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https://www.readbyqxmd.com/read/28776278/expression-of-thyroid-stimulating-hormone-receptors-and-thyroglobulin-in-limbic-regions-in-the-adult-human-brain
#1
Meleshni Naicker, Strinivasen Naidoo
Expression of the human thyroid-specific proteins, thyroid-stimulating hormone receptor (TSH-R) and thyroglobulin (TG) in non-thyroid tissue is well-documented. TSH-R has been identified in the heart, kidney, bone, pituitary, adipose tissue, skin and astrocyte cultures. TG has been identified in the skin, thymus and kidney. However, none of those previous studies had identified TSH-R or TG in specific human brain regions. Previously, a pilot study conducted by our group on normal adult human brain demonstrated TSH-R and TG in cortical neurons and cerebral vasculature, respectively, within various brain areas...
August 3, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28743894/creb-regulates-distinct-adaptive-transcriptional-programs-in-astrocytes-and-neurons
#2
Luis Pardo, Luis Miguel Valor, Abel Eraso-Pichot, Angel Barco, Arantxa Golbano, Giles E Hardingham, Roser Masgrau, Elena Galea
The cyclic AMP response element binding protein (CREB) is a primary hub of activity-driven genetic programs in neurons controlling plasticity, neurogenesis and survival. By contrast, the gene networks coordinated by CREB in astrocytes are unknown despite the fact that the astrocytic CREB is also activity-driven and neuroprotective. Herein we identified the transcriptional programs regulated by CREB in astrocytes as compared to neurons using, as study materials, transcriptome databases of astrocyte exposed to well-known activators of CREB-dependent transcription as well as publicly available transcriptomes of neuronal cultures...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733161/functional-determination-of-the-differentiation-potential-of-ventral-mesencephalic-neural-precursor-cells-during-dopaminergic-neurogenesis
#3
Gilda Guerrero-Flores, Aimée Bastidas-Ponce, Omar Collazo-Navarrete, Magdalena Guerra-Crespo, Luis Covarrubias
The ventral mesencephalic neural precursor cells (vmNPCs) that give rise to dopaminergic (DA) neurons have been identified by the expression of distinct genes (e.g., Lmx1a, Foxa2, Msx1/2). However, the commitment of these NPCs to the mesencephalic DA neuronal fate has not been functionally determined. Evaluation of the plasticity of vmNPCs suggests that their commitment occurs after E10.5. Here we show that E9.5 vmNPCs implanted in an ectopic area of E10.5 mesencephalic explants, retained their specification marker Lmx1a and efficiently differentiated into neurons but did not express the gene encoding tyrosine hydroxylase (Th), the limiting enzyme for dopamine synthesis...
September 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28701919/amyloid-%C3%AE-impairs-vesicular-secretion-in-neuronal-and-astrocyte-peptidergic-transmission
#4
Virginia Plá, Neus Barranco, Esther Pozas, Fernando Aguado
Regulated secretion of neuropeptides and neurotrophic factors critically modulates function and plasticity of synapses and circuitries. It is believed that rising amyloid-β (Aβ) concentrations, synaptic dysfunction and network disorganization underlie early phases of Alzheimer's disease (AD). Here, we analyze the impact of soluble Aβ1-42 assemblies on peptidergic secretion in cortical neurons and astrocytes. We show that neurons and astrocytes differentially produce and release carboxypeptidase E (CPE) and secretogranin III (SgIII), two dense-core vesicle (DCV) markers belonging to the regulated secretory pathway...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28700615/astrocyte-heterogeneity-across-the-brain-and-spinal-cord-occurs-developmentally-in-adulthood-and-in-response-to-demyelination
#5
Hyesook Yoon, Grant Walters, Alex R Paulsen, Isobel A Scarisbrick
Astrocytes have emerged as essential regulators of function and response to injury in the brain and spinal cord, yet very little is known about regional differences that exist. Here we compare the expression of key astroglial markers (glial fibrillary acidic protein (GFAP) and Aldehyde Dehydrogenase-1 Family Member L1 (ALDH1L1)) across these disparate poles of the neuraxis, tracking their expression developmentally and in the context of demyelination. In addition, we document changes in the astrocyte regulatory cytokine interleukin 6 (IL-6), and its signaling partner signal transducer and activator of transcription 3 (STAT3), in vivo and in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28699522/targeting-human-astrocytes-calcium-sensing-receptors-for-treatment-of-alzheimer-s-disease
