Phosphodiesterase 4B2 gene is an effector of Toll-like receptor signaling in astrocytes.


:Cyclic AMP is part of an endogenous mechanism that downregulates inflammatory response, and its intracellular concentration is regulated chiefly by cyclic nucleotide phosphodiesterases type 4. The goal of the present study was to determine whether phosphodiesterases 4 are involved in the inflammatory response of astrocytes mediated by Toll-like receptors. Astrocyte cultures established from newborn rat brain were challenged with lipoteichoic acid, a ligand of Toll-like receptor 2, polyinosinic-polycytidylic acid, a ligand of Toll-like receptor 3, or lipopolysaccharide, a ligand of Toll-like receptor 4. After 24 h the expression of genes encoding phosphodiesterase 4A, phosphodiesterase 4B and phosphodiesterase 4D was determined by real time reverse transcription polymerase chain reaction. The challenge of astrocytes with the ligands profoundly up-regulated expression of the phosphodiesterase 4B mRNA, while the phosphodiesterase 4A and 4D mRNA was either unaffected or downregulated. Moreover, Toll-like receptor ligation specifically up-regulated expression of the phosphodiesterase 4B2 transcriptional variant. Thus, polyinosinic-polycytidylic acid, lipopolysaccharide and lipoteichoic acid induced approximately 7-, 5- and 4-fold up-regulation of the message, respectively. Toll-like receptor ligation also led to an over 2-fold increase in the protein level of phosphodiesterase 4B2 as revealed by immunoblot analysis. The inactivation of Rho proteins by pretreatment with toxin B form C. difficile enhanced ligation-induced up-regulation of the phosphodiesterase 4B2 message by 4-9-fold. However, in spite of this increase in the message abundance, there was no increase in the protein level compared to cells challenged with the ligands alone. These results demonstrate that the phosphodiesterase 4B2 gene is an effector of Toll-like receptor signaling in astrocytes, and that its up-regulation at the protein level is controlled by complex mechanisms.


Metab Brain Dis


Metabolic brain disease


Borysiewicz E,Fil D,Dlaboga D,O'Donnell JM,Konat GW




Has Abstract


2009-09-01 00:00:00












  • Acute administration of methionine and/or methionine sulfoxide impairs redox status and induces apoptosis in rat cerebral cortex.

    abstract::High plasma levels of methionine (Met) and its metabolites such as methionine sulfoxide (MetO) may occur in several genetic abnormalities. Patients with hypermethioninemia can present neurological dysfunction; however, the neurotoxicity mechanisms induced by these amino acids remain unknown. The aim of the present wor...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Soares MSP,Viau CM,Saffi J,Costa MZ,da Silva TM,Oliveira PS,Azambuja JH,Barschak AG,Braganhol E,S Wyse AT,Spanevello RM,Stefanello FM

    更新日期:2017-10-01 00:00:00

  • Omega-3 fatty acids and mood stabilizers alter behavioral and oxidative stress parameters in animals subjected to fenproporex administration.

    abstract::Studies have shown that oxidative stress is involved in the pathophysiology of bipolar disorder (BD). It is suggested that omega-3 (ω3) fatty acids are fundamental to maintaining the functional integrity of the central nervous system. The animal model used in this study displayed fenproporex-induced hyperactivity, a s...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Gomes LM,Carvalho-Silva M,Teixeira LJ,Rebelo J,Mota IT,Bilesimo R,Michels M,Arent CO,Mariot E,Dal-Pizzol F,Scaini G,Quevedo J,Streck EL

    更新日期:2017-04-01 00:00:00

  • Influence of BDNF polymorphisms on Wilson's disease susceptibility and clinical course.

    abstract::Susceptibility to Wilson's disease (WD) and its clinical manifestations are thought to be affected by genetic factors, including polymorphisms. The role of brain-derived neurotrophic factor (BDNF) in the pathogenesis of neurodegenerative diseases is now widely discussed. The aim of the present study was to evaluate th...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Mirowska-Guzel D,Litwin T,Gromadzka G,Czlonkowski A,Czlonkowska A

    更新日期:2013-09-01 00:00:00

  • Tissue kallikrein and kinin receptor expression in an angiogenic co-culture neuroblastoma model.

    abstract::The sprouting of new blood vessels from pre-existing vasculature (angiogenesis) is essential for tumour survival, influenced by tumour cell-endothelial cell interactions and is tightly regulated by biochemical cues including the kallikrein-kinin system (KKS). We examined the structural interaction between neuroblastom...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Naidoo S,Raidoo DM

    更新日期:2006-09-01 00:00:00

  • The neuroprotective effect of betanin in trimethyltin-induced neurodegeneration in mice.

