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https://www.readbyqxmd.com/read/29656478/transplantation-of-neural-progenitor-cells-expressing-glial-cell-line-derived-neurotrophic-factor-into-the-motor-cortex-as-a-strategy-to-treat-amyotrophic-lateral-sclerosis
#1
Gretchen M Thomsen, Pablo Avalos, Annie A Ma, Mor Alkaslasi, Noell Cho, Livia Wyss, Jean-Philippe Vit, Marlesa Godoy, Patrick Suezaki, Oksana Shelest, Krystof S Bankiewicz, Clive N Svendsen
Early dysfunction of cortical motor neurons may underlie the initiation of amyotrophic lateral sclerosis (ALS). As such, the cortex represents a critical area of ALS research and a promising therapeutic target. In the current study, human cortical-derived neural progenitor cells engineered to secrete glial cell line-derived neurotrophic factor (GDNF) were transplanted into the SOD1G93A ALS rat cortex, where they migrated, matured into astrocytes, and released GDNF. This protected motor neurons, delayed disease pathology and extended survival of the animals...
April 15, 2018: Stem Cells
https://www.readbyqxmd.com/read/29656289/high-concentration-of-glial-cell-line-derived-neurotrophic-factor-protects-primary-astrocytes-from-apoptosis
#2
Yuqian Wang, Yuxia Qin, Tingwen Guo, Chuanxi Tang, Liyun Liu, Dianshuai Gao
BACKGROUND: Studies have shown that astrocytes play an important role in a variety of biological processes, so damage to astrocytes can cause a series of related diseases. Glial cell line-derived neurotrophic factor (GDNF) has always been considered a protective factor for dopamine neurons. However, it remains unclear whether GDNF has a protective effect on glial cells, especially astrocytes. In this study, we put forward the hypothesis that a high concentration of GDNF in the microenvironment of astrocytes exerts an inhibitory effect on the apoptosis of astrocytes by DNA-damaging reagents...
April 13, 2018: Developmental Neuroscience
https://www.readbyqxmd.com/read/29649627/overexpression-of-hipk2-attenuates-spinal-cord-injury-in-rats-by-modulating-apoptosis-oxidative-stress-and-inflammation
#3
Renbo Li, Jingbo Shang, Wei Zhou, Li Jiang, Donghui Xie, Guanjun Tu
HIPK2 is considered to be a tumor suppressor. It also has been implicated in several functions such as apoptosis and inflammation that are linked to spinal cord injury (SCI). However, whether HIPK2 ameliorates the neurological pain of SCI remains unclear. Here, we investigated the effects of HIPK2 on neurological function, oxidative stress, levels of inflammatory cytokines and expression of Bcl-2/Bax in an SCI model. Firstly, we evaluated the therapeutic effects of HIPK2 on neurological pain in the SCI rat using the Basso, Beattie and Bresnahan scores and H & E staining...
April 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29649411/the-in-vitro-differentiation-of-gdnf-gene-engineered-amniotic-fluid-derived-stem-cells-into-renal-tubular-epithelial-like-cells
#4
Ying Lu, Zhuojun Wang, Lu Chen, Jia Wang, Shulin Li, Caixia Liu, Dong Sun
Amniotic fluid is an alternative source of stem cells, and human amniotic fluid-derived stem cells (AFSCs) obtained from a small amount of amniotic fluid collected during the second trimester represent a novel source for use in regenerative medicine. These AFSCs are characterized by lower diversity, a higher proliferation rate and a wider differentiation capability than adult mesenchymal stem cells (MSCs). AFSCs are selected based on the cell surface marker c-kit receptor (CD117) using immunomagnetic sorting...
March 15, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29649409/the-forkhead-transcription-factor-foxc2-is-required-for-maintaining-murine-spermatogonial-stem-cells
#5
Chao Wei, Hao Lin, Sheng Cui
Continuous spermatogenesis from puberty to old age in males relies on spermatogonial stem cells (SSCs) that possess the property of self-renewal and differentiation. The delicate balance between self-renewal and differentiation is of great importance. In mice, SSCs exist as a subpopulation of undifferentiated spermatogonia. SSCs are controlled by intrinsic molecular pathways which can be activated by extrinsic signals. Our results here first show that the expression of forkhead box C2 (FOXC2) is restricted to GFRα1 positive spermatogonia in the testis...