#6
Anna Chiarini, Ubaldo Armato, James F Whitfield, Ilaria Dal Pra
Understanding the pathophysiology of Alzheimer's disease (AD) in the principal human neural cells is necessary for finding therapeutics for this illness. To help do this, we have been using freshly cultured functionally normal cerebral cortical adult human astrocytes (NAHAs) and postnatal neurons. The findings show that amyloid-β oligomers (Aβ-os) binding to calcium-sensing receptors (CaSRs) on NAHAs and neuron surfaces trigger signals capable of driving AD pathogenesis. This Aβ•CaSR signalling shifts the amyloid precursor protein (APP) from its α-secretase shedding producing neurotrophic/neuroprotective soluble (s)APPα to its β-secretase cleaving engendering AD-driving Aβ42/Aβ42-os peptides...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28694255/soluble-app-functions-as-a-vascular-niche-signal-that-controls-adult-neural-stem-cell-number
#7
Yuya Sato, Yutaka Uchida, Jingqiong Hu, Tracy L Young-Pearse, Takako Niikura, Yoh-Suke Mukouyama
What controls neural stem cell (NSC) number in the neurogenic regions of the adult brain? Vascular niche signals regulate NSC quiescence and growth. Here, we have uncovered a role for soluble amyloid precursor protein (sAPP) as a vascular niche signal in the subventricular zone (SVZ) of the lateral ventricle of the adult brain. sAPP suppresses NSC growth in culture. Further in vivo studies on the role of APP for the NSC number in the SVZ clearly demonstrate that endothelial deletion of App causes a significant increase in the number of BrdU(+) label-retaining NSCs in the SVZ, while NSC/astrocyte deletion of App has no detectable effect on the NSC number...
July 10, 2017: Development
https://www.readbyqxmd.com/read/28665486/uptake-and-metabolism-of-sulphated-steroids-by-the-blood-brain-barrier-in-the-adult-male-rat
#8
M Zeeshan Qaiser, Diana E M Dolman, David J Begley, N Joan Abbott, Mihaela Cazacu-Davidescu, Delia I Corol, Jonathan P Fry
Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism. Using rat brain perfusion in situ, we have found (3) H-PregS to enter more rapidly than (3) H-DHEAS and both to undergo extensive (> 50%) desulphation within 0.5 min of uptake. Enzyme activity for the steroid sulphatase catalysing this deconjugation was enriched in the capillary fraction of the blood-brain barrier and its mRNA expressed in cultures of rat brain endothelial cells and astrocytes...
June 30, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28634469/alexander-disease-mutations-produce-cells-with-coexpression-of-glial-fibrillary-acidic-protein-and-ng2-in-neurosphere-cultures-and-inhibit-differentiation-into-mature-oligodendrocytes
#9
Ulises Gómez-Pinedo, Maria Salomé Sirerol-Piquer, María Durán-Moreno, José Manuel García-Verdugo, Jorge Matias-Guiu
BACKGROUND: Alexander disease (AxD) is a rare disease caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). The disease is characterized by presence of GFAP aggregates in the cytoplasm of astrocytes and loss of myelin. OBJECTIVES: Determine the effect of AxD-related mutations on adult neurogenesis. METHODS: We transfected different types of mutant GFAP into neurospheres using the nucleofection technique. RESULTS: We find that mutations may cause coexpression of GFAP and NG2 in neurosphere cultures, which would inhibit the differentiation of precursors into oligodendrocytes and thus explain the myelin loss occurring in the disease...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28608355/-neuronal-glycolipids-regulate-glial-cell-division-negatively-during-development-and-following-a-lesion
#10
REVIEW
M Nieto-Sampedro, V C Muneton-Gomez
Glial cells in the central nervous system of adult mammals outnumber neurons 10-fold. Their number remains stationary throughout adulthood, controlled by the concomitant presence of mitogens and mitogen inhibitors. The most abundant inhibitor, neurostatin, is ganglioside GD1b O-acetylated on hydroxyl 9 of its outermost sialic acid. Neurostatin inhibited the proliferation of primary microglia and astroblasts in culture (cytostatic) as well as both rodent and human glioma cells (cytotoxic) at nanomolar concentrations...
