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https://www.readbyqxmd.com/read/27906174/therapeutic-advantage-of-pro-electrophilic-drugs-to-activate-the-nrf2-are-pathway-in-alzheimer-s-disease-models
#1
Stuart A Lipton, Tayebeh Rezaie, Anthony Nutter, Kevin M Lopez, James Parker, Kunio Kosaka, Takumi Satoh, Scott R McKercher, Eliezer Masliah, Nobuki Nakanishi
Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27905510/remarkable-alterations-of-nav1-6-in-reactive-astrogliosis-during-epileptogenesis
#2
Hongyan Zhu, Yuxiao Zhao, Hao Wu, Nan Jiang, Ziyi Wang, Weide Lin, Jiahui Jin, Yonghua Ji
Voltage-gated sodium channels (VGSCs) play a vital role in controlling neuronal excitability. Nav1.6 is the most abundantly expressed VGSCs subtype in the adult central nervous system and has been found to contribute to facilitate the hyperexcitability of neurons after electrical induction of status epilepticus (SE). To clarify the exact expression patterns of Nav1.6 during epileptogenesis, we examined the expression of Nav1.6 at protein and mRNA levels in two distinct animal models of temporal lobe epilepsy (TLE) including a post-SE model induced by kainic acid (KA) intrahippocampal injection and a kindling model evoked by pentylenetetrazole (PTZ)...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904823/expression-of-gp91phox-and-p22phox-catalytic-subunits-of-nadph-oxidase-on-microglia-in-nasu-hakola-disease-brains
#3
Jun-Ichi Satoh, Yoshihiro Kino, Motoaki Yanaizu, Youhei Tosaki, Kenji Sakai, Tusyoshi Ishida, Yuko Saito
The superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex of phagocytes (phox) plays a key role in production of reactive oxygen species (ROS) by microglia. The catalytic subunits of the NADPH oxidase are composed of p22phox and gp91phox. Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder caused by a loss-of-function mutation of either TYROBP (DAP12) or TREM2. Pathologically, the brains of NHD patients exhibit extensive demyelination designated leukoencephalopathy, astrogliosis, accumulation of axonal spheroids, and remarkable activation of microglia predominantly in the white matter of frontal and temporal lobes...
November 2016: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/27899230/experimental-zika-virus-infection-induces-spinal-cord-injury-and-encephalitis-in-newborn-swiss-mice
#4
Natália C C A Fernandes, Juliana S Nogueira, Rodrigo A Réssio, Cinthya S Cirqueira, Lidia M Kimura, Karolina R Fernandes, Mariana S Cunha, Renato P Souza, Juliana M Guerra
A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America, with neurological symptons including meningoencephalitis and Guillain-Barré syndrome in adults, besides an apparent increased incidence of microcephaly in infants born to infected mothers. It is becoming a necessity to have a trustworthy animal model to better understand ZIKV infection. In this study we used newborn white Swiss mice as a model to investigate the ZIKV strain recently isolated in Brazil. ZIKV was inoculated via intracerebral and subcutaneous routes and analysed through gross histopathology and immunohistochemistry...
November 26, 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27895121/neuronal-mtorc1-is-required-for-maintaining-the-nonreactive-state-of-astrocytes
#5
Yue Zhang, Song Xu, Kang-Yan Liang, Kai Li, Zhi-Peng Zou, Cui-Lan Yang, Kang Tan, Xiong Cao, Yu Jiang, Tian-Ming Gao, Xiao-Chun Bai
Astrocytes respond to central nervous system (CNS) insults through reactive astrogliosis, but the underlying mechanisms are unclear. In this study, we show that inactivation of mechanistic target of rapamycin complex (mTORC1) signaling in postnatal neurons induces reactive astrogliosis in mice. Ablation of Raptor (an mTORC1-specific component) in postmitotic neurons abolished mTORC1 activity and produced neurons with smaller soma and fewer dendrites, resulting in microcephaly and aberrant behavior in adult mice...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27886261/neil3-induced-neurogenesis-protects-against-prion-disease-during-the-clinical-phase
#6
Clara M O Jalland, Katja Scheffler, Sylvie L Benestad, Torfinn Moldal, Cecilie Ersdal, Gjermund Gunnes, Rajikala Suganthan, Magnar Bjørås, Michael A Tranulis
Base excision repair (BER) is the major pathway for repair of oxidative DNA damage. Mice with genetic knockout of the BER enzyme Neil3 display compromised neurogenesis in the sub-ventricular zone of the lateral ventricle and sub-granular layer of the dentate gyrus of the hippocampus. To elucidate the impact of oxidative DNA damage-induced neurogenesis on prion disease we applied the experimental prion disease model on Neil3-deficient mice. The incubation period for the disease was similar in both wild type and Neil3(-/-) mice and the overall neuropathology appeared unaffected by Neil3 function...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27885490/localized-cortical-chronic-traumatic-encephalopathy-pathology-after-single-severe-axonal-injury-in-human-brain
#7
Sharon B Shively, Sarah L Edgerton, Diego Iacono, Dushyant P Purohit, Bao-Xi Qu, Vahram Haroutunian, Kenneth L Davis, Ramon Diaz-Arrastia, Daniel P Perl
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangles), astrocytes and cell processes distributed around small blood vessels at sulcal depths in irregular patterns within the cortex. The pathophysiological mechanism for this lesion is unknown. Moreover, a subset of CTE cases harbors cortical β-amyloid plaques...
November 24, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27884163/chronic-adiponectin-deficiency-leads-to-alzheimer-s-disease-like-cognitive-impairments-and-pathologies-through-ampk-inactivation-and-cerebral-insulin-resistance-in-aged-mice
#8
Roy Chun-Laam Ng, On-Yin Cheng, Min Jian, Jason Shing-Cheong Kwan, Philip Wing-Lok Ho, Kenneth King-Yip Cheng, Patrick Ka Kit Yeung, Lena Lei Zhou, Ruby Lai-Chong Hoo, Sookja Kim Chung, Aimin Xu, Karen Siu-Ling Lam, Koon Ho Chan
BACKGROUND: Insulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM...
November 25, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27878757/targeting-ccr3-to-reduce-amyloid-%C3%AE-production-tau-hyperphosphorylation-and-synaptic-loss-in-a-mouse-model-of-alzheimer-s-disease
#9
Chunyan Zhu, Bing Xu, Xiaohong Sun, Qiwen Zhu, Yi Sui
The majority of Alzheimer's disease (AD) patients have a late onset, and chronic neuroinflammation, characterized by glial activation and secretion of pro-inflammatory cytokines and chemokines, plays a role in the pathogenesis of AD. The chemokine CCL11 has been shown to be a causative factor of cognitive decline in the process of aging, but little is known whether it is involved in the pathogenesis of AD. In the present study, we showed that CCR3, the receptor for CCL11, was expressed by hippocampal neurons and treatment of primary hippocampal neuronal cultures (14 days in vitro) with CCL11 resulted in activation of cyclin-dependent kinase 5 and glycogen synthase kinase-3β, associated with elevated tau phosphorylation at multiple sites...
November 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27873132/mechanisms-of-excessive-extracellular-glutamate-accumulation-in-temporal-lobe-epilepsy
#10
Jan Albrecht, Magdalena Zielińska
There is compelling evidence that initiation and maintenance of epileptic seizures in temporal lobe epilepsy (TLE) is facilitated by excessive accumulation in the extracellular (perisynaptic) space of the excitatory neurotransmitter glutamate (Glu). This review discusses the mechanisms underlying this phenomenon. Glu released from neurons is taken up by astrocytes and activated there by glutamine synthetase (GS) to form glutamine (Gln) which upon entry to neurons is degraded back to Glu by phosphate-activated glutaminase (PAG): this chain of reactions has been defined as the glutamine/glutamate/cycle (GGC)...
November 21, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27864839/reduction-of-the-foreign-body-response-and-neuroprotection-by-apyrase-and-minocycline-in-chronic-cannula-implantation-in-the-rat-brain
#11
Linda Hayn, Linda Deppermann, Michael Koch
Implantation of electrodes or cannulae into the brain is accompanied by a tissue response referred to as foreign body response. Adenosine triphosphate (ATP) is one of the signalling molecules released by injured cells which mediate the chemoattraction of microglial cells. The constitutive release of pro-inflammatory and cytotoxic substances by microglial cells in chronic implants exacerbates neuronal cell death and the immune response. This study aimed to interfere with the initial events of the foreign body response in order to mitigate neurotoxicity and inflammation...
November 19, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27864825/individual-hippocampal-subfield-assessment-indicates-that-matrix-macromolecules-and-gliosis-are-key-elements-for-the-increased-t2-relaxation-time-seen-in-temporal-lobe-epilepsy
#12
Jose Eduardo Peixoto-Santos, Ludmyla Kandratavicius, Tonicarlo Rodrigues Velasco, Joao Alberto Assirati, Carlos Gilberto Carlotti, Renata Caldo Scandiuzzi, Carlos Ernesto Garrido Salmon, Antonio Carlos Dos Santos, Joao Pereira Leite
OBJECTIVE: Increased T2 relaxation time is often seen in temporal lobe epilepsy (TLE) with hippocampal sclerosis. Water content directly affects the effective T2 in a voxel. Our aim was to evaluate the relation between T2 values and two molecules associated with brain water homeostasis aquaporin 4 (AQP4) and chondroitin sulfate proteoglycan (CSPG), as well as cellular populations in the hippocampal region of patients with TLE. METHODS: Hippocampal T2 imaging and diffusion tensor imaging (DTI) were obtained from 42 drug-resistant patients with TLE and 20 healthy volunteers (radiologic controls, RCs)...
November 18, 2016: Epilepsia
https://www.readbyqxmd.com/read/27864463/increased-brain-hemopexin-levels-improve-outcomes-after-intracerebral-hemorrhage
#13
Jenna L Leclerc, Juan Santiago-Moreno, Alex Dang, Andrew S Lampert, Pedro E Cruz, Awilda M Rosario, Todd E Golde, Sylvain Doré
Following intracerebral hemorrhage (ICH), extracellular heme precipitates secondary brain injury, which results in irreversible brain damage and enduring neurological deficits. Hemopexin (Hpx) is an endogenous protein responsible for scavenging heme, thereby modulating its intrinsic proxidant/proinflammatory properties. Although Hpx is present in the brain, the endogenous levels are insufficient to combat the massive heme overload following ICH. We hypothesized that increasing brain Hpx levels would improve ICH outcomes...
November 18, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27860453/targeting-the-d-series-resolvin-receptor-system-for-the-treatment-of-osteoarthritic-pain
#14
Junting Huang, James J Burston, Li Li, Sadaf Ashraf, Paul I Mapp, Andrew J Bennett, Srinivasarao Ravipati, Petros Pousinis, David A Barrett, Brigitte E Scammell, Victoria Chapman
OBJECTIVE: Pain is a major symptom of osteoarthritis (OA); current analgesics either do not offer adequate pain relief or are associated with serious side effects. Herein we have investigated the therapeutic potential of targeting the resolvin receptor system to modify OA pain and pathology. METHODS: Gene expression of two resolvin receptors (ALX and ChemR23) was quantified in synovia and medial tibial plateau collected from patients at joint replacement for OA...
November 16, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27856824/all-trans-retinoic-acid-augments-the-histopathological-outcome-of-neuroinflammation-and-neurodegeneration-in-lupus-prone-mrl-lpr-mice
#15
Michelle H Theus, Joshua B Sparks, Xiaofeng Liao, Jingjing Ren, Xin M Luo
Recently, we demonstrated that treatment with all-trans-retinoic acid (tRA) induced a paradoxical effect on immune activation during the development of autoimmune lupus. Here, we further describe its negative effects on mediating neuroinflammation and neurodegeneration. Female MRL/lpr mice were orally administered tRA or VARA (retinol mixed with 10% tRA) from 6 to 14 weeks of age. Both treatments had a significant effect on brain weight, which correlated with histopathological evidence of focal astrogliosis, meningitis, and ventriculitis...