    abstract::Betanin, a natural food colorant with powerful antioxidative properties, has not been studied in terms of neurodegenerative disease intervention. Therefore, the present study aimed to investigate the neuroprotective effects of betanin against trimethyltin chloride (TMT) -induced neurodegeneration in mice. Forty male I...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Thong-Asa W,Prasartsri S,Klomkleaw N,Thongwan N

    更新日期:2020-12-01 00:00:00

  • Changes in regional brain volumes in social anxiety disorder following 12 weeks of treatment with escitalopram.

    abstract::It has been suggested that antidepressants, including the selective serotonin reuptake inhibitors have neurotrophic effects. Nevertheless, the impact of treatment with a selective serotonin re-uptake inhibitor on regional brain volumes in social anxiety disorder has not been studied. 11 subjects with social anxiety di...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Cassimjee N,Fouche JP,Burnett M,Lochner C,Warwick J,Dupont P,Stein DJ,Cloete KJ,Carey PD

    更新日期:2010-12-01 00:00:00

  • Proline dehydrogenase gene (PRODH) polymorphisms and schizophrenia susceptibility: a meta-analysis.

    abstract::Previous studies have been conducted to explore the association between proline dehydrogenase gene (PRODH) polymorphisms and schizophrenia (SZ) susceptibility, but providing the controversial results. Here we performed this meta-analysis to determine whether PRODH variants were associated with SZ risk. Relevant studie...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章,meta分析


    authors: Guo X,Tang P,Yang C,Li R

    更新日期:2018-02-01 00:00:00

  • Neuroprotective effect of Crocus sativus against cerebral ischemia in rats.

    abstract::The present study aimed to investigate the role of vascular endothelial growth factor (VEGF) in the neuroprotective effect of Crocus sativus (saffron) against cerebral ischemia/reperfusion injury (I/R) in rats. Four groups of a total forty I/R rats with 60-min occlusion followed by 48 h reperfusion or sham surgery wer...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Abdel-Rahman RF,El Awdan SA,Hegazy RR,Mansour DF,Ogaly HA,Abdelbaset M

    更新日期:2020-03-01 00:00:00

  • Rivastigmine reverses cognitive deficit and acetylcholinesterase activity induced by ketamine in an animal model of schizophrenia.

    abstract::Schizophrenia is one of the most disabling mental disorders that affects up to 1 % of the population worldwide. Although the causes of this disorder remain unknown, it has been extensively characterized by a broad range of emotional, ideational and cognitive impairments. Studies indicate that schizophrenia affects neu...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Zugno AI,Julião RF,Budni J,Volpato AM,Fraga DB,Pacheco FD,Deroza PF,Luca RD,de Oliveira MB,Heylmann AS,Quevedo J

    更新日期:2013-09-01 00:00:00

  • Increased brain concentrations of endogenous (non-benzodiazepine) GABA-A receptor ligands in human hepatic encephalopathy.

    abstract::It has been suggested that alterations of GABAergic neurotransmission are implicated in the pathophysiology of hepatic encephalopathy (HE). Increased concentrations of endogenous benzodiazepines with positive allosteric modulatory properties at the GABA-A receptor complex were proposed as a pathophysiological mechanis...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Ahboucha S,Pomier-Layrargues G,Butterworth RF

    更新日期:2004-12-01 00:00:00

  • Anxiolytic-like effects of α-asarone in a mouse model of chronic pain.

    abstract::α-asarone (ASR) is a major bioactive compound isolated from the rhizome of Acorus tatarinowii Schott and it has extensive biological effects. Clinically, anxiety disorder is a common comorbidity of chronic pain. However, limited information is available regarding the effects of ASR on chronic pain-related anxiety. Thi...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Tian J,Tian Z,Qin SL,Zhao PY,Jiang X,Tian Z

    更新日期:2017-12-01 00:00:00

  • A patient with mitochondrial disorder due to a novel mutation in MRPS22.

    abstract::MRPS22 gene defect is a very rare newly discovered mitochondrial disorder. We report a 4-month-old severely affected male infant with MRPS22 mutation. Whole exome sequencing revealed a novel homozygous splicing mutation c.339 + 5 G > A in MRPS22 gene. He has mild dysmorphism, hypotonia, developmental delay but not hyp...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Kılıç M,Oğuz KK,Kılıç E,Yüksel D,Demirci H,Sağıroğlu MŞ,Yücel-Yılmaz D,Özgül RK

    更新日期:2017-10-01 00:00:00

  • Wilson disease.

    abstract::Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism, resulting in pathological accumulation of copper in many organs and tissues. The hallmarks of the disease are the presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings. The leading neurologic symptoms in...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章,评审


    authors: Kitzberger R,Madl C,Ferenci P

    更新日期:2005-12-01 00:00:00

  • Prolactin, flupenthixol decanoate and first episode schizophrenia - clinical and laboratory correlates.