March 13, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29621559/neurotrophins-and-cholinergic-enzyme-regulated-by-calpain-2-new-insights-into-neuronal-apoptosis-induced-by-polybrominated-diphenyl-ether-153
#6
Hongmei Zhang, Xiaorong Yang, Huajun Zhang, Xin Li, Zhihong Zhang, Lifang Hou, Zemin Wang, Qiao Niu, Tong Wang
Polybrominated diphenyl ether-153 (BDE-153) has been demonstrated to induce neuronal apoptosis in rat cerebral cortex and primary neurons. Neurotrophins and cholinergic enzymes play critical roles in the neuronal survival, maintenance, synaptic plasticity and learning memory, however, their roles in neuronal apoptosis following the BDE-153 treatment remain unclear. In this study, we firstly explored the possible predominant pathway underlying the neuronal apoptotic induced by the BDE-153 treatment in rat cerebral cortex, by measuring expression levels (protein and mRNA) of p53, caspase-3, 8, 9, calpain-1, and calpain-2, detected the expression levels (protein and mRNA) of neurotrophins including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), and measured acetylcholinesterase (AchE) and choline acetyltransferase (ChaT) activities in rat cerebral cortex and primary neurons following BDE-153 treatment with or without pretreatment with inhibitors...
April 2, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29617307/gfra1-a-novel-molecular-target-for-the-prevention-of-osteosarcoma-chemoresistance
#7
REVIEW
Mihwa Kim, Dae Joon Kim
The glycosylphosphatidylinositol-linked GDNF (glial cell derived neurotrophic factor) receptor alpha (GFRA), a coreceptor that recognizes the GDNF family of ligands, has a crucial role in the development and maintenance of the nervous system. Of the four identified GFRA isoforms, GFRA1 specifically recognizes GDNF and is involved in the regulation of proliferation, differentiation, and migration of neuronal cells. GFRA1 has also been implicated in cancer cell progression and metastasis. Recent findings show that GFRA1 can contribute to the development of chemoresistance in osteosarcoma...
April 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29615705/gdnf-expressing-macrophages-mitigate-loss-of-dopamine-neurons-and-improve-parkinsonian-symptoms-in-mitopark-mice
#8
Cang Chen, Xiuhua Li, Guo Ge, Jingwei Liu, K C Biju, Suzette D Laing, Yusheng Qian, Cori Ballard, Zhixu He, Eliezer Masliah, Robert A Clark, Jason C O'Connor, Senlin Li
Glial cell line-derived neurotrophic factor (GDNF) is the most potent neuroprotective agent tested in cellular and animal models of Parkinson's disease (PD). However, CNS delivery of GDNF is restricted by the blood-brain barrier (BBB). Using total body irradiation as transplant preconditioning, we previously reported that hematopoietic stem cell (HSC) transplantation (HSCT)-based macrophage-mediated gene therapy could deliver GDNF to the brain to prevent degeneration of nigrostriatal dopamine (DA) neurons in an acute murine neurotoxicity model...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29614078/a-bi-stable-feedback-loop-between-gdnf-egr1-and-er%C3%AE-contribute-to-endocrine-resistant-breast-cancer
#9
Sachi Horibata, Edward J Rice, Hui Zheng, Chinatsu Mukai, Tinyi Chu, Brooke A Marks, Scott A Coonrod, Charles G Danko
Discovering regulatory interactions between genes that specify the behavioral properties of cells remains an important challenge. We used the dynamics of transcriptional changes resolved by PRO-seq to identify a regulatory network responsible for endocrine resistance in breast cancer. We show that GDNF leads to endocrine resistance by switching the active state in a bi-stable feedback loop between GDNF, EGR1, and the master transcription factor ERα. GDNF stimulates MAP kinase, activating the transcription factors SRF and AP-1...
2018: PloS One
https://www.readbyqxmd.com/read/29608944/previous-early-life-stress-modifies-acute-corticosterone-induced-synaptic-plasticity-in-the-medial-prefrontal-cortex-of-adolescent-rats
#10
Iwona Majcher-Maślanka, Anna Solarz, Krzysztof Wędzony, Agnieszka Chocyk
Stress can either strengthen coping strategies or enhance the risk of depression and anxiety. Synaptic plasticity is one of the key brain functions that can be affected by stress. We have previously shown that early-life stress in the form of maternal separation (MS) impairs functional synaptic plasticity in the medial prefrontal cortex (mPFC), i.e., long-term potentiation (LTP), in adolescent rats. It has been postulated that a previous experience of prolonged stress can modify the response to a subsequent acute stress challenge and influence coping strategies...
