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https://www.readbyqxmd.com/read/28821675/synergistic-toxicity-of-polyglutamine-expanded-tbp-in-glia-and-neuronal-cells-therapeutic-implications-for-sca17
#1
Yang Yang, Su Yang, Jifeng Guo, Yiting Cui, Baisha Tang, Xiao-Jiang Li, Shihua Li
Spinocerebellar ataxia 17 (SCA17) is caused by polyglutamine (polyQ) repeat expansion in the TATA-binding protein (TBP) and is among a family of neurodegenerative diseases in which polyQ expansion leads to preferential neuronal loss in the brain. Although previous studies have demonstrated that expression of polyQ-expanded proteins in glial cells can cause neuronal injury via non-cell-autonomous mechanisms, these studies investigated animal models that overexpress transgenic mutant proteins. Since glial cells are particularly reactive to overexpressed mutant proteins, it is important to investigate the in vivo role of glial dysfunction in neurodegeneration when mutant polyQ proteins are endogenously expressed...
August 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28818672/glutathione-monoethyl-ester-prevents-tdp-43-pathology-in-motor-neuronal-nsc-34%C3%A2-cells
#2
Tong Chen, Bradley J Turner, Philip M Beart, Lucy Sheehan-Hennessy, Chinasom Elekwachi, Hakan Muyderman
Oxidative stress is recognised as central in a range of neurological diseases including Amyotrophic lateral sclerosis (ALS), a disease characterised by fast progressing death of motor neurons in the brain and spinal cord. Cellular pathology includes cytosolic protein aggregates in motor neurons and glia of which potentially cytotoxic hyper-phosphorylated fragments of the Transactive response DNA Binding Protein 43 kDa (TDP-43) constitute a major component. This is closely associated with an additional loss of nuclear TDP-43 expression indicating a "loss of function" mechanism, accelerating motor neuron (MN) loss...
August 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28817799/human-astrocyte-maturation-captured-in-3d-cerebral-cortical-spheroids-derived-from-pluripotent-stem-cells
#3
Steven A Sloan, Spyros Darmanis, Nina Huber, Themasap A Khan, Fikri Birey, Christine Caneda, Richard Reimer, Stephen R Quake, Ben A Barres, Sergiu P Paşca
There is significant need to develop physiologically relevant models for investigating human astrocytes in health and disease. Here, we present an approach for generating astrocyte lineage cells in a three-dimensional (3D) cytoarchitecture using human cerebral cortical spheroids (hCSs) derived from pluripotent stem cells. We acutely purified astrocyte-lineage cells from hCSs at varying stages up to 20 months in vitro using immunopanning and cell sorting and performed high-depth bulk and single-cell RNA sequencing to directly compare them to purified primary human brain cells...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28814778/in-vivo-and-in-vitro-sex-differences-in-the-dendritic-morphology-of-developing-murine-hippocampal-and-cortical-neurons
#4
Kimberly P Keil, Sunjay Sethi, Machelle D Wilson, Hao Chen, Pamela J Lein
Altered dendritic morphology is common in neurodevelopmental disorders (NDDs), many of which show sex biases in prevalence, onset and/or severity. However, whether dendritic morphology varies as a function of sex in juvenile mice or primary neuronal cell cultures is largely unknown even though both are widely used models for studying NDDs. To address this gap, we quantified dendritic morphology in CA1 pyramidal hippocampal and adjacent somatosensory pyramidal cortical neurons from male and female postnatal day (P)28 C57BL/6J mice...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814327/neocortical-sox9-radial-glia-generate-glutamatergic-neurons-for-all-layers-but-lack-discernible-evidence-of-early-laminar-fate-restriction
#5
E S Kaplan, K A Ramos-Laguna, A B Mihalas, R A M Daza, R F Hevner
Glutamatergic neurons in the cerebral cortex are derived from embryonic neural stem cells known as radial glial progenitors (RGPs). Early RGPs, present at the onset of cortical neurogenesis, are classically thought to produce columnar clones of glutamatergic neurons spanning the cortical layers. Recently, however, it has been reported that a subset of early RGPs may undergo early commitment to upper layer neuron fates, thus bypassing genesis of deep layer neurons. However, the latter mode of early RGP differentiation was not confirmed in some other studies, and remains controversial...
