PDE9 inhibition promotes proliferation of neural stem cells via cGMP-PKG pathway following oxygen-glucose deprivation/reoxygenation injury in vitro

Publication date: Available online 9 December 2019Source: Neurochemistry InternationalAuthor(s): Xiao Huan, Cheng Oumei, Qiu Hongmei, Yang Junxia, Ma Xiaojiao, Jiang QingsongAbstractCerebral ischemia is one of leading causes of death and long-term disability worldwide. Stem cell-based therapy is promising some valuable strategies for the structural and functional recovery after ischemic insult. The inhibition of phosphodiesterases (PDEs) has wide spectrum neuroprotective properties by stimulating proliferation of neural stem cells (NSCs). However, the potential role of PDE9 on NSCs proliferation after cerebral ischemia is not well investigated. The present study aimed to assess the contribution of PDE9 inhibition on the proliferation of NSCs and to determine the details of its underlying mechanisms against cerebral ischemia. The survival and proliferation of NSCs were assessed by CCK-8 assay and BrdU immunofluorescence staining, respectively. PDE9 activity and cGMP level were measured by ELISA kits. The protein expression of PKG and BDNF was detected by Western blot. Exposing NSCs of cultured primary hippocampus to oxygen-glucose deprivation/reoxygenation (OGD/R) significantly decreased the survival rate, but increased the proliferation of NSCs. Meanwhile, PDE9 activity was decreased, cGMP level was increased, PKG and BDNF protein expression was increased. PF-04447953, a PDE9 inhibitor, increased the survival rate of NSCs, moreover, PDE9 activity reduced more, and NSCs prolif...
Source: Neurochemistry International - Category: Neuroscience Source Type: research

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Contributors : Jan T Czerminski ; Jeanne B LawrenceSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAlthough Down Syndrome (DS) is the leading genetic cause of intellectual disability in children, the developmental pathogenesis remains largely unknown, and better strategies are needed to investigate this. We previously showed that one copy of chromosome 21 can be epigenetically silenced in DS iPSCs by insertion of an XIST transgene, which produces a non-coding RNA that normally silences one X chromosome in female cells. XIST was shown to induce heterochromatin and silence transcription...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Contributors : Jan T Czerminski ; Jeanne B LawrenceSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAlthough Down Syndrome (DS) is the leading genetic cause of intellectual disability in children, the developmental pathogenesis remains largely unknown, and better strategies are needed to investigate this. We previously showed that one copy of chromosome 21 can be epigenetically silenced in DS iPSCs by insertion of an XIST transgene, which produces a non-coding RNA that normally silences one X chromosome in female cells. XIST was shown to induce heterochromatin and silence transcription...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
The J.P. Morgan Healthcare conference runs every year in San Francisco, a big draw for the biotech industry, and many organizations take the opportunity to host events at the same time. Among these, the SENS Research Foundation has for the past few years hosted a pitch day in which biotech companies in the longevity industry, largely startups, present to that portion of the Bay Area investor community interested in funding the treatment of aging as a medical condition. I was there to present on progress at Repair Biotechnologies, and took some notes on the other companies as they talked about their work. Kimera Labs ...
Source: Fight Aging! - Category: Research Authors: Tags: Investment Source Type: blogs
This study provides strong evidence that following a healthy lifestyle can substantially extend the years a person lives disease-free." Commentary on Recent Evidence for Cognitive Decline to Precede Amyloid Aggregation in Alzheimer's Disease https://www.fightaging.org/archives/2020/01/commentary-on-recent-evidence-for-cognitive-decline-to-precede-amyloid-aggregation-in-alzheimers-disease/ I can't say that I think the data presented in the research noted here merits quite the degree of the attention that it has been given in the popular science press. It is interesting, but not compelling if its role...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Polyglutamine tract-binding protein 1 (PQBP1), an intellectual disability causative gene, is involved in transcriptional and post-transcriptional regulation of gene expression in animals, and possibly also in plants. In our previous work, reduced brain size, associated with an elongated cell cycle duration in neural stem cells (NSCs), was observed in the NSCs conditional Pqbp1 gene knockout (cKO) mice, which mimic microcephaly patients. However, the physiological significance of PQBP1 in bone metabolism has not been elucidated. Here, we analyzed the bone phenotype of nestin-Cre Pqbp1-cKO mice. Surprisingl...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
This article is protected by copyright. All rights reserved. PMID: 31930687 [PubMed - as supplied by publisher]
Source: Anatomical Record - Category: Anatomy Authors: Tags: Anat Rec (Hoboken) Source Type: research
Publication date: Available online 30 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Mimi Zumwalt, Arubala P. ReddyAbstractA myriad of musculoskeletal conditions afflicts a vast number of the world's population from birth to death. Countless pathological diseases and traumatic injuries (acute and chronic) contribute to different human disabilities, causing a tremendous financial toll on the economy of healthcare. The medical field is continually searching for novel ways to combat orthopedically related conditions. The immediate goal is the restoration of anatomy then ultimat...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
Clinical trial of Autologous Hematopoietic Stem Cell Transplantation versus Best Available Therapy for Multiple Sclerosis (BEAT-MS) begins enrollment
Source: Disabled World - Category: Disability Tags: Clinical Trials Source Type: news
Leading ophthalmologists call on the new government to develop a national plan to fight blindness and address the critical lack of fundingAs leading ophthalmologists and researchers we are joining the eye research charity Fight for Sight to call for urgent action on blindness in 2020 to address the research funding gap.We know that serious sight loss doesn ’t discriminate – it can affect anyone at any time and it is on the increase. Science can already do so much and with the advent of new gene therapies and stem cell treatments we are so close to outcomes that were not possible a decade ago. Yet so much more n...
Source: Guardian Unlimited Science - Category: Science Authors: Tags: Blindness and visual impairment Medical research Disability Health Society Science Conservatives Source Type: news
ConclusionMEK-ERK and MNK-eIF4E pathways regulate protein translation, and our results suggest that aberrant translation distinct in TSC1/2-deficient NPCs could play a role in neurodevelopmental defects. Our data showing upregulation of these signaling pathways by rapamycin support a strategy to combine a MEK or a MNK inhibitor with rapamycin that may be superior for TSC-associated CNS defects. Importantly, our generation of isogenic sets of NPCs from TSC patients provides a valuable platform for translatome and large-scale drug screening studies. Overall, our studies further support the notion that early developmental eve...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
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