Lentiviral vectors express chondroitinase ABC in cortical projections and promote sprouting of injured corticospinal axons.

Several diseases and injuries of the central nervous system could potentially be treated by delivery of an enzyme, which might most effectively be achieved by gene therapy. In particular, the bacterial enzyme chondroitinase ABC is beneficial in animal models of spinal cord injury. We have adapted the chondroitinase gene so that it can direct secretion of active chondroitinase from mammalian cells, and inserted it into lentiviral vectors.

NG2 expression in glioblastoma identifies an actively proliferating population with an aggressive molecular signature.

Glioblastoma multiforme (GBM) is the most common type of primary brain tumor and a highly malignant and heterogeneous cancer. Current conventional therapies fail to eradicate or curb GBM cell growth. Hence, exploring the cellular and molecular basis of GBM cell growth is vital to develop novel therapeutic approaches.

6-Sulphated chondroitins have a positive influence on axonal regeneration.

Chondroitin sulphate proteoglycans (CSPGs) upregulated in the glial scar inhibit axon regeneration via their sulphated glycosaminoglycans (GAGs). Chondroitin 6-sulphotransferase-1 (C6ST-1) is upregulated after injury leading to an increase in 6-sulphated GAG. In this study, we ask if this increase in 6-sulphated GAG is responsible for the increased inhibition within the glial scar, or whether it represents a partial reversion to the permissive embryonic state dominated by 6-sulphated glycosaminoglycans (GAGs).

Stem cell therapy for glaucoma: possibilities and practicalities.

Glaucoma is a progressive, neurodegenerative, optic neuropathy in which currently available therapies cannot always prevent, and do not reverse, vision loss. Stem cell transplantation may provide a promising new avenue for treating many presently incurable degenerative conditions, including glaucoma. This article will explore the various ways in which transplantation of stem or progenitor cells may be applied for the treatment of glaucoma.

Concise review: toward stem cell-based therapies for retinal neurodegenerative diseases.

Loss of sight due to irreversible retinal neurodegeneration imposes a significant disease burden on both patients and society. Glaucoma and age-related macular degeneration are the commonest neurodegenerative blinding diseases in the developed world, and both are becoming increasingly prevalent as populations age. Our heavy reliance on our sense of sight means that visual loss often severely restricts day-to-day life, making it difficult to function without additional support.

The natural history of treated Parkinson's disease in an incident, community based cohort.

Background: Our understanding of the natural history of idiopathic Parkinson's disease (PD) remains limited. In the era of potential disease modifying therapies, there is an urgent need for studies assessing the natural evolution of treated PD from onset so that relevant outcome measures can be identified for clinical trials. No previous studies have charted progression in unselected patients followed from the point of diagnosis.

Sequential generation of olfactory bulb glutamatergic neurons by Neurog2-expressing precursor cells.

Background: While the diversity and spatio-temporal origin of olfactory bulb (OB) GABAergic interneurons has been studied in detail, much less is known about the subtypes of glutamatergic OB interneurons.

Results: We studied the temporal generation and diversity of Neurog2-positive precursor progeny using an inducible genetic fate mapping approach. We show that all subtypes of glutamatergic neurons derive from Neurog2 positive progenitors during development of the OB.

Glioblastoma cell lines derived under serum-free conditions can be used as an in vitro model system to evaluate therapeutic response.

We provide evidence that six glioblastoma cell lines derived and maintained under serum-free conditions secrete VEGF and four also expressed VEGF(R2). Expression of VEGF(R2) was associated with reduced proliferation in response to anti-VEGF antibodies. Spontaneous loss of VEGF(R2) over passage was associated with loss of this anti-proliferative effect.

LIF in the regulation of T-cell fate and as a potential therapeutic.

At the heart of lineage commitment within the adaptive immune response is the intrinsic genetic plasticity of the naive peripheral T lymphocyte (T cell). Primary activation by presentation of cognate antigen is coupled to rapid T-cell cycling and progressive epigenetic changes that guide the cell down distinct T-cell lineages, either effector (Th1, Th2, Th17) or tolerogenic (Treg). Fate choice is influenced both by strength of the priming activation signal and by cues from the micro-environment that are integrated with lineage-specific gene expression profiles, eventually becoming hard-wired in the fully differentiated cell.

Cell origin and culture history determine successful integration of neural precursor transplants into the dentate gyrus of the adult rat.

The success of transplants of neural tissue into the adult dentate gyrus in generating mature neurons is highly variable. Here we address the roles of the origin of the tissue and its pre-implantation preparation, and show that both are critical. We transplanted neonatal cultured or primary rat cells from either the ventral subventricular zone (vSVZ) or the dentate gyrus (DG) into the adult rat DG.

Use of an adult rat retinal explant model for screening of potential retinal ganglion cell neuroprotective therapies.

PURPOSE. To validate an established adult organotypic retinal explant culture system for use as an efficient medium-throughput screening tool to investigate novel retinal ganglion cell (RGC) neuroprotective therapies. METHODS.

Defining meaningful outcome measures in trials of disease-modifying therapies in Parkinson's disease.

Introduction: Although a range of treatments is available for Parkinson's disease (PD), conventional therapies merely improve the symptoms of the disorder and are not considered to have any effect on underlying neurodegeneration. Neuronal loss continues inexorably and leads to increasing handicap and disability as the disease advances. A fundamental goal of PD research has been to develop drugs that delay or halt progression - so-called disease-modifying therapies (DMTs).

Analysis of Schwann-astrocyte interactions using in vitro assays.