June 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28606781/sab-is-differentially-expressed-in-the-brain-and-affects-neuronal-activity
#11
Alejandro O Sodero, Monica Rodriguez-Silva, Chiara Salio, Marco Sassoè-Pognetto, Jeremy W Chambers
Sab (SH3 binding protein 5 or SH3BP5) is a mitochondrial scaffold protein involved in signaling associated with mitochondrial dysfunction and apoptosis; furthermore, Sab is a crucial signaling platform for neurodegenerative disease. To determine how this signaling nexus could have a significant effect on disease, we examined the regional abundance of Sab in the brain and sub-neuronal distribution, and we monitored the effect of Sab-mediated signaling on neuronal activity. We found that Sab is widely expressed in the adult mouse brain with increased abundance in hippocampus, ventral midbrain, and cerebellum...
June 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28565827/neuroprotective-effect-of-combining-tanshinone-iia-with-low-dose-methylprednisolone-following-acute-spinal-cord-injury-in-rats
#12
Nian-Wei Yao, Yuan Lu, Li-Qi Shi, Feng Xu, Xian-Hua Cai
The present study compared the potential neuroprotective effect of tanshinone IIA (TIIA) monotherapy, methylprednisolone (MP) monotherapy and combined treatment in an adult acute spinal cord injury (ASCI) rat model. The current study used the weight-drop method (Allen's Impactor) in the rat model and the mechanical scratch method in primary spinal cord neuron culture to determine whether the combined treatment was able to reduce the required dosage of MP in the treatment of ASCI to produce a similar or improved therapeutic effect...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28560414/bone-marrow-stromal-cells-promote-neuromotor-functional-recovery-via-upregulation-of-neurotrophic-factors-and-synapse-proteins-following-traumatic-brain-injury-in-rats
#13
Yan Feng, Yaru Ju, Jianzhong Cui, Liqun Wang
It has previously been demonstrated that bone marrow stromal cells (BMSCs) exhibit great therapeutic potential in neuronal injuries; however, there is limited understanding of the precise underlying mechanisms that contribute to functional improvement following brain injury. The aim of the present study was to assess the effect of BMSC treatment on traumatic brain injury (TBI) in rats, and investigate if they migrate to injured areas and promote neuromotor functional recovery via upregulation of neurotrophic factors and synaptic proteins...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28522364/inhibition-of-mir-181a-protects-female-mice-from-transient-focal-cerebral-ischemia-by-targeting-astrocyte-estrogen-receptor-%C3%AE
#14
Creed M Stary, Lijun Xu, Le Li, Xiaoyun Sun, Yi-Bing Ouyang, Xiaoxing Xiong, Jing Zhao, Rona G Giffard
Whether the effect of miR-181a is sexually dimorphic in stroke is unknown. Prior work showed protection of male mice with miR-181a inhibition. Estrogen receptor-α (ERα) is an identified target of miR181 in endometrium. Therefore we investigated the separate and joint effects of miR-181a inhibition and 17β-estradiol (E2) replacement after ovariectomy. Adult female mice were ovariectomized and implanted with an E2- or vehicle-containing capsule for 14d prior to 1h middle cerebral artery occlusion (MCAO). Each group received either miR-181a antagomir or mismatch control by intracerebroventricular injection 24h before MCAO...
