Abstract：
:Metformin is the most frequently used drug for the treatment of type 2 diabetes in humans. However, only little is known about effects of metformin on brain metabolism. To investigate potential metabolic consequences of an exposure of brain cells to metformin, we incubated rat astrocyte-rich primary cultures with this compound. Metformin in concentrations of up to 30 mM did not acutely compromise the viability of astrocytes, but caused a time- and concentration-dependent increase in cellular glucose consumption and lactate production. For acute incubations in the hour range, the presence of 10 mM metformin doubled the glycolytic flux, while already 1 mM metformin doubled glycolytic flux during incubation for 24 h. In addition to metformin, also other guanidino compounds increased astrocytic lactate production. After 4 h of incubation, half-maximal stimulation of glycolysis was observed for metformin, guanidine and phenformin at concentrations of around 3 mM, 3 mM and 30 µM, respectively. The acute stimulation of glycolytic lactate production by metformin was persistent after removal of extracellular metformin and was also observed, if glucose was absent from the incubation medium or replaced by other hexoses. The metformin-induced stimulation of glycolytic flux was not prevented by compound C, an inhibitor of AMP-dependent protein kinase, nor was it additive to the stimulation of glycolytic flux caused by respiratory chain inhibitors. These data demonstrate that the antidiabetic drug metformin has the potential to strongly activate glycolytic lactate production in brain astrocytes.
journal_name
Neurochem Resjournal_title
Neurochemical researchauthors
Westhaus A,Blumrich EM,Dringen Rdoi
10.1007/s11064-015-1733-8subject
Has Abstractpub_date
2017-01-01 00:00:00pages
294-305issue
1eissn
0364-3190issn
1573-6903pii
10.1007/s11064-015-1733-8journal_volume
42pub_type
杂志文章abstract：:Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory and immune modulating lipid mediators involved in inflammatory diseases and were boosted in human brain after acute phase of cerebral ischemia. The antagonism of CysLTs receptors may offer protection against ischemic damage. Therefore it seemed interesting to...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-014-1478-9
更新日期：2015-01-01 00:00:00
abstract：:The present study addressed the hypothesis that the DA transporter ligand, [3H]mazindol, labels multiple sites/states associated with the dopamine (DA) transporter in striatal membranes. Incubations with [3H]mazindol proceeded for 18-24 hr at 4 degrees C in 55.2 mM sodium phosphate buffer, pH 7.4, with a protease inhi...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00966817
更新日期：1994-02-01 00:00:00
abstract：:The human formyl peptide receptor like 1 (FPRL-1) is a variant of the Gi-coupled formyl-peptide receptor. Functional FPRL-1 is endogenously expressed in the U87 astrocytoma cell line and there is accumulating evidence to suggest that FPRL-1 may be involved in neuroinflammation associated with the pathogenesis of Alzhe...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-007-9425-7
更新日期：2008-01-01 00:00:00
abstract：:We investigated the effects of H(2)O(2)-induced oxidative stress on the delayed-rectifier current (IK(DR)), neuronal physiological and morphological properties. Measurements were obtained from hippocampal CA1 neurons in control solution and from the same neurons after exposure to oxidative stress (short- and long-term...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-007-9287-z
更新日期：2007-07-01 00:00:00
abstract：:Planarians are rapidly developing into very useful research subjects in pharmacology and neuroscience research. Here we report that curare, a cholinergic nicotinic receptor antagonist, alleviates the nicotine-induced planarian seizure-like movements (pSLM) by up to 50 % at equimolar concentrations of nicotine and cura...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-015-1512-6
更新日期：2015-10-01 00:00:00
abstract：:Hippocampal cells dissociated from 5-day-old rat pups were grown in a suitable chemically defined basal medium, supplemented or not with 3,3',5-triiodo-L-thyronine (T3), [Arg8]-vasopressin (AVP), or both, at different concentrations. Four days after plating, neuron-like cells began to degenerate drastically in the bas...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00965924
更新日期：1989-10-01 00:00:00
abstract：:Protein kinase C has recently attracted considerable attention because of its importance in the control of cell division, cell differentiation, and signal transduction across the cell membrane. The activity of this enzyme is altered by several lipids such as diacylglycerol, free fatty acids, lipoxins, gangliosides, an...