    abstract::First-episode psychosis (FEP) patients are more sensitive to neuroleptic side-effects such as hyperprolactinemia. We examined the prolactin levels of previously minimally treated patients with first episode schizophrenia over their first year of treatment with flupenthixol decanoate and the relationship between prolac...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Retief M,Chiliza B,Phahladira L,Emsley R,Asmal L

    更新日期:2019-12-01 00:00:00

  • The role of adenosine receptor agonist and antagonist on Hippocampal MDMA detrimental effects; a structural and behavioral study.

    abstract::There is abundant evidence showing that repeated use of MDMA (3, 4-Methylenedioxymethamphetamine, ecstasy) has been associated with depression, anxiety and deficits in learning and memory, suggesting detrimental effects on hippocampus. Adenosine is an endogenous purine nucleoside that has a neuromodulatory role in the...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Kermanian F,Mehdizadeh M,Soleimani M,Ebrahimzadeh Bideskan AR,Asadi-Shekaari M,Kheradmand H,Haghir H

    更新日期:2012-12-01 00:00:00

  • Neuroprotective effects of Nigella sativa extract upon the hippocampus in PTU-induced hypothyroidism juvenile rats: A stereological study.

    abstract::This study aimed to examine the neuroprotective effects of Nigella sativa (N. sativa) in the hippocampus of propylthiouracil (PTU)-induced hypothyroid rats during neonatal and juvenile growth. Twenty- five pregnant rats from early gestation (GD 0) were divided into five groups: (1) control (received drinking water), (...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Asiaei F,Fazel A,Rajabzadeh AA,Hosseini M,Beheshti F,Seghatoleslam M

    更新日期:2017-10-01 00:00:00

  • Cognitive impairment is correlated with insulin resistance degree: the "PA-NICO-study".

    abstract::Several epidemiological studies have shown that Diabetes Mellitus (DM) or Insulin Resistance (IR) increases the risk of dementia. Besides, some authors suggested that poor glucose control to be associated with worse cognitive function. We aimed to assess cognitive functions and IR-degree over time in diabetic. We also...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Fava A,Colica C,Plastino M,Messina D,Cristiano D,Opipari C,Vaccaro A,Gorgone G,Bosco F,Fratto A,De Bartolo M,Bosco D

    更新日期:2017-06-01 00:00:00

  • The role of the MAP-kinase superfamily in beta-amyloid toxicity.

    abstract::The mitogen-activated protein kinase (MAP kinase) pathway participates in a number of reactions of the cell when responding to various external stimuli. These stimuli include growth factor binding to its receptor as well as stressful situations such as hypoxia and oxidative stress. It has been postulated that one of t...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Daniels WM,Hendricks J,Salie R,Taljaard JJ

    更新日期:2001-12-01 00:00:00

  • Normal diet Vs High fat diet - A comparative study: Behavioral and neuroimmunological changes in adolescent male mice.

    abstract::Recent evidence has established that consumption of High-fat diet (HFD)-induced obesity is associated with deficits in hippocampus-dependent memory/learning and mood states. Nevertheless the link between obesity and emotional disorders still remains to be elucidated. This issue is of particular interest during adolesc...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Wu H,Liu Q,Kalavagunta PK,Huang Q,Lv W,An X,Chen H,Wang T,Heriniaina RM,Qiao T,Shang J

    更新日期:2018-02-01 00:00:00

  • Metabolic changes in axotomized fetal and early postnatal hamster facial motoneurons: an autoradiographic study.

    abstract::The developing facial neurons of a series of hamsters ranging in age from the 14-day fetus to the 9 day postnatal were axotomized. Postoperative times were graded for each age so that the retrograde response could be observed before any significant amount of cell degeneration or death occurred. The incorporation of tr...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Clark P,Jones KJ,LaVelle A

    更新日期:1993-06-01 00:00:00

  • Nonlinear determination of Michaelis-Menten kinetics with model evaluation through estimation of uncertainties.

    abstract::A structured analytic approach was developed to evaluate enzyme kinetic parameters using non-linear least-squares fitting. The approach was implemented in a software package called KinSim and designed to run on Windows 95, 98, and NT platforms. The software and the theoretical approach were tested using kinetic data o...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Mason GF,Lai JC

    更新日期:2000-06-01 00:00:00

  • SB203580 reverses memory deficits and depression-like behavior induced by microinjection of Aβ1-42 into hippocampus of mice.

