Roscovitine, an experimental CDK5 inhibitor, causes delayed suppression of microglial, but not astroglial recruitment around intracerebral dopaminergic grafts.

Roscovitine, an experimental CDK5 inhibitor, causes delayed suppression of microglial, but not astroglial recruitment around intracerebral dopaminergic grafts. Exp Neurol. 2019 Apr 24;: Authors: Tomov N, Surchev L, Wiedenmann C, Döbrössy M, Nikkhah G Abstract Inhibitors of cell cycle proteins are known to reduce glial activation and to be neuroprotective in a number of settings. In the context of intracerebral grafting, glial activation is documented to correlate with graft rejection. However, the effects of modification of glial reactivity following grafting in the CNS are poorly understood. Moreover, it is not completely clear if the glial cells themselves trigger the rejection process, or are they secondarily activated. The present study investigated the effect of microglial inhibition by the cyclin-dependant kinase 5 (CDK5) inhibitor roscovitine following intracerebral transplantation in the rodent model of Parkinson's disease. Single cell suspension of rat E14 ventral mesencephalic tissue was transplanted to the dopamine-depleted striatum of unilaterally 6-hydroxydopamine (6-OHDA) lesioned male Sprague-Dawley rats. Experimental animals received injections of roscovitine (20 mg/kg) or a vehicle solution three times following the procedure. Immunohistochemistry was carried out on Day 7 and Day 28 to quantitatively describe the glial reaction adjacent to grafts. The data confirm that systemic roscovitine treatment significantly reduced micr...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

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In this study, researchers studied 438,952 participants in the UK Biobank, who had a total of 24,980 major coronary events - defined as the first occurrence of non-fatal heart attack, ischaemic stroke, or death due to coronary heart disease. They used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to randomly divide the participants into groups, mimicking the effects of running a clinical trial. People with genes associated with lower blood pressure, lower LDL cholesterol, and a combination of both were put into different groups, and compared against those without thes...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Since the discovery of induced pluripotency more than a decade ago, researchers have been working towards the use of this technology to produce cells for use in tissue engineering and regenerative therapies. Induced pluripotent stem cells are functionally equivalent to embryonic stem cells; given suitable recipes and methods for the surrounding environment and signals, they can be made to generate any of the cell types in the body. The cornea of the eye is a comparatively simple starting point for tissue engineering, easier to work with in many ways, in generating tissues and in delivering cells to the patient. Here, the f...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Human NPCs can degrade α-syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures. Neurobiol Dis. 2019 Sep 05;:104609 Authors: Grudina C, Kouroupi G, Nonaka T, Hasegawa M, Matsas R, Zurzolo C Abstract Parkinson's disease (PD) is the second most common neurodegenerative disorder whereby loss of midbrain dopaminergic neurons results in motor dysfunction. Transplantation of human induced pluripotent stem cells (iPSCs) into the brain of patients affected by PD is one of the therapeutic approaches that has gained interest to compensate for t...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
Contributors : Tadashi Sunohara ; Asuka MorizaneSeries Type : Non-coding RNA profiling by arrayOrganism :Cell-based therapy is a promising treatment for neurodegenerative diseases such as Parkinson ’s disease or cardiac disease. Similarly, reconstruction of the corticospinal tract by cell transplantation is expected as a treatment for stroke and degenerative disease. For efficient cell integration to the corticospinal tract after transplantation, the induction or selection of corticofugal projection neuron (CFuPN) is important. However, no CFuPN specific surface markers for the purification are known. Recently, miRN...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by array Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Many studies, using pre-clinical models of SCI, have demonstrated the efficacy of chondroitinase ABC as a treatment for spinal cord injury and this has been confirmed in laboratories worldwide and in several animal models. The aim of this review is report the current state of research in the field and to compare the relative efficacies of these new interventions to improve outcomes in both acute and chronic models of SCI. We also report new methods of chondroitinase delivery and the outcomes of two clinical trials using the enzyme to treat spinal cord injury in dogs and disc herniation in human patients. ...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Dutta SK, Verma S, Jain V, Surapaneni BK, Vinayek R, Phillips L, Nair PP Abstract The role of the microbiome in health and human disease has emerged at the forefront of medicine in the 21st century. Over the last 2 decades evidence has emerged to suggest that inflammation-derived oxidative damage and cytokine induced toxicity may play a significant role in the neuronal damage associated with Parkinson's disease (PD). Presence of pro-inflammatory cytokines and T cell infiltration has been observed in the brain parenchyma of patients with PD. Furthermore, evidence for inflammatory changes has been reported i...
Source: Journal of Neurogastroenterology and Motility - Category: Gastroenterology Tags: J Neurogastroenterol Motil Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, we show here that sEVs are responsible for mediating paracrine senescence and speculate that they could be involved in inducing bystander senescence during therapy-induced senescence or aging. In fact, when compared to soluble factors, sEVs have different biophysical and biochemical properties as they have a longer lifespan than do soluble factors and they are more resistant to protease degradation. The idea that blocking sEV secretion could be a potential therapeutic approach to alleviate senescence "spreading" during chemotherapy-induced senescence or in aging tissues presents itself as a very at...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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