sie sich zu Neurosphären entwickeln und zu verschiedenen Zellarten differenzieren, während die Ratten gesund weiterleben.
The prevalence of multiple neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), has been dramatically increasing, particularly in the aging population. However, the currently available therapies merely alleviate the symptoms of these diseases and are unable to retard disease progression significantly. Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years for ameliorating symptoms or interfering with the pathogenesis of aging- associated diseases. Modern pharmacological studies have proved that TCM imparts disease-modifying therapeutic effects against these diseases, such as protection of neurons, clearance of protein aggregates, and regulation of neuroinflammation. This review summarizes the evidence from recent studies on AD and PD therapies regarding the neuroprotective activities and molecular mechanisms of a series of TCM formulations comprising herbs and their active ingredients. The findings of this review support the use of TCM as an alternative source of therapy for the treatment of neurodegenerative diseases.
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