    abstract::A high co-morbidity between Alzheimer's disease (AD) and depression suggests there might be similar mechanisms underlying the course of these diseases. Previous studies have shown that p38MAPK plays a critical role in the pathophysiology of AD and depression. However, little is known about whether SB203580, a selectiv...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Guo J,Chang L,Li C,Li M,Yan P,Guo Z,Wang C,Zha Q,Wang Q

    更新日期:2017-02-01 00:00:00

  • Severe infantile epileptic encephalopathy associated with D-glyceric aciduria: report of a novel case and review.

    abstract::D-glycerate 2 kinase (DGK) is an enzyme that mediates the conversion of D-glycerate, an intermediate metabolite of serine and fructose metabolism, to 2-phosphoglycerate. Deficiency of DGK leads to accumulation of D-glycerate in various tissues and its massive excretion in urine. D-glyceric aciduria (DGA) is an autosom...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章,评审


    authors: Zehavi Y,Mandel H,Eran A,Ravid S,Abu Rashid M,Jansen EEW,Wamelink MMC,Saada A,Shaag A,Elpeleg O,Spiegel R

    更新日期:2019-04-01 00:00:00

  • Lignans from Schisandra chinensis ameliorate cognition deficits and attenuate brain oxidative damage induced by D-galactose in rats.

    abstract::The aim of this study was to explore the neuroprotective effects of active compounds from Schisandra chinensis (Trucz.) Baill. (Magnoliaceae) against the D-galactose (D-gal)-induced neurotoxicity in rat. The Wistar rats were subcutaneously injected with D-gal (150 mg/(kg day)) for six weeks and orally administered wit...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Yan T,Shang L,Wang M,Zhang C,Zhao X,Bi K,Jia Y

    更新日期:2016-06-01 00:00:00

  • Impaired lipid metabolism markers to assess the risk of neuroinflammation in autism spectrum disorder.

    abstract::Autism spectrum disorder (ASD) is a multifactorial disorder caused by an interaction between environmental risk factors and a genetic background. It is characterized by impairment in communication, social interaction, repetitive behavior, and sensory processing. The etiology of ASD is still not fully understood, and t...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Qasem H,Al-Ayadhi L,Bjørklund G,Chirumbolo S,El-Ansary A

    更新日期:2018-08-01 00:00:00

  • Neuro- and nephrotoxicity of subchronic cadmium chloride exposure and the potential chemoprotective effects of selenium nanoparticles.

    abstract::Cadmium (Cd) exposure leads to production of reactive oxygen species (ROS), which are associated with Cd-induced neurotoxicity and nephrotoxicity. Selenium nanoparticles (Se-NPs) have high bioavailability and antioxidant activities so it attracted wide spread attention. The present study examined the possible ameliora...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Sadek KM,Lebda MA,Abouzed TK,Nasr SM,Shoukry M

    更新日期:2017-10-01 00:00:00

  • Dietary supplementation of undernourished rats with soy or safflower oil: effects on myelin polyunsaturated fatty acids.

    abstract::Undernourished suckling rats were administered, by gastric intubation, either soy oil (which is rich in both linoleic and linolenic acids) or safflower oil (which is rich in linoleic acid but deficient in linolenic acid) to determine (1) if dietary supplementation would offset the hypomyelination characteristic of the...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Divakaran P,Pavlina T,Johnson RC,Cotter R,Madsen D,Wiggins R

    更新日期:1986-06-01 00:00:00

  • Novel mutations and clinical outcomes of copper-histidine therapy in Menkes disease patients.

    abstract::Menkes disease is a very rare X-linked copper metabolism disorder that results from an ATP7A gene mutation. With the advent of subcutaneous copper-histidine therapy, the early diagnosis of Menkes disease becomes of utmost importance for patients' prognosis. In the present study, the clinical characteristics of 12 Kore...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Kim JH,Lee BH,Kim YM,Choi JH,Kim GH,Cheon CK,Yoo HW

    更新日期:2015-02-01 00:00:00

  • Regional metabolic status of the E-18 rat fetal brain following transient hypoxia/ischemia.

    abstract::Increasing evidence indicates that fetal metabolic stress may result in a variety of post-natal perturbations during brain development. The goal of the study was to determine the duration of hypoxia/ischemia that would elicit a demonstrable regional depression of metabolism in the fetal brain and further to examine se...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Pundik S,Robinson S,Lust WD,Zechel J,Buczek M,Selman WR

    更新日期:2006-12-01 00:00:00

  • Glutamate receptors in alcohol withdrawal-induced neurotoxicity.

    abstract::Chronic ethanol ingestion results in an "up-regulation" of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in mouse brain. This increase in receptors is associated with ethanol withdrawal seizures, which can be attenuated by NMDA receptor antagonists. Chronic exposure to ethanol (3 days) of rat cerebella...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章


    authors: Hoffman PL

    更新日期:1995-03-01 00:00:00