August 16, 2017: Neural Development
https://www.readbyqxmd.com/read/28807933/mice-deficient-in-lysophosphatidic-acid-acyltransferase-%C3%AE-lpaat%C3%AE-acylglycerophosphate-acyltransferase-4-agpat4-have-impairments-in-spatial-learning-and-memory-associated-with-reductions-in-nmda-and-ampa-receptors
#6
Ryan M Bradley, Emily B Mardian, Darin Bloemberg, Juan J Aristizabal Henao, Andrew S Mitchell, Phillip M Marvyn, Katherine A Moes, Ken D Stark, Joe Quadrilatero, Robin E Duncan
We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here we report that Lpaatδ (-/-) mice display impaired spatial learning and memory compared to wildtype littermates in the Morris Water Maze, and investigated potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged...
August 14, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28806173/the-%C3%AE-alanine-transporter-balat-is-required-for-visual-neurotransmission-in-drosophila
#7
Yongchao Han, Liangyao Xiong, Ying Xu, Tian Tian, Tao Wang
The recycling of neurotransmitters is essential for sustained synaptic transmission. In Drosophila, histamine recycling is required for visual synaptic transmission. Synaptic histamine is rapidly taken up by laminar glia, and is converted to carcinine. After delivered back to photoreceptors, carcinine is hydrolyzed to release histamine and β-alanine. This histamine is repackaged into synaptic vesicles, but it is unclear how the β-alanine is returned to the laminar glial cells. Here, we identified a new β-alanine transporter, which we named BalaT (Beta-alanine Transporter)...
August 14, 2017: ELife
https://www.readbyqxmd.com/read/28804608/remyelination-improvement-after-neurotrophic-factors-secreting-cells-transplantation-in-rat-spinal-cord-injury
#8
Shahnaz Razavi, Nazem Ghasemi, Mohammad Mardani, Hossein Salehi
OBJECTIVES: Neurotrophic factors secreting cells (NTS-SCs) may be a superior cell source for cell-based therapy in neurodegenerative diseases. NTS-SCs are able to secrete some neurotrophic Such as nerve growth factor and glia-derived neurotrophic factor. Our primary aim was to assess transplantation of neurotrophic factor secreting cells derived from human adipose-derived stem cells (hADSCs) into the damaged spinal cord rats and determine the potential of these cells in remyelination...
April 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28804448/erythropoietin-protects-against-lipopolysaccharide-induced-microgliosis-and-abnormal-granule-cell-development-in-the-ovine-fetal-cerebellum
#9
Annie R A McDougall, Nadia Hale, Sandra Rees, Richard Harding, Robert De Matteo, Stuart B Hooper, Mary Tolcos
Erythropoietin (EPO) ameliorates inflammation-induced injury in cerebral white matter (WM). However, effects of inflammation on the cerebellum and neuroprotective effects of EPO are unknown. Our aims were to determine: (i) whether lipopolysaccharide (LPS)-induced intrauterine inflammation causes injury to, and/or impairs development of the cerebellum; and (ii) whether recombinant human EPO (rhEPO) mitigates these changes. At 107 ± 1 days gestational age (DGA; ~0.7 of term), fetal sheep received LPS (~0.9 μg/kg; i...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28803967/igdb-2-an-ig-fniii-protein-binds-the-ion-channel-lgc-34-and-controls-sensory-compartment-morphogenesis-in-c-elegans
#10
Wendy Wang, Elliot A Perens, Grigorios Oikonomou, Yun Lu, Shai Shaham
Sensory organ glia surround neuronal receptive endings (NREs), forming a specialized compartment important for neuronal activity, and reminiscent of glia-ensheathed synapses in the central nervous system. We previously showed that DAF-6, a Patched-related protein, is required in glia of the C. elegans amphid sensory organ to restrict sensory compartment size. LIT-1, a Nemo-like kinase, and SNX-1, a retromer component, antagonize DAF-6 and promote compartment expansion. To further explore the machinery underlying compartment size control, we sought genes whose inactivation restores normal compartment size to daf-6 mutants...