journal_title：Neurochemical research
pub_type： 杂志文章,评审
doi：10.1007/BF00973288
更新日期：1988-06-01 00:00:00
abstract：:Lesions of the nigrostriatal pathway are known to induce a compensatory up-regulation of various neurotrophic factors. In this study we examined protein content of basic fibroblast growth factor (FGF-2) in tissue samples taken from the ventral midbrain and striatum at two different time points following a neurotoxic l...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-009-0093-7
更新日期：2010-04-01 00:00:00
abstract：:2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) was phosphorylated in vivo, in brain slices and in a cell free system. Phosphoamino acid analysis of immunoprecipitated CNP labeled in vivo and in brain slices revealed phosphorylation of phosphoserine (94%) and phosphothreonine (5%) residues. Phosphorylation of CNP in...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00967712
更新日期：1994-06-01 00:00:00
abstract：:Acute tryptophan depletion (ATD) is extensively used to investigate the role of central serotonin (5-HT). However, several studies reported that ATD had no significant effect on central 5-HT concentration and some ATD-induced changes was independent of 5-HT in the rodent brain. Therefore, the potential mechanism of AT...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-013-1177-y
更新日期：2013-12-01 00:00:00
abstract：:The activity, properties, and developmental pattern of cysteine sulfinate transaminase (CSA-T) were studied in chick retina and compared with the activity, properties, and developmental pattern of glutamate oxaloacetate transaminase (GOT). Their optimum pH is identical whereas the effect of pyridoxal phosphate seems t...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00964358
更新日期：1978-02-01 00:00:00
abstract：:A study was undertaken in rats to evaluate the effects of short-term oral ethanol administration on the levels of fatty acid ethyl esters (FAEE) in brain and peripheral organs in the presence and absence of pretreatment with L-carnitine. Administration of ethanol to rats for seven days resulted in fatty acid ethyl est...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1023/a:1020984114824
更新日期：1999-01-01 00:00:00
abstract：:The effect of 4-aminopyridine on [3H]acetylcholine release was studied in rat cerebral cortical synaptosomes in the presence of a several secretagogues that have different mechanisms of action. As found previously, 4-aminopyridine increased [3H]acetylcholine release in a concentration-dependent manner (5-10 mM); a hig...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00969632
更新日期：1989-02-01 00:00:00
abstract：:Ménière's disease (MD) is characterized by the triad of fluctuating hearing loss, episodic vertigo and tinnitus, and by endolymphatic hydrops found on post-mortem examination. Increasing evidence suggests that oxidative stress is involved in the development of endolymphatic hydrops and that cellular damage and apoptot...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-010-0304-2
更新日期：2010-12-01 00:00:00
abstract：:Oxidative stress-induced neuronal cell death requires opening of the mitochondrial permeability transition pore. P53 mitochondrial translocation and association with Cyclophilin D (Cyp-D) is required for the pore opening. Here we tested this signaling axis in oxygen glucose deprivation (OGD)/re-oxygenation-induced in ...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-013-0968-5
更新日期：2013-04-01 00:00:00
abstract：:Microdissection of selected regions of central nervous system (CNS) has provided the basis of modern chemoarchitectonics. Laser microdissection is a modern variant of the "Palkovits punch" technique and used together with gene array analysis has revolutionalized CNS molecular analysis. Here we describe the use of such...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-005-9008-4
更新日期：2006-02-01 00:00:00
abstract：:Guanine nucleotides (GN) have been implicated in many intracellular mechanisms. Extracellular actions, probably as glutamate receptor antagonists, have also been recently attributed to these compounds. GN may have a neuroprotective role by inhibiting excitotoxic events evoked by glutamate. Effects of extracellular GN ...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1023/a:1007557600687
更新日期：2000-02-01 00:00:00
abstract：:To assess RNAi mediated inhibition of the expression of wt-DYT1 on H(2)O(2)-induced toxicity in NIH 3T3 cells and primary cortical neurons. To detect the function of wild-type Torsin A and the effect of SiRNA on the wt-DYT1 gene. The shRNA expression vector was constructed by ligating annealed complementary shRNA olig...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-010-0177-4
更新日期：2010-08-01 00:00:00
abstract：:Protein kinase A (PKA) plays a crucial role in tau hyperphosphorylation, an early event of Alzheimer disease (AD), and 17beta-estradiol replacement in aging women forestalls the onset of AD. However, the role of estradiol in PKA-induced tau hyperphosphorylation is not known. Here, we investigated the effect of 17beta-...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-008-9638-4
更新日期：2008-09-01 00:00:00
abstract：:We have previously shown that 5-methyltetrahydrofolate influences neuro-secretion. The present study more precisely characterises the processes involved and considers one probable site of action. Focusing on the tyrosine-noradrenalin axis in cerebellum we showed 5-methyltetrahydrofolate causes a significant reduction ...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF01705542
更新日期：1995-06-01 00:00:00
abstract：:In this report data are summarized on changes in the quantity of proteolipid protein (PLP), its amino acid composition, and the lipid moiety of these lipid-protein complexes in rat brain during postnatal development. In all three parts of the central nervous system (CNS) studied (cerebral hemispheres, medulla oblongat...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:Mevalonate phosphorylation was studied in neonatal chick brain. Formation of phosphorylated derivatives of mevalonic acid increased with the pH in the range assays (5.5-9.5). Phosphomevalonate kinase was completely inactivated after treatment at 50 degree C for 5-10 min, whereas mevalonate kinase was found to retain i...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00965047
更新日期：1981-08-01 00:00:00
abstract：:Nicotine has been reported to exert certain protective effect in the Parkinson's and Alzheimer's diseases. Whether it has a similar action in focal cerebral ischemia was unclear. In the present study, rats received either an injection of (-)-nicotine hydrogen tartrate salt (1.2 mg/kg, i.p.) or the vehicle 2 h before t...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-012-0927-6
更新日期：2013-02-01 00:00:00
abstract：:The lysosomal degradation of several sphingolipids requires the presence of four small glycoproteins called saposins, generated by proteolytic processing of a common precursor, prosaposin. Saposins share several structural properties, including six similarly located cysteines forming three disulfide bridges with the s...
journal_title：Neurochemical research
pub_type： 杂志文章,评审
doi：10.1023/a:1022530508763
更新日期：1999-02-01 00:00:00
abstract：:The mutual interactions and the effects of GABA on the saturable transport components of taurine and hypotaurine were investigated with mouse brain slices. The low-affinity taurine transport was competitively inhibited by both hypotaurine and GABA. Hypotaurine did not alter the kinetic parameters of high-affinity taur...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00964995
更新日期：1983-11-01 00:00:00
abstract：:Neuroglycan C (NGC) is a transmembrane-type chondroitin sulfate proteoglycan that promotes neurite outgrowth. To identify the ligand of NGC, we applied a detergent-solubilized membrane fraction of fetal rat brains to an NGC-immobilized affinity column. Several proteins were eluted from the column including an 18 kDