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Virawudh Soontornniyomkij, Anya Umlauf, Benchawanna Soontornniyomkij, Ben Gouaux, Ronald J Ellis, Andrew J Levine, David J Moore, Scott L Letendre
OBJECTIVE: Antiretroviral therapy (ART) is currently recommended for all persons living with HIV (PLWH), regardless of their CD4+ T-cell count, and should be continued throughout life. Nonetheless, vigilance of the safety of ART, including its neurotoxicity, must continue. We hypothesized that use of certain ART drugs might be associated with aging-related cerebral degenerative changes among PLWH. DESIGN: Clinicopathological study of PLWH who were using ART drugs at the last clinical assessment...
June 14, 2018: AIDS
Ednilse Leme, Ericka P Silva, Paula S Rodrigues, Igor R Silva, Maria F M Martins, Eduardo F Bondan, Maria M Bernardi, Thiago B Kirsten
The Billings reservoir is the largest water-storage facility in the São Paulo Metropolitan Region, with only a small part of the reservoir used for water supply. Recently, the São Paulo Metropolitan Region has experienced the greatest water collapse ever recorded. Thus, the intensification of use of the Billings reservoir should be considered. The objective of this study was to evaluate the quality of the water from different areas of the Billings reservoir related to human consumption (water supply and fishing): Rio Pequeno, Rio Grande, and Bororé rivers...
June 11, 2018: Ecotoxicology and Environmental Safety
F Ruffinatti, L Tapella, I Gregnanin, A Stevano, G Chiorino, P L Canonico, C Distasi, A A Genazzani, D Lim
BACKGROUND: It is well known that alterations in astrocytes occur in Alzheimer's Disease and reactive astrogliosis is one of the hallmarks of the disease. Recently, data has emerged that suggests that alterations in astrocytes may also occur early in the pathogenesis of the disease. OBJECTIVE: The aim of present work was to characterize the transcriptional alterations occurring in cultured astrocytes from 3xTg-AD mouse pups compared to control non-transgenic mice...
June 12, 2018: Current Alzheimer Research
Justine Renaud, Valentina Bassareo, Jimmy Beaulieu, Annalisa Pinna, Michele Schlich, Carole Lavoie, Daniela Murtas, Nicola Simola, Maria-Grazia Martinoli
Epidemiological evidence suggests a correlation between diabetes and age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Hyperglycemia causes oxidative stress in vulnerable tissues such as the brain. We recently demonstrated that elevated levels of glucose lead to the death of dopaminergic neurons in culture through oxidative mechanisms. Considering the lack of literature addressing dopaminergic alterations in diabetes with age, the goal of this study was to characterize the state of 2 critical dopaminergic pathways in the nicotinamide-streptozotocin rat model of long-term hyperglycemia, specifically the nigrostriatal motor pathway and the reward-associated mesocorticolimbic pathway...
May 14, 2018: Neurobiology of Aging
Maria Meyer, Agustina Lara, Hazel Hunt, Joseph Belanoff, E Ronald de Kloet, Maria Claudia Gonzalez Deniselle, Alejandro F De Nicola
Wobbler mice are experimental models for amyotrophic lateral sclerosis. As such they show motoneuron degeneration, motor deficits, and astrogliosis and microgliosis of the spinal cord. Additionally, Wobbler mice show increased plasma, spinal cord and brain corticosterone levels and focal adrenocortical hyperplasia, suggesting a pathogenic role for glucocorticoids in this disorder. Considering this endocrine background, we examined whether the glucocorticoid receptor (GR) modulator CORT 113176 prevents spinal cord neuropathology of Wobblers...
June 8, 2018: Neuroscience
Rong Li, Sudhanshu Sahu, Melitta Schachner
BACKGROUND: Neural cell adhesion molecule L1 contributes to nervous system development and maintenance by promoting neuronal survival, neuritogenesis, axonal regrowth/sprouting, myelination, and synapse formation and plasticity. L1 also enhances recovery after spinal cord injury and ameliorates neurodegenerative processes in experimental rodent models. Aiming for clinical translation of L1 into therapy we screened for and functionally characterized in vitro the small organic molecule phenelzine, which mimics characteristic L1 functions...
June 6, 2018: Restorative Neurology and Neuroscience
Andrew C Gill, Andrew R Castle
The cellular prion protein, PrPC , is a small, cell surface glycoprotein with a function that is currently somewhat ill defined. It is also the key molecule involved in the family of neurodegenerative disorders called transmissible spongiform encephalopathies, which are also known as prion diseases. The misfolding of PrPC to a conformationally altered isoform, designated PrPTSE , is the main molecular process involved in pathogenesis and appears to precede many other pathologic and clinical manifestations of disease, including neuronal loss, astrogliosis, and cognitive loss...
2018: Handbook of Clinical Neurology
Alfonso Grimaldi, Carlo Brighi, Giovanna Peruzzi, Davide Ragozzino, Valentina Bonanni, Cristina Limatola, Giancarlo Ruocco, Silvia Di Angelantonio
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. In the pathogenesis of AD a pivotal role is played by two neurotoxic proteins that aggregate and accumulate in the central nervous system: amyloid beta and hyper-phosphorylated tau. Accumulation of extracellular amyloid beta plaques and intracellular hyper-phosphorylated tau tangles, and consequent neuronal loss begins 10-15 years before any cognitive impairment. In addition to cognitive and behavioral deficits, sensorial abnormalities have been described in AD patients and in some AD transgenic mouse models...
June 7, 2018: Cell Death & Disease
Yong Yang, Jie Ren, Yuhao Sun, Yuan Xue, Zhijian Zhang, Aihua Gong, Baofeng Wang, Zhihong Zhong, Zhenwen Cui, Zhiyu Xi, Guo-Yuan Yang, Qingfang Sun, Liuguan Bian
Reactive astrogliosis is a common response to insults to the central nervous system, but the mechanism remains unknown. In this study, we found the temporal and spatial differential expression of glial fibrillary acidic protein (GFAP) and Vimentin in the intracerebral hemorrhage (ICH) mouse brain, indicating that the de-differentiation and astroglial-mesenchymal transition (AMT) of astrocytes might be an early event in reactive astrogliosis. Further we verified the AMT finding in purified astrocyte cultures exposed to hemoglobin (Hb)...
June 7, 2018: Cell Death and Differentiation
Yehao Zhang, Jianxun Liu, Bin Yang, Yongqiu Zheng, Mingjiang Yao, Mingqian Sun, Li Xu, Chengren Lin, Dennis Chang, Fangze Tian
Background: Astrogliosis has the potential to lead to harmful effects, namely, neuroinflammation, and to interfere with synapse sprouting. Previous studies have suggested that Lipocalin-2 (LCN2) acts as a key target in regulating the reaction of astrocytes. However, the underlying molecular mechanism is not fully elucidated. In the present study, we examined the neuroprotective and anti-inflammatory effects of Ginkgo biloba extract (EGB), a well-known extract with potential immunoregulatory properties in the nervous system...
2018: Frontiers in Pharmacology
Ann Tenneil O'Connor, Michelle A Clark
The presence of a brain renin angiotensin system (RAS) is well documented. An overactive brain RAS contributes to the development and progression of cardiovascular and renal disorders among other conditions. In hypertension, an augmented brain RAS leads to an increase in sympathetic nervous system activity. In addition, impaired baroreceptor reflex function, increased vasopressin activity and neuroinflammation are important contributors as well. The relevance of angiotensins in central and peripheral systems, such as neurons and vascular smooth muscle cells, in cardiovascular disease pathogenesis is fairly understood...
June 1, 2018: Neurochemical Research
Yasuhiro Ogawa, Masahiro Irisa, Takafumi Sano, Yusuke Yanagi, Eiri Furusawa, Takahiro Saito, Shoji Yamanaka, Kohji Itoh, Hitoshi Sakuraba, Kazuhiko Oishi
Sandhoff disease (SD) is a genetic disorder caused by a mutation of the β-subunit gene β-hexosaminidase B (HexB) in humans, which results in the massive accumulation of the ganglioside GM2 and related glycosphingolipids in the nervous system. SD causes progressive neurodegeneration and changes in white matter in human infants. An animal model of SD has been established, Hexb-deficient (Hexb) mice, which shows abnormalities resembling the severe phenotype found in human infants. Previously, we reported that the activation state of microglia caused astrogliosis in the early stage of Hexb mouse development...
May 29, 2018: Neuroreport
Rasha B Abd-Ellatief, Heba K Mohamed, Hassan I Kotb
To our knowledge, this is the first study which investigates the induction of neuroinflammation in rats using an acidic-saline model of fibromyalgia. It is well known that the hippocampus has a fundamental role in pain perception, and astrocytes play a crucial role in pain signaling. Our aim is to evaluate the ability of dexmedetomidine to attenuate the inflammatory responses induced in astrocytes. In a group of healthy rats, induction of chronic muscle pain by intramuscular injection of 100 µL of acidic saline on days 0 and 5 resulted in peripheral sensitization (measured using the von Frey test) and significant (p < 0...
