Glioblastoma multiforme (GBM) is paradigmatic for the investigation of cancer stem cells (CSC) in solid tumors. Growing evidence suggests that different types of CSC lead to the formation of GBM. This has prompted the present comparison of gene expression profiles between 17 GBM CSC lines and their different putative founder cells.
View Article and Find Full Text PDFBeck depression inventory (BDI-1A) is the gold standard screening tool for Parkinson's disease (PD) depression, but as a result of its complexity, it is of limited suitability as a quick and easy screening device. We, therefore, validate the 5-item WHO-Five Well-being Index (WHO-5) as a screening tool for PD depression. Two hundred thirteen of 215 recruited PD patients (99.
View Article and Find Full Text PDFThe aim of this study was to investigate the effect of oxidative stress on mitochondrial phospholipids. In this context, this study investigated (i) the content of phosphatidylethanolamine (PE), phosphatidylcholine (PC) and cardiolipin (CL), (ii) the correlation of CL degradation with mitochondrial function and (iii) the correlation of CL degradation and CL oxidation. Oxidative stress induced by iron/ascorbate caused a dramatic decrease of these phospholipids, in which CL was the most sensitive phospholipid.
View Article and Find Full Text PDFBackground: Treadmill training is used in rehabilitation and is described as improving gait parameters of patients with Parkinson's disease.
Objectives: To assess the effectiveness of treadmill training in improving the gait function of patients with Parkinson's disease and the acceptability and safety of this type of therapy.
Search Strategy: We searched the Cochrane Movement Disorders Group Specialised Register (see Review Group details for more information) (last searched March 2009), Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 2), MEDLINE (1950 to March 2009), and EMBASE (1980 to March 2009).
Background Aims: Human adult bone marrow (BM)-derived mesenchymal stromal cells (hMSC) are reported to break germ layer commitment and differentiate into cells expressing neuroectodermal properties. Although it is of pivotal interest for cell replacement therapies for neurologic disorders, no data exist on the influence of the donor's age on this multipotent differentiation behavior.
Methods: We evaluated various epigenetic neuroectodermal conversion protocols in adult hMSC derived from older donors (>45 versus 18-35 years of age) using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunocytochemistry.
The nanoscale spatial organization of collagen fibrils as major constituents of extracellular matrices is believed to be crucial for neurite guidance in neural development and repair. To systematically study the influence of collagen fibril alignment, length, and density on human neuronal cell behavior, we used our novel technology to produce aligned collagen matrices by shear flow deposition using a microfluidic channel system and applied these surfaces to functional human neurons and glia derived from white matter neural stem cell cultures. Neurites on aligned collagen were highly oriented in the direction of the underlying fibrils, whereas neurites on nonaligned collagen or poly-d-lysine did not exhibit a preferred direction but formed a web-like morphology.
View Article and Find Full Text PDFParkinson's disease (PD) is a progressive neurodegenerative movement disorder and is characterized by a continuous and selective loss of dopaminergic neurons in the midbrain with a subsequent reduction of the neurotransmitter dopamine in the striatum. Strategies to overcome limitations of conventional symptomatic treatment have employed cell-based strategies including transplantation of developing neural tissue or neural stem cells (NSCs) into the degenerated host brain. Still there is a tug of war for determining the ideal cell source for transplantation strategies.
View Article and Find Full Text PDFJ Neural Transm (Vienna)
November 2009
Parkinson's disease (PD) is the second most common neurodegenerative disease and primarily considered as a movement disorder defined by the presence of motor symptoms, such as bradykinesia, tremor and rigidity. However, it is nowadays widely accepted that PD is associated with a wide variety of non-motor features, which affect the vast majority of patients during the course of the disease and may even precede the onset of motor symptoms. The spectrum of these non-motor disturbances is very broad and comprises neuropsychiatric conditions, such as depression, dementia and hallucinations, as well as autonomic, sensory and sleep disorders.
View Article and Find Full Text PDFChromaffin cells of the adrenal medulla are neural crest-derived cells of the sympathoadrenal lineage. Unlike the closely-related sympathetic neurons, a subpopulation of proliferation-competent cells exists even in the adult. Here, we describe the isolation, expansion, and in vitro characterization of proliferation-competent progenitor cells from the bovine adrenal medulla.
View Article and Find Full Text PDFBackground: 'Dropped head' and 'bent spine' phenomena are recognized clinical presentations of neuromuscular disorders. Similar symptoms are known in patients with parkinsonian syndromes, but their pathophysiology remains unclear. One hypothesis is a relation between the movement disorder and the skeletal muscle pathology.
View Article and Find Full Text PDFBiofunctional matrices for in vivo tissue engineering strategies must be modifiable in both biomolecular composition and mechanical characteristics. To address this challenge, we present a modular system of biohybrid hydrogels based on covalently cross-linked heparin and star-shaped poly(ethylene glycols) (star-PEG) in which network characteristics can be gradually varied while heparin contents remain constant. Mesh size, swelling and elastic moduli were shown to correlate well with the degree of gel component cross-linking.