Schwann cells are one of the commonly used cells in repair strategies following spinal cord injuries. Schwann cells are capable of supporting axonal regeneration and sprouting by secreting growth factors (1,2) and providing growth promoting adhesion molecules (3) and extracellular matrix molecules (4). In addition they myelinate the demyelinated axons at the site of injury (5).

Parkinson's disease--the continuing search for biomarkers.

There is currently no well-established biomarker for Parkinson's disease. The need to better diagnose the condition, define the subtypes of disease, and follow its course independent of any symptomatic drug effects is well-established. In this review, we will begin by reviewing the evidence for biological fluid biomarkers in Parkinson's disease.

The factor structure of the UPDRS as an index of disease progression in Parkinson's disease.

The optimum method for evaluating disease progression in Parkinson's disease (PD) has not been established, and this has implications for clinical trials. The majority of previous studies have utilized change on the Unified Parkinson's disease Rating Scale (UPDRS) as an index of progression. However, the UPDRS has not been validated for this purpose.

Asymptomatic sleep abnormalities are a common early feature in patients with Huntington's disease.

Huntington's disease (HD) is a fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric disturbance. In this article, we used polysomnography, actigraphy and a variety of validated questionnaires to ascertain the extent to which sleep changes are identifiable and measurable in mild stage HD, and importantly, to see whether patients are negatively impacted by the changes in their sleep. We found significant differences in sleep architecture and sleep efficiency in patients compared with controls using polysomnography.

Human stem cell-derived neurons: a system to study human tau function and dysfunction.

Background: Intracellular filamentous deposits containing microtubule-associated protein tau constitute a defining characteristic of many neurodegenerative disorders. Current experimental models to study tau pathology in vitro do not usually recapitulate the tau expression pattern characteristic of adult human brain. In this study, we have investigated whether human embryonic stem cell-derived neurons could be a good model to study human tau distribution, function and dysfunction.

The roles of BDNF, pCREB and Wnt3a in the latent period preceding activation of progenitor cell mitosis in the adult dentate gyrus by fluoxetine.

The formation of new neurons continues into adult life in the dentate gyrus of the rat hippocampus, as in many other species. Neurogenesis itself turns out to be highly labile, and is regulated by a number of factors. One of these is the serotoninergic system: treatment with drugs (such as the SSRI fluoxetine) markedly stimulates mitosis in the progenitor cells of the dentate gyrus.

Identifying sleep disturbances in Huntington's disease using a simple disease-focused questionnaire.

Sleep disturbances have been shown to affect patients with various neurological diseases, including Huntington's disease (HD). We therefore aimed to develop a sleep questionnaire that could be used by clinicians to help identify sleep disturbances in patients with the disease.Design A detailed questionnaire was used that was modelled on recent sleep questionnaires used for Parkinson's disease patients, and developed after consultation with sleep specialists.

Human fetal neural precursor cells can up-regulate MHC class I and class II expression and elicit CD4 and CD8 T cell proliferation.

The use of allogeneic fetal neural precursor cells (NPCs) as a cell replacement therapy in neurodegenerative disorders holds great promise. However, previous studies concerning the possibility of alloimmune rejection of the transplanted cells have been inconclusive. Here, we used flow cytometry to quantify the expression of major histocompatibility complex (MHC) molecules by human NPCs, obtained from the cortex or ventral mesencephalon of fetuses with gestational ages between 7 and 11 weeks.

Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson's disease.

Cognitive impairment in patients with Parkinson's disease is gaining increased clinical significance owing to the relative success of therapeutic approaches to the motor symptoms of this disorder. Early investigations contributed to the concept of subcortical dementia associated with bradyphrenia and cognitive rigidity. For cognition in parkinsonian disorders, this notion developed into the concept of mild cognitive impairment and fronto-executive dysfunction in particular, driven mainly by dopaminergic dysmodulation and manifesting as deficits in flexibility, planning, working memory, and reinforcement learning.

Rab11 and its effector Rab coupling protein contribute to the trafficking of beta 1 integrins during axon growth in adult dorsal root ganglion neurons and PC12 cells.

Integrins play an important part in axon growth, but integrin traffic in neurons is poorly understood. Expression of the tenascin-C-binding integrin alpha9 promotes axon regeneration. We have therefore studied the mechanism by which alpha9 integrin and its partner beta1 are trafficked along axons and at the growth cone using adult DRG neurons and PC12 cells.

Effect of agomelatine and its interaction with the daily corticosterone rhythm on progenitor cell proliferation in the dentate gyrus of the adult rat.

Agomelatine, a novel melatonin analogue and anti-depressant that acts as an agonist on melatonin receptors 1 and 2 and as an antagonist at the 5HT2C receptor, was tested for its effects on cell proliferation in the dentate gyrus of the adult rat hippocampus under intact and flattened corticosterone rhythm conditions. Agomelatine stimulated mitosis rates in the intact male rat. Flattening the daily corticosterone rhythm by inserting a subcutaneous pellet of this steroid prevented the action of agomelatine.

Neuropeptide Y modifies the disease course in the R6/2 transgenic model of Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by progressive neuronal dysfunction and cell loss, especially striatal GABAergic neurons, generating motor, cognitive and affective problems. Although the disease-causing gene is known, the exact mechanism by which it induces its pathological effect remains unknown, and no cure is currently available for this disease. Interestingly, striatal neurons that express neuropeptide Y (NPY) are preferentially spared in HD and the number of such cells is increased in the striatum of HD patients.