May 29, 2018: Cells, Tissues, Organs
Ewelina Kurtys, Cindy Casteels, Caroline C Real, Ulrich L M Eisel, J Martin Verkuyl, Laus M Broersen, Hans C Klein, Rudi A J O Dierckx, Janine Doorduin, Erik F J de Vries
INTRODUCTION: A possible target for stroke management is modulation of neuroinflammation. Evidence suggests that food components may exert anti-inflammatory properties and thus may reduce stroke-induced brain damage. AIM: To investigate the efficacy of a diet, containing anti-inflammatory ingredients, as treatment for focal ischemic brain damage induced by photothrombotic stroke in the somatosensory cortex of rats. RESULTS: Brain lesions were surrounded by strong astrogliosis on both day 7 and day 21 after stroke and were accompanied by a trend toward globally decreased glucose metabolism on day 7...
May 27, 2018: CNS Neuroscience & Therapeutics
Laila Abdel-Hafiz, Andreas Müller-Schiffmann, Carsten Korth, Benedetta Fazari, Owen Y Chao, Susanne Nikolaus, Sandra Schäble, Arne Herring, Kathy Keyvani, Valéria Lamounier-Zepter, Joseph P Huston, Maria A de Souza Silva
We examined behaviors and neurotransmitter levels in the tgDimer mouse, a model for early Alzheimer's disease, that expresses exclusively soluble amyloid beta (Aβ) dimers and is devoid of Aβ plaques, astrogliosis, and neuroinflammation. Seven-month-old mice were subjected to tests of motor activity, attention, anxiety, habituation learning, working memory, and depression-related behaviors. They were impaired in nonselective attention and motor learning and showed anxiety- and despair-related behaviors. In 7- and 12-month-old mice, levels of acetylcholine, dopamine, and serotonin were measured in neostriatum, ventral striatum, prefrontal cortex, hippocampus, amygdala, and entorhinal cortex by high-performance liquid chromatography...
April 17, 2018: Neurobiology of Aging
Andrea Conte, Giovanna Maria Pierantoni
The homeodomain-interacting protein kinases (HIPKs) HIPK1, HIPK2 and HIPK3 are Ser/Thr kinases which interact with homeobox proteins and other transcription factors, acting as transcriptional coactivators or corepressors. HIPKs contribute to regulating several biological processes, such as signal transduction, apoptosis, embryonic development, DNA-damage response, and cellular proliferation, in response to various extracellular stimuli. Recently it has emerged that, in addition to their role in cancer, fibrosis and diabetes, HIPKs may also be involved in other human diseases, including amyotrophic lateral sclerosis (ALS), Rett syndrome, cerebellar diseases, and retinal vascular dysfunction...
May 24, 2018: MicroRNA
Xiang Yin, Shuyu Wang, Yan Qi, Xudong Wang, Hongquan Jiang, Tianhang Wang, Yueqing Yang, Ying Wang, Chunting Zhang, Honglin Feng
AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A -positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling...
May 16, 2018: Molecular and Cellular Neurosciences
Clara Quintas, Nuno Vale, Jorge Gonçalves, Glória Queiroz
Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog...
2018: Frontiers in Pharmacology
Petr Krupa, Irena Vackova, Jiri Ruzicka, Kristyna Zaviskova, Jana Dubisova, Zuzana Koci, Karolina Turnovcova, Lucia Machova Urdzikova, Sarka Kubinova, Svatopluk Rehak, Pavla Jendelova
Human mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) were used for the treatment of the ischemic-compression model of spinal cord injury in rats. To assess the effectivity of the treatment, different dosages (0.5 or 1.5 million cells) and repeated applications were compared. Cells or saline were applied intrathecally by lumbar puncture for one week only, or in three consecutive weeks after injury. Rats were assessed for locomotor skills (BBB, rotarod, flat beam) for 9 weeks. Spinal cord tissue was morphometrically analyzed for axonal sprouting, sparing of gray and white matter and astrogliosis...
May 17, 2018: International Journal of Molecular Sciences
Alfonso Grimaldi, Giuseppina D'Alessandro, Maria Amalia Di Castro, Clotilde Lauro, Vikrant Singh, Francesca Pagani, Luigi Sforna, Francesca Grassi, Silvia Di Angelantonio, Luigi Catacuzzeno, Heike Wulff, Cristina Limatola, Myriam Catalano
Glial cells actively maintain the homeostasis of brain parenchyma, regulating neuronal excitability and preserving the physiological composition of the extracellular milieu. Under pathological conditions, some functions of glial cells could be compromised, exacerbating the neurotoxic processes. We investigated if the homeostatic activities of astrocytes and microglia could be modulated by the voltage-gated K+ channel Kv1.3. To this end we used in vitro and in vivo systems to model cell-to-cell interactions in tumoral conditions, using a specific inhibitor of Kv1...
May 16, 2018: Scientific Reports
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