View Article and Find Full Text PDFInterleukin-1 (IL-1) plays a pivotal role in terminal dopaminergic differentiation of midbrain-derived neural precursor cells already committed to the mesencephalic dopaminergic phenotype (named mdNPCs for mesencephalic dopaminergic neural precursor cells). Here we characterized the molecular events in long-term expanded rat nuclear receptor related-1(-) (Nurr1(-)) mdNPCs in response to IL-1beta during their terminal dopaminergic specification. We showed that IL-1beta induced a rapid induction of mRNA of dopaminergic key fate-determining transcription factors, such as Nurr1 and Pitx3, and a subsequent increase of tyrosine hydroxylase protein as an early marker for dopaminergic neurons in vitro.
View Article and Find Full Text PDFNeural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Administration of NSCs into the cerebrospinal fluid (CSF) offers a nontraumatic transplantation method into the brain. However, cell survival and intraparenchymal migration of the transplants are limited.
View Article and Find Full Text PDFDespite a comprehensive mapping of the Parkinson's disease (PD)-related mRNA and protein leucine-rich repeat kinase 2 (LRRK2) in the mammalian brain, its physiological function in healthy individuals remains enigmatic. Based on its structural features and kinase properties, LRRK2 may interact with other proteins involved in signalling pathways. Here, we show a widespread LRRK2 mRNA and/or protein expression in expanded or differentiated human mesencephalic neural progenitor cells (hmNPCs) and in post-mortem substantia nigra PD patients.
View Article and Find Full Text PDFMost disease-modifying therapeutic approaches in Alzheimer's disease (AD) aim to reduce the accumulation of neurotoxic amyloid-beta (Abeta) peptides as a hallmark of AD pathogenesis. Here we report the in vitro basis for a potential autologous stem cell-based strategy for widespread delivery of enzymatic activities against Abeta formation in the brain. We detected the functional induction of two genes upon neuroectodermal conversion of human adult mesenchymal stem cells (MSCs), namely F-spondin and neprilysin (CD10), with a 4,992 + or - 697-fold and 692 + or - 226-fold increase of mRNA levels in converted cells compared to MSCs, respectively (n = 3; P < 0.
View Article and Find Full Text PDFParkinsonism Relat Disord
September 2009
Objective: To assess the effect of a single levodopa dose (200 mg levodopa, 50 mg carbidopa=sdLD) on cortical and subcortical motor-circuit activation during bimanual grip force in patients with Parkinson's disease (PD).
Patients And Methods: We studied 12 right-handed patients with PD (Hoehn-Yahr stages I-II) after a period of at least 12 h without medication (OFF state) and a second time 1 h after oral administration of sdLD (ON state) using functional magnetic resonance imaging (fMRI). Blood-oxygenation-level-dependency (BOLD) fMRI was measured while participants underwent two unilateral and two bimanual grip force movements with a defined movement amplitude and force (10N) in a block design.
Hypoxia-inducible factor-1 (HIF-1) plays an important role in neural progenitor cell (NPC) propagation and dopaminergic differentiation. In the presence of oxygen and iron, hypoxia-inducible factor 1 alpha (HIF-1alpha) is rapidly degraded via the prolyl hydroxylase (PHD)/VHL pathway. In addition to hypoxia, various non-hypoxic stimuli can stabilize HIF-1alpha in NPCs and influence the transcription of HIF-regulated genes.
View Article and Find Full Text PDFNeurogenesis occurs constitutively within the periventricular region (PVR) of the lateral ventricles (LV) of the adult mammalian brain. The occurrence of adult neurogenesis within the PVR outside the neurogenic niche of the LV remains controversial, but neural stem cells can be isolated from PVR of the whole ventricular system. The histological basis of this phenomenon including the regional differences of cellular phenotypes within the PVRs is still enigmatic.
View Article and Find Full Text PDFClinical observations in Parkinson's disease (PD) patients suggested an increased chocolate consumption. Chocolate contains high contents of various biogenic amines potentially influencing brain monoamine metabolism. 498 PD patients and their partners were evaluated by a structured self-questionnaire asking for consumption of chocolate and non-chocolate sweets, changes in chocolate consumption during the disease course, and depressive symptoms.
View Article and Find Full Text PDFTwo small studies reported suboptimal therapy adherence in Parkinson's disease. We conducted a larger multicenter European study to assess medicine-taking behavior. Parkinson's disease patients taking dopaminergic therapy were enrolled in 8 centers in 5 countries, and disease severity and demographics recorded.
View Article and Find Full Text PDFHuman neural progenitor cells (hNPCs) are a promising source to treat various neurodegenerative diseases. Potential applications are to use such cells for reprogramming to induce pluripotent stem cells or for secretion of proteins into the brain. These applications usually involve expression of heterologously expressed genes which is difficult to achieve in hNPCs.
View Article and Find Full Text PDFBackground: Bone marrow (BM)-derived mesenchymal stromal cells (MSC) are promising candidate cells for the development of neuroregenerative therapies. We have previously introduced the pro-neural conversion of human MSC to neural stem cell-like cells (m-NSC) by culturing them in suspension culture under serum-free conditions.
Methods: In the present study, we used a modified Boyden chamber assay to study the influence of various chemoattractants and extracellular matrix components on MSC and m-NSC migration in vitro.