August 10, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28801522/vascular-niche-contribution-to-age-associated-neural-stem-cell-dysfunction
#11
Deana Marie Apple, Erzsebet Kokovay
Neural stem cells (NSCs) persist throughout life in the dentate gyrus and the ventricular-subventricular zone (V-SVZ), where they continuously provide new neurons and some glia. These cells are found in specialized niches that regulate quiescence, activation, differentiation, and cell fate choice. A key aspect of the regulatory niche is the vascular plexus, which modulates NSC behavior during tissue homeostasis and regeneration. During aging, NSCs become depleted and dysfunctional, resulting in reduced neurogenesis and poor brain repair...
August 11, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28798665/maternal-diabetes-alters-expression-of-micrornas-that-regulate-genes-critical-for-neural-tube-development
#12
Seshadri Ramya, Sukanya Shyamasundar, Boon Huat Bay, S Thameem Dheen
Maternal diabetes is known to cause neural tube defects (NTDs) in embryos and neuropsychological deficits in infants. Several metabolic pathways and a plethora of genes have been identified to be deregulated in developing brain of embryos by maternal diabetes, although the exact mechanism remains unknown. Recently, miRNAs have been shown to regulate genes involved in brain development and maturation. Therefore, we hypothesized that maternal diabetes alters the expression of miRNAs that regulate genes involved in biological pathways critical for neural tube development and closure during embryogenesis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28798420/hiv-1-tat-induced-diarrhea-evokes-an-enteric-glia-dependent-neuroinflammatory-response-in-the-central-nervous-system
#13
Giuseppe Esposito, Elena Capoccia, Stefano Gigli, Marcella Pesce, Eugenia Bruzzese, Alessandra D'Alessandro, Carla Cirillo, Alessandro di Cerbo, Rosario Cuomo, Luisa Seguella, Luca Steardo, Giovanni Sarnelli
Despite the effectiveness of combined anti-retroviral therapy, human immunodeficiency virus (HIV) infected-patients frequently report diarrhea and neuropsychological deficits. It is claimed that the viral HIV-1 Trans activating factor (HIV-1 Tat) protein is responsible for both diarrhea and neurotoxic effects, but the underlying mechanisms are not known. We hypothesize that colonic application of HIV-1 Tat activates glial cells of the enteric nervous system (EGCs), leading to a neuroinflammatory response able to propagate to the central nervous system...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28795438/a-specific-gabaergic-synapse-onto-oligodendrocyte-precursors-does-not-regulate-cortical-oligodendrogenesis
#14
Maddalena Balia, Najate Benamer, María Cecilia Angulo
In the brain, neurons establish bona fide synapses onto oligodendrocyte precursor cells (OPCs), but the function of these neuron-glia synapses remains unresolved. A leading hypothesis suggests that these synapses regulate OPC proliferation and differentiation. However, a causal link between synaptic activity and OPC cellular dynamics is still missing. In the developing somatosensory cortex, OPCs receive a major type of synapse from GABAergic interneurons that is mediated by postsynaptic γ2-containing GABAA receptors...
