当前位置： SCI文献检索 > EXPERIMENTAL NEUROLOGY期刊下所有文献 > Suppression of adenosine 2a receptor (A2aR)-mediated adenosine signaling improves disease phenotypes in a mouse model of amyotrophic lateral sclerosis.

Suppression of adenosine 2a receptor (A2aR)-mediated adenosine signaling improves disease phenotypes in a mouse model of amyotrophic lateral sclerosis.

Abstract：

:Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease in which the majority of upper and lower motor neurons are degenerated. Despite intensive efforts to identify drug targets and develop neuroprotective strategies, effective therapeutics for ALS remains unavailable. The identification and characterization of novel targets and pathways remain crucial in the development of ALS therapeutics. Adenosine is a major neuromodulator that actively regulates synaptic transmission. Interestingly, adenosine levels are significantly elevated in the cerebrospinal fluid (CSF) of progressing human ALS patients. In the current study, we showed that adenosine 2a receptor (A2aR), but not adenosine 1 receptor (A1R), is highly enriched in spinal (motor) neurons. A2aR expression is also selectively increased at the symptomatic onset in the spinal cords of SOD1G93A mice and end-stage human ALS spinal cords. Interestingly, we found that direct adenosine treatment is sufficient to induce embryonic stem cell-derived motor neuron (ESMN) cell death in cultures. Subsequent pharmacological inhibition and partial genetic ablation of A2aR (A2aR(+/-)) significantly protect ESMN from SOD1G93A(+) astrocyte-induced cell death and delay disease progression of SOD1G93A mice. Taken together, our results provide compelling novel evidence that A2aR-mediated adenosine signaling contributes to the selective spinal motor neuron degeneration observed in the SOD1G93A mouse model of ALS.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Ng SK,Higashimori H,Tolman M,Yang Y

doi

10.1016/j.expneurol.2015.03.004

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

115-22

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(15)00071-0

journal_volume

267

pub_type

杂志文章

相关文献

EXPERIMENTAL NEUROLOGY文献大全
  • Spinal RyR2 pathway regulated by the RNA-binding protein HuD induces pain hypersensitivity in antiretroviral neuropathy.

    abstract：:The antiretroviral toxic neuropathy, a distal sensory polyneuropathy associated with antiretroviral treatment, is a frequently occurring neurological complication during treatment of patients with AIDS and often leads to discontinuation of antiretroviral therapy. The mechanisms by which antiretroviral drugs contribute...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2015.02.036

    authors： Sanna MD,Peroni D,Quattrone A,Ghelardini C,Galeotti N

    更新日期：2015-05-01 00:00:00

  • Tyrosine hydroxylase immunoreactivity and monoamine and metabolite levels in cryopreserved human fetal ventral mesencephalon.

    abstract：:Both fresh and cryopreserved-thawed human fetal ventral mesencephalon have been used for preclinical research and implantation into the brains of patients with Parkinson's disease. Further characterization and an evaluation of the effects of cryopreservation on immunocytochemical and neurochemical markers of monoamine...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.1993.1084

    authors： Kontur PJ,Leranth C,Redmond DE Jr,Roth RH,Robbins RJ

    更新日期：1993-06-01 00:00:00

  • Reduced dipsogenic response induced by angiotensin II activation of subfornical organ projections to the median preoptic nucleus in estrogen-treated rats.

    abstract：:The present study was carried out to investigate whether estrogen modulates the drinking response induced by activation of angiotensinergic neural pathways from the subfornical organ (SFO) to the median preoptic nucleus (MnPO). Microinjection of angiotensin II (ANG II, 10(-10) M, 0.2 microl) into the SFO elicited drin...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.2002.8054

    authors： Tanaka J,Miyakubo H,Fujisawa S,Nomura M

    更新日期：2003-01-01 00:00:00

  • Regulation of autophagy by inhibitory CSPG interactions with receptor PTPσ and its impact on plasticity and regeneration after spinal cord injury.

    abstract：:Chondroitin sulfate proteoglycans (CSPGs), extracellular matrix molecules that increase dramatically following a variety of CNS injuries or diseases, have long been known for their potent capacity to curtail cell migrations as well as axon regeneration and sprouting. The inhibition can be conferred through binding to ...

    journal_title：Experimental neurology

    pub_type： 杂志文章,评审

    doi：10.1016/j.expneurol.2020.113276

    authors： Tran AP,Warren PM,Silver J

    更新日期：2020-06-01 00:00:00

  • Functional MRI at 4.7 tesla of the rat brain during electric stimulation of forepaw, hindpaw, or tail in single- and multislice experiments.