March 30, 2018: Neuroscience
https://www.readbyqxmd.com/read/29608602/er-positive-breast-cancer-cells-are-poised-for-ret-mediated-endocrine-resistance
#11
Sachi Horibata, Edward J Rice, Chinatsu Mukai, Brooke A Marks, Kelly Sams, Hui Zheng, Lynne J Anguish, Scott A Coonrod, Charles G Danko
The RET tyrosine kinase signaling pathway is involved in the development of endocrine resistant ER+ breast cancer. However, we know little about how ER+ cells activate RET signaling and initiate an endocrine resistant phenotype. Here we show that both ER+ endocrine resistant and sensitive breast cancers have a functional RET tyrosine kinase signaling pathway, but that endocrine sensitive breast cancer cells lack RET ligands that are necessary to drive endocrine resistance. Transcription of one RET ligand, GDNF, is necessary and sufficient to confer resistance in the ER+ MCF-7 cell line...
2018: PloS One
https://www.readbyqxmd.com/read/29601828/identification-of-variants-in-ret-and-ihh-pathway-members-in-a-large-family-with-history-of-hirschsprung-disease
#12
Y Sribudiani, R K Chauhan, M M Alves, L Petrova, E Brosens, C Harrison, T Wabbersen, B M de Graaf, T Rügenbrink, G Burzynski, R W W Brouwer, W F J van IJcken, S M Maas, A de Klein, J Osinga, B J L Eggen, A J Burns, A S Brooks, I T Shepherd, R M W Hofstra
BACKGROUND & AIMS: Hirschsprung disease (HSCR) is an inherited congenital disorder characterized by absence of enteric ganglia in the distal part of the gut. Variants in ret proto-oncogene (RET) have been associated with up to 50% of familial and 35% of sporadic cases. We searched for variants that affect disease risk in a large, multi-generational family with history of HSCR in a linkage region previously associated with the disease (4q31.3-q32.3) and exome wide. METHODS: We performed exome sequencing analyses of a family in the Netherlands with 5 members diagnosed with HSCR and 2 members diagnosed with functional constipation...
March 27, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29592535/commentary-on-some-recent-theses-relevant-to-combating-aging-april-2018
#13
Benjamin Zealley, Aubrey D N J de Grey
Theses reviewed in this issue include "An Intranasal GDNF Gene Therapy Approach for Treating Parkinson's Disease", "Controlling Depth of Cellular Quiescence By an Rb-E2F Network Switch", "Immunoregulation of the Central Response to Peripheral Nerve Injury: Motoneuron Survival and Relevance to ALS", and "Single-Cell Whole-Genome Sequencing Reveals Widespread Somatic Copy Number Variations in the Developing Cerebral Cortex".
March 28, 2018: Rejuvenation Research
https://www.readbyqxmd.com/read/29588162/aminochrome-decreases-ngf-gdnf-and-induces-neuroinflammation-in-organotypic-midbrain-slice-cultures
#14
Fillipe M de Araújo, Rafael S Ferreira, Cleide S Souza, Cleonice Creusa Dos Santos, Tácio L R S Rodrigues, Juliana Helena C E Silva, Juciano Gasparotto, Daniel Pens Gelain, Ramon S El-Bachá, Maria de Fátima D Costa, José Claudio M Fonseca, Juan Segura-Aguilar, Silvia L Costa, Victor Diogenes A Silva
Recent evidence shows that aminochrome induces glial activation related to neuroinflammation. This dopamine derived molecule induces formation and stabilization of alpha-synuclein oligomers, mitochondria dysfunction, oxidative stress, dysfunction of proteasomal and lysosomal systems, endoplasmic reticulum stress and disruption of the microtubule network, but until now there has been no evidence of effects on production of cytokines and neurotrophic factors, that are mechanisms involved in neuronal loss in Parkinson's disease (PD)...
March 24, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29580890/mifepristone-attenuates-depression-like-changes-induced-by-chronic-central-administration-of-interleukin-1%C3%AE-in-rats
#15
Yong-Ping Zhang, Hao-Yin Wang, Cai Zhang, Bai-Ping Liu, Zhi-Lan Peng, Yu-Yu Li, Cai Song
Increased proinflammatory cytokines, such as interleukin (IL)-1β, may play an important role in the etiology of depression because they cause the hypothalamic-pituitary-adrenal axis to release glucocorticoids (GC) and induce dysfunction of serotonin and norepinephrine neurotransmission. Sustained increase in GC may activate microglia to induce neuroinflammation, and suppress astrocytes to produce neurotrophins, which lead to neuronal apoptosis. Here, we tested the hypothesis that glucocorticoid receptor (GR) antagonist mifepristone (RU486) may attenuate IL-1β-induced depression-like behavior by regulating the neuroinflammation and neurotrophin functions of microglia and astrocytes...