July 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28521131/diverse-requirements-for-microglial-survival-specification-and-function-revealed-by-defined-medium-cultures
#15
Christopher J Bohlen, F Chris Bennett, Andrew F Tucker, Hannah Y Collins, Sara B Mulinyawe, Ben A Barres
Microglia, the resident macrophages of the CNS, engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-β2, and cholesterol...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28499803/establishment-and-characterization-of-primary-astrocyte-culture-from-adult-mouse-brain
#16
Xiu Sun, Xin Hu, Dan Wang, Yimin Yuan, Shangyao Qin, Zijian Tan, Yakun Gu, Xiao Huang, Cheng He, Zhida Su
As a major class of glial cells, astrocytes have been indicated to play multi-roles in physiological and pathological brain. Astrocyte cultures derived from postnatal mouse brains have been extensively used to characterize their biological properties. However, the inability to culture adult mouse primary astrocytes has long stymied studies of function in adult brain. Here, we developed a protocol to successfully establish highly enriched astrocyte cultures from the brains of adult mouse. Cortical tissues were collected to prepare cell suspension by enzymatic digestion and mechanical dissociation, and then plated onto vessels pre-coated with gelatin and matrigel and cultured in DMEM medium containing 20% fetal bovine serum (FBS)...
June 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28485896/sonic-hedgehog-signalling-mediates-astrocyte-crosstalk-with-neurons-to-confer-neuroprotection
#17
Christopher I Ugbode, Imogen Smith, Benjamin J Whalley, Warren D Hirst, Marcus Rattray
Sonic hedgehog (SHH) is a glycoprotein associated with development that is also expressed in the adult CNS and released after brain injury. Since the SHH receptors patched homolog-1 and Smoothened are highly expressed on astrocytes, we hypothesized that SHH regulates astrocyte function. Primary mouse cortical astrocytes derived from embryonic Swiss mouse cortices, were treated with two chemically distinct agonists of the SHH pathway, which caused astrocytes to elongate and proliferate. These changes are accompanied by decreases in the major astrocyte glutamate transporter-1 and the astrocyte intermediate filament protein glial fibrillary acidic protein...
May 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28473749/amyloid-%C3%AE-exposed-human-astrocytes-overproduce-phospho-tau-and-overrelease-it-within-exosomes-effects-suppressed-by-calcilytic-nps-2143-further-implications-for-alzheimer-s-therapy
#18
Anna Chiarini, Ubaldo Armato, Emanuela Gardenal, Li Gui, Ilaria Dal Prà
The two main drivers of Alzheimer's disease (AD), amyloid-β (Aβ) and hyperphosphorylated Tau (p-Tau) oligomers, cooperatively accelerate AD progression, but a hot debate is still ongoing about which of the two appears first. Here we present preliminary evidence showing that Tau and p-Tau are expressed by untransformed cortical adult human astrocytes in culture and that exposure of such cells to an Aβ42 proxy, Aβ25-35, which binds the calcium-sensing receptor (CaSR) and activates its signaling, significantly increases intracellular p-Tau levels, an effect CaSR antagonist (calcilytic) NPS 2143 wholly hinders...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28470822/pericyte-derived-bone-morphogenetic-protein-4-underlies-white-matter-damage-after-chronic-hypoperfusion
#19
Maiko T Uemura, Masafumi Ihara, Takakuni Maki, Takayuki Nakagomi, Seiji Kaji, Kengo Uemura, Tomohiro Matsuyama, Raj N Kalaria, Ayae Kinoshita, Ryosuke Takahashi
Subcortical small vessel disease (SVD) is characterized by white matter damage resulting from arteriolosclerosis and chronic hypoperfusion. Transforming growth factor beta 1 (TGFB1) is dysregulated in the hereditary SVD, CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy). However, very little is known about the role of the largest group in the TGFB superfamily - the bone morphogenetic proteins (BMPs) - in SVD pathogenesis. The aim of this study was to characterize signaling abnormalities of BMPs in sporadic SVD...
May 4, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28467894/potential-mechanisms-of-development-dependent-adverse-effects-of-the-herbicide-paraquat-in-3d-rat-brain-cell-cultures
#20
J Sandström, A Broyer, D Zoia, C Schilt, C Greggio, M Fournier, K Q Do, F Monnet-Tschudi
Exposure to environmental toxicants during vulnerable windows of brain development is suspected to raise the prevalence for neurological dysfunctions at later stages in life. Differentiation processes and changes in morphology, as well as a lack of physiological barriers, might be reasons that render a developing brain more susceptible to neurotoxicants than an adult. However, also the intrinsic capacity of cells to combat toxicant induced cellular stress might differ between the immature- and mature brain...
April 30, 2017: Neurotoxicology
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