August 10, 2017: Glia
https://www.readbyqxmd.com/read/28795331/cells-expressing-prominin-1-in-neonatal-murine-inferior-colliculus-differentiate-into-neurons-and-glia
#15
Haruka Okazaki, Akira Kanda, Seiji Kanda, Takaki Shimono, Yasutaka Yun, Yoshiki Kobayashi, Zeyun Wang, Hisashi Ooka, Kensuke Suzuki, Dan Bui Van, Koichi Tomoda, Hiroshi Iwai, Toshimasa Nishiyama
Inferior colliculus (IC) is a major center for the integration and processing of acoustic information from ascending auditory pathways. Damage to the IC as well as normal aging can impair auditory function. Novel strategies such as stem cell (SC)-based regenerative therapy are required for functional recovery because mature neural cells have a minimal regenerative capacity after an injury. However, it is not known if there are neural stem cells (NSCs) in the IC. Herein, we screened for NSCs by surface marker analysis using flow cytometry...
August 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28795287/recent-advances-in-the-classification-and-treatment-of-ependymomas
#16
REVIEW
Heather Leeper, Michelle M Felicella, Tobias Walbert
Ependymomas are a subgroup of ependymal glia-derived neoplasms that affect children as well as adults. Arising within any CNS compartment, symptoms at presentation can range from acute onset due to increased intracranial pressure to insidious myelopathy. The overall survival (OS) outcomes in adult patients across the subgroups is heterogeneous with subependymoma having an excellent prognosis often even in the absence of any treatment, whereas supratentorial ependymomas tend to be higher grade in nature and may have an OS of 5 years despite gross total resection and adjuvant radiation...
August 10, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28791751/the-gene-network-underlying-the-glial-regenerative-response-to-central-nervous-system-injury
#17
REVIEW
Kentaro Kato, Maria Losada-Perez, Alicia Hidalgo
Although the central nervous system does not regenerate, injury induces repair and regenerative responses in glial cells. In mammals, activated microglia clear up apoptotic cells and debris resulting from the injury, astrocytes form a scar that contains the lesion, and NG2-glia elicit a prominent regenerative response. NG2-glia regenerate themselves and differentiate into oligodendrocytes, which remyelinate axons leading to some recovery of locomotion. The regenerative response of glial cells is evolutionarily conserved across the animals and Drosophila genetics revealed an underlying gene network...
August 9, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28790893/brain-and-peripheral-atypical-inflammatory-mediators-potentiate-neuroinflammation-and-neurodegeneration
#18
REVIEW
Duraisamy Kempuraj, Ramasamy Thangavel, Govindhasamy P Selvakumar, Smita Zaheer, Mohammad E Ahmed, Sudhanshu P Raikwar, Haris Zahoor, Daniyal Saeed, Prashant A Natteru, Shankar Iyer, Asgar Zaheer
Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28777939/do-not-adjust-your-mind-the-fault-is-in-your-glia
#19
Robin J M Franklin, Edward T Bullmore
Glia have been implicated in schizophrenia, although whether they play a primary role is uncertain. In this issue of Cell Stem Cell, Windrem et al. (2017) transplant human glial progenitors from schizophrenia patients into mouse brains, which develop abnormalities and behaviors characteristic of schizophrenia, thereby suggesting a primary role for glia in the complex disease pathogenesis.
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28777795/regulation-of-gli-ciliary-localization-and-hedgehog-signaling-by-the-py-nls-karyopherin-%C3%AE-2-nuclear-import-system
#20
Yuhong Han, Yue Xiong, Xuanming Shi, Jiang Wu, Yun Zhao, Jin Jiang
Hedgehog (Hh) signaling in vertebrates depends on primary cilia. Upon stimulation, Hh pathway components, including Gli transcription factors, accumulate at primary cilia to transduce the Hh signal, but the mechanisms underlying their ciliary targeting remains largely unknown. Here, we show that the PY-type nuclear localization signal (PY-NLS)/karyopherinβ2 (Kapβ2) nuclear import system regulates Gli ciliary localization and Hh pathway activation. Mutating the PY-NLS in Gli or knockdown of Kapβ2 diminished Gli ciliary localization...
August 2017: PLoS Biology
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