    abstract：:Stimulation of peripheral nerves activates corresponding regions in sensorimotor cortex. We have applied functional magnetic resonance imaging (fMRI) techniques to monitor activated brain regions by means of measuring changes of blood oxygenation level-dependent contrast during electric stimulation of the forepaw, hin...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.2000.7524

    authors： Spenger C,Josephson A,Klason T,Hoehn M,Schwindt W,Ingvar M,Olson L

    更新日期：2000-12-01 00:00:00

  • Receptor protein tyrosine phosphatase σ binds to neurons in the adult mouse brain.

    abstract：:The role of type IIA receptor protein tyrosine phosphatases (RPTPs), which includes LAR, RPTPσ and RPTPδ, in the nervous system is becoming increasingly recognized. Evidence supports a significant role for these RPTPs during the development of the nervous system as well as after injury, and mutations in RPTPs are asso...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2014.02.007

    authors： Yi JH,Katagiri Y,Yu P,Lourie J,Bangayan NJ,Symes AJ,Geller HM

    更新日期：2014-05-01 00:00:00

  • Hyperbaric oxygen preconditioning attenuates hemorrhagic transformation through increasing PPARγ in hyperglycemic MCAO rats.

    abstract：:Hyperbaric oxygen preconditioning (HBO-PC) has been demonstrated to attenuate hemorrhagic transformation (HT) after middle cerebral artery occlusion (MCAO) in hyperglycemic rats. However, the mechanisms remain to be illustrated. Recently, HBO-PC has been shown to activate peroxisome proliferator-activated receptor-gam...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2014.12.016

    authors： Bian H,Hu Q,Liang X,Chen D,Li B,Tang J,Zhang JH

    更新日期：2015-03-01 00:00:00

  • Long-term injured purkinje cells are competent for terminal arbor growth, but remain unable to sustain stem axon regeneration.

    abstract：:Long-distance axon regeneration requires the activation of a specific set of neuronal growth-associated genes. Adult Purkinje cells fail to upregulate these molecules in response to axotomy and show extremely weak regenerative properties. Nevertheless, starting from several months after injury, transected Purkinje axo...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.2002.7924

    authors： Gianola S,Rossi F

    更新日期：2002-07-01 00:00:00

  • Chronic administration of quinolinic acid in the rat striatum causes spatial learning deficits in a radial arm water maze task.

    abstract：:Chronic intrastriatal administration of quinolinic acid (QA) in the rat produces a pattern of neurodegeneration similar to that seen in Huntington's disease (HD). Although these changes have been related to transient motor abnormalities, the effects of chronic QA administration on cognitive abilities have not been ass...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.1998.6767

    authors： Shear DA,Dong J,Haik-Creguer KL,Bazzett TJ,Albin RL,Dunbar GL

    更新日期：1998-04-01 00:00:00

  • The effects of ACTH and adrenocorticosteroids on seizure susceptibility in 15-day-old male rats.

    abstract：:Infantile spasms are generalized convulsive seizures seen in the first year of life. They respond poorly to conventional anticonvulsants, but are often controlled by adrenocorticotropic hormone (ACTH) therapy. Other childhood seizures are also responsive to ACTH. The present study tested the effects of ACTH and relate...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.2002.7874

    authors： Edwards HE,Vimal S,Burnham WM

    更新日期：2002-05-01 00:00:00

  • NAD+ precursor modulates post-ischemic mitochondrial fragmentation and reactive oxygen species generation via SIRT3 dependent mechanisms.

    abstract：:Global cerebral ischemia depletes brain tissue NAD+, an essential cofactor for mitochondrial and cellular metabolism, leading to bioenergetics failure and cell death. The post-ischemic NAD+ levels can be replenished by the administration of nicotinamide mononucleotide (NMN), which serves as a precursor for NAD+ synthe...

    journal_title：Experimental neurology

    pub_type： 杂志文章,评审

    doi：10.1016/j.expneurol.2019.113144

    authors： Klimova N,Fearnow A,Long A,Kristian T

    更新日期：2020-03-01 00:00:00

  • Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse.

    abstract：:Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. Th...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2017.03.002

    authors： Ye X,Shen T,Hu J,Zhang L,Zhang Y,Bao L,Cui C,Jin G,Zan K,Zhang Z,Yang X,Shi H,Zu J,Yu M,Song C,Wang Y,Qi S,Cui G

    更新日期：2017-06-01 00:00:00

  • Unity of costal and crural diaphragmatic activity in respiration.

    abstract：:In chronically implanted rats, we examined the respiratory EMG activity of the two parts of the diaphragm, costal and crural, during sleep and wakefulness. Their activity was compared and contrasted with that of the EMG activity of the cricothyroid muscle. Whether in wakefulness, while grooming and drinking, or in non...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/0014-4886(85)90051-2

    authors： Pollard MJ,Megirian D,Sherrey JH

    更新日期：1985-10-01 00:00:00

  • The life, death and regenerative ability of immature and mature rat retinal ganglion cells are influenced by their birthdate.

    abstract：:The extensive period of retinal ganglion cell (RGC) neurogenesis in the rat is associated with a protracted sequence of arrival of their axons into central targets such as the superior colliculus (SC) (Dallimore et al., 2002). Using in utero 5-bromo-2'-deoxyrudine (BrdU) injections to label early (embryonic day (E) 15...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2010.07.007

    authors： Dallimore EJ,Park KK,Pollett MA,Taylor JS,Harvey AR

    更新日期：2010-10-01 00:00:00

  • Galanin contributes to monoaminergic dysfunction and to dependent neurobehavioral comorbidities of epilepsy.

    abstract：:Status epilepticus (SE) in rats, along with chronic epilepsy, leads to the development of behavioral impairments resembling depressive disorder and/or attention deficit/hyperactivity disorder (ADHD), thus reflecting respective comorbidities in epilepsy patients. Suppressed neurotransmitter tone in the raphe nucleus (R...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2016.12.008

    authors： Medel-Matus JS,Shin D,Sankar R,Mazarati A

    更新日期：2017-03-01 00:00:00

  • Slow-wave activity homeostasis in the somatosensory cortex after spinal cord injury.

    abstract：:The cortical reorganization after spinal cord injury (SCI) involves a series of physiological changes that drive the expansion of the intact cortical area to the deafferented cortical area. These changes have always been studied under a stimulus-response paradigm, which demonstrates that the deafferented cortex become...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2019.113035

    authors： Fernández-López E,Alonso-Calviño E,Humanes-Valera D,Foffani G,Aguilar J

    更新日期：2019-12-01 00:00:00

  • Oligodendrocyte-derived J1-160/180 extracellular matrix glycoproteins are adhesive or repulsive depending on the partner cell type and time of interaction.

    abstract：:We have studied the functional involvement of J1-160 and J1-180 in the interaction between oligodendrocytes and neurons, astrocytes, or L cells in short- and long-term adhesion assays using monoclonal antibodies directed against topographically distinct epitopes on the molecules. Whereas antibodies to mouse liver memb...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/s0014-4886(05)80012-3

    authors： Morganti MC,Taylor J,Pesheva P,Schachner M

    更新日期：1990-07-01 00:00:00

  • Spatial diversity of blood-brain barrier alteration and macrophage invasion in experimental autoimmune encephalomyelitis: a comparative MRI study.

    abstract：:Inflammation plays a central role in the development of numerous disorders of the central nervous system (CNS) such as multiple sclerosis (MS). For a long time it was assumed that recruitment of macrophages into the CNS and breakdown of the blood-brain barrier (BBB) are closely linked. In the present study we challeng...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2009.08.027

    authors： Ladewig G,Jestaedt L,Misselwitz B,Solymosi L,Toyka K,Bendszus M,Stoll G

    更新日期：2009-11-01 00:00:00

  • α-Synuclein pre-formed fibrils impair tight junction protein expression without affecting cerebral endothelial cell function.

    abstract：:Recently it has been shown that there is impaired cerebral endothelial function in many chronic neurodegenerative disorders including Alzheimer's and Huntington's disease. Such problems have also been reported in Parkinson's disease, in which α-synuclein aggregation is the pathological hallmark. However, little is kno...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2016.09.003

    authors： Kuan WL,Bennett N,He X,Skepper JN,Martynyuk N,Wijeyekoon R,Moghe PV,Williams-Gray CH,Barker RA

    更新日期：2016-11-01 00:00:00

  • Synaptic evoked potentials from regenerating dorsal root axons within fetal spinal cord tissue transplants.

    abstract：:Previously injured dorsal roots were electrically stimulated to determine if regenerating sensory axons can form physiologically active synaptic contacts with neurons within fetal spinal cord tissue transplants. Dorsal rootlets, sectioned at their spinal cord entry zone, were apposed to intraspinal transplants of feta...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.1996.0101

    authors： Houle JD,Skinner RD,Garcia-Rill E,Turner KL

    更新日期：1996-06-01 00:00:00

  • γ oscillations in the human basal ganglia.

    abstract：:Interest in beta activity in the basal ganglia has mushroomed since it was first identified in the subthalamic nucleus of patients with Parkinson's disease in Jonathan Dostrovsky's landmark paper (Levy et al., 2000). Here we consider a less explored phenomenon; namely gamma frequency synchronisation of neurons in the ...

    journal_title：Experimental neurology

    pub_type： 杂志文章,评审

    doi：10.1016/j.expneurol.2012.07.005

    authors： Jenkinson N,Kühn AA,Brown P

    更新日期：2013-07-01 00:00:00

  • Local down-regulation of myelin-associated glycoprotein permits axonal sprouting with chronic nerve compression injury.