November 16, 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/27855618/scutellarin-as-a-therapeutic-agent-in-microglia-mediated-neuroinflammation-in-cerebral-ischemia
#16
Chun-Yun Wu, Ming Fang, Aparna Karthikeyan, Yun Yuan, Eng-Ang Ling
Neuroinflammation plays an important role in different brain diseases including acute brain injuries such as cerebral ischemic stroke and chronic neurodegenerative diseases e.g. Alzheimer's disease etc. The central player in this is the activated microglia which produce substantial amounts of proinflammatory mediators that may exacerbate the disease. Associated with microglia activation is astrogliosis characterized by hypertrophic astrocytes with increased expression of proinflammatory cytokines, neurotrophic factors, stem cell, neuronal and proliferation markers, all these are crucial for reconstruction of damaged tissue and ultimate restoration of neurological functions...
November 18, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27847705/a-model-of-glial-scarring-analogous-to-the-environment-of-a-traumatically-injured-spinal-cord-using-kainate
#17
Jong Yoon Yoo, Chang Ho Hwang, Hea Nam Hong
OBJECTIVE: To develop an in vitro model analogous to the environment of traumatic spinal cord injury (SCI), the authors evaluated change of astrogliosis following treatments with kainate and/or scratch, and degree of neurite outgrowth after treatment with a kainate inhibitor. METHODS: Astrocytes were obtained from the rat spinal cord. Then, 99% of the cells were confirmed to be GFAP-positive astrocytes. For chemical injury, the cells were treated with kainate at different concentrations (10, 50 or 100 µM)...
October 2016: Annals of Rehabilitation Medicine
https://www.readbyqxmd.com/read/27847282/mesenchymal-stem-cell-derived-extracellular-vesicles-ameliorate-inflammation-induced-preterm-brain-injury
#18
Karla Drommelschmidt, Meray Serdar, Ivo Bendix, Josephine Herz, Frederik Bertling, Sebastian Prager, Matthias Keller, Anna-Kristin Ludwig, Vikas Duhan, Stefan Radtke, Kyra de Miroschedji, Peter A Horn, Yohan van de Looij, Bernd Giebel, Ursula Felderhoff-Müser
OBJECTIVE: Preterm brain injury is a major cause of disability in later life, and may result in motor, cognitive and behavioural impairment for which no treatment is currently available. The aetiology is considered as multifactorial, and one underlying key player is inflammation leading to white and grey matter injury. Extracellular vesicles secreted by mesenchymal stem/stromal cells (MSC-EVs) have shown therapeutic potential in regenerative medicine. Here, we investigated the effects of MSC-EV treatment on brain microstructure and maturation, inflammatory processes and long-time outcome in a rodent model of inflammation-induced brain injury...
November 12, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27837318/astrocytes-in-migration
#19
Jiang Shan Zhan, Kai Gao, Rui Chao Chai, Xi Hua Jia, Dao Peng Luo, Guo Ge, Yu Wu Jiang, Yin-Wan Wendy Fung, Lina Li, Albert Cheung Hoi Yu
Cell migration is a fundamental phenomenon that underlies tissue morphogenesis, wound healing, immune response, and cancer metastasis. Great progresses have been made in research methodologies, with cell migration identified as a highly orchestrated process. Brain is considered the most complex organ in the human body, containing many types of neural cells with astrocytes playing crucial roles in monitoring normal functions of the central nervous system. Astrocytes are mostly quiescent under normal physiological conditions in the adult brain but become migratory after injury...
November 11, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27825285/leukemia-inhibitory-factor-contributed-to-reactive-astrogliosis-via-activation-of-stat3-signaling-after-intracerebral-hemorrhage-in-rats
#20
Hua-Jun Zhou, Xi Yang, Han-Jin Cui, Tao Tang, Jian-Hua Zhong, Jie-Kun Luo, A-Li Yang, Qi-Mei Zhang, Jing-Hua Zhou, Qiang Zhang
Reactive astrogliosis has been occurred after intracerebral hemorrhage (ICH). Leukemia inhibitory factor (LIF) can act as a modulator for glial gene expression. Signal transducer and activator of transcription3 (STAT3) is a critical regulator of reactive astrogliosis. The present study tested whether endogenous leukemia inhibitory factor (LIF) acted on intracerebral hemorrhage (ICH)-induced reactive astrogliosis via STAT3 signaling pathway. Rats were divided into three parts of experiments: (1) Rats received either an ICH or a needle insertion (sham)...
November 8, 2016: Journal of Neurotrauma
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