March 23, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29573696/low-omega-6-omega-3-ratio-in-a-maternal-protein-deficient-diet-promotes-histone-3-changes-in-progeny-neural-cells-and-favors-leukemia-inhibitory-factor-gene-transcription
#16
Alinny Rosendo Isaac, Emerson Alexandre Neves da Silva, Rhowena Jane Barbosa de Matos, Ricielle Lopes Augusto, Giselle Machado Magalhães Moreno, Ingrid Prata Mendonça, Raphael Fabrício de Souza, Paulo Euzébio Cabral-Filho, Cláudio Gabriel Rodrigues, Catarina Gonçalves-Pimentel, Fabíola Lacerda, Maria Luisa Martins Alessio, Marcelo Cairrão Araujo Rodrigues, Belmira Lara da Silveira Andrade-da-Costa
Omega-3 (n-3) fatty acids modulate epigenetic changes critical to genesis and differentiation of neural cells. Conversely, maternal protein-malnutrition can negatively modify these changes. This study investigated whether a low n-6/n-3 ratio in a maternal diet could favor histone-3 (H3) modifications, gene transcription and differentiation in the offspring neural cells even under protein-deficiency. Female rats fed a control (Ct), or 3 types of multideficient diets differing in protein levels or linoleic/alpha-linolenic fatty acid ratios (RBD, RBD-C, RBD-SO) from 30 days prior to mating and during pregnancy...
February 13, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29564810/kir6-2-deficiency-promotes-mesencephalic-neural-precursor-cell-differentiation-via-regulating-mir-133b-gdnf-in-a-parkinson-s-disease-mouse-model
#17
Yan Zhou, Jialei Zhu, Yang Lv, Chenghuan Song, Jianhua Ding, Ming Xiao, Ming Lu, Gang Hu
The loss of dopaminergic (DA) neurons in the substantia nigra (SN) is a major feature in the pathology of Parkinson's disease (PD). Using neural stem or progenitor cells (NSC/NPCs), the prospect of replacing the missing or damaged DA neurons is very attractive for PD therapy. However, little is known about the endogenous mechanisms and molecular pathways regulating the NSC/NPC proliferation and differentiation in the development of PD. Herein, using Kir6.2 knockout (Kir6.2-/- ) mice, we observed that genetic deficiency of Kir6...
March 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29562865/regulatable-lentiviral-hematopoietic-stem-cell-gene-therapy-in-a-mouse-model-of-parkinson-s-disease
#18
Guo Ge, Cang Chen, Michael James Guderyon, Jingwei Liu, Zhixu He, Yanni Yu, Robert A Clark, Senlin Li
Glial cell line-derived neurotrophic factor (GDNF) exhibits potent neuroprotective properties in preclinical models of Parkinson's disease (PD), but challenges in GDNF delivery have been reported from clinical trials. To address this barrier, we developed a hematopoietic stem cell transplantation (HSCT) -based macrophage-mediated GDNF therapy platform. Here we introduced a regulatable lentiviral vector (LV-MSP-Tet-Off-hGDNF) in order to allow the expression of human GDNF to be adjusted or stopped by oral administration of doxycycline (Dox)...
March 21, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29560767/protective-effect-of-compound-danshen-salvia-miltiorrhiza-dripping-pills-alone-and-in-combination-with-carbamazepine-on-kainic-acid-induced-temporal-lobe-epilepsy-and-cognitive-impairment-in-rats
#19
Chen Jia, Shanshan Han, Liming Wei, Xiangji Dang, Qianqian Niu, Mengyu Chen, Boqun Cao, Yuting Liu, Haisheng Jiao
CONTEXT: Temporal lobe epilepsy (TLE) is resistant to antiepileptic drugs (AEDs) and is associated with cognitive impairment. The modern Chinese medicine, compound Danshen dripping pills (CDDP), is clinically effective in treating epilepsy and improving cognitive impairment. OBJECTIVE: This study evaluated the protective effects of CDDP alone and in combination with carbamazepine (CBZ) on kainic acid-induced TLE and cognitive impairment in rats. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into five groups: control (sham operated), model, CDDP, CBZ and combined...
December 2018: Pharmaceutical Biology
https://www.readbyqxmd.com/read/29556564/the-role-of-the-shcd-and-ret-interaction-in-neuroblastoma-survival-and-migration
#20
Zeanap A Mabruk, Samrein B M Ahmed, Asha Caroline Thomas, Sally A Prigent
Preliminary screening data showed that the ShcD adaptor protein associates with the proto-oncogene RET receptor tyrosine kinase. In the present study, we aimed to investigate the molecular interaction between ShcD and RET in human neuroblastoma cells and study the functional impact of this interaction. We were able to show that ShcD immunoprecipitated with RET from SK-N-AS neuroblastoma cell lysates upon GDNF treatment. This result was validated by ShcD-RET co-localization, which was visualized using a fluorescence microscope...
March 2018: Biochemistry and Biophysics Reports
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