    abstract：:Chronic nerve compression (CNC) injuries induce a robust Schwann cell proliferation in a distinct spatial and temporal pattern, which is accompanied by an increase in the number of small un-myelinated axons in the area of the injury. These findings suggest that this local proliferation of Schwann cells may induce loca...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2006.02.134

    authors： Gupta R,Rummler LS,Palispis W,Truong L,Chao T,Rowshan K,Mozaffar T,Steward O

    更新日期：2006-08-01 00:00:00

  • Effect of cytosine arabinoside on the composition of the nonneuronal cell population in cerebral explants.

    abstract：:Rat cortical explants were cultured in the presence or absence of the mitotic inhibitor cytosine arabinoside to determine whether or not it affects the composition of the nonneuronal cell population within the outgrowth zone. Ultrastructural morphometric analysis of the incidence of fibroblasts, fibrous astrocytes, an...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/0014-4886(86)90092-0

    authors： Oorschot DE,Jones DG

    更新日期：1986-05-01 00:00:00

  • The need for cellular elements during axonal regeneration in the sea lamprey spinal cord.

    abstract：:Spinal axons in the larval sea lamprey regenerate following a complete spinal transection. It is not known whether regenerating growth cones require contact with cellular elements or whether the basement membrane and collagenous meninx primitiva which surround the spinal cord are sufficient for neurite out-growth. To ...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/0014-4886(91)90114-r

    authors： Lurie DI,Selzer ME

    更新日期：1991-04-01 00:00:00

  • An altered histaminergic innervation of the substantia nigra in Parkinson's disease.

    abstract：:The central histaminergic system is one of the subcortical aminergic projection systems involved in several regulatory functions. The central dopaminergic and histaminergic systems interact extensively, but little is known about the histaminergic system in diseases affecting the dopaminergic neurons. The distribution ...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.2000.7362

    authors： Anichtchik OV,Rinne JO,Kalimo H,Panula P

    更新日期：2000-05-01 00:00:00

  • Advances in nonhuman primate models of autism: Integrating neuroscience and behavior.

    abstract：:Given the prevalence and societal impact of autism spectrum disorders (ASD), there is an urgent need to develop innovative preventative strategies and treatments to reduce the alarming number of cases and improve core symptoms for afflicted individuals. Translational efforts between clinical and preclinical research a...

    journal_title：Experimental neurology

    pub_type： 杂志文章,评审

    doi：10.1016/j.expneurol.2017.07.021

    authors： Bauman MD,Schumann CM

    更新日期：2018-01-01 00:00:00

  • Immortalized neural stem cells differ from nonimmortalized cortical neurospheres and cerebellar granule cell progenitors.

    abstract：:Pluripotent neural stem cells (NSCs) have been used as replacement cells in a variety of neurological disease models. Among the many different NSCs that have been used to date, most robust results have been obtained with the immortalized neural stem cell line (C17.2) isolated from postnatal cerebellum. However, it is ...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2004.07.011

    authors： Mi R,Luo Y,Cai J,Limke TL,Rao MS,Höke A

    更新日期：2005-08-01 00:00:00

  • Fusion of neural stem cells in culture.

    abstract：:An important issue in stem cell biology relates to mechanisms of cellular plasticity. Specifically, could any observed multipotency of, e.g., adult stem cells arise from true transdifferentiation or as a result of cell-cell fusion? We studied this issue using a culture paradigm of astrocyte monolayers and multipotent ...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2005.11.016

    authors： Chen KA,Laywell ED,Marshall G,Walton N,Zheng T,Steindler DA

    更新日期：2006-03-01 00:00:00

  • Growth factors rescue embryonic dopamine neurons from programmed cell death.

    abstract：:Poor survival of embryonic dopamine neurons is a primary problem limiting the value of neurotransplantation for Parkinson's disease. Several neurotrophic factors have been shown to promote dopamine neuron survival when used individually in culture. We have found that two peptides, insulin-like growth factor-I (IGF-I) ...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.1996.0115

    authors： Zawada WM,Kirschman DL,Cohen JJ,Heidenreich KA,Freed CR

    更新日期：1996-07-01 00:00:00

  • Inspiratory muscle conditioning exercise and diaphragm gene therapy in Pompe disease: Clinical evidence of respiratory plasticity.

    abstract：:Pompe disease is an inherited disorder due to a mutation in the gene that encodes acid α-glucosidase (GAA). Children with infantile-onset Pompe disease develop progressive hypotonic weakness and cardiopulmonary insufficiency that may eventually require mechanical ventilation (MV). Our team conducted a first in human t...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2016.07.013

    authors： Smith BK,Martin AD,Lawson LA,Vernot V,Marcus J,Islam S,Shafi N,Corti M,Collins SW,Byrne BJ

    更新日期：2017-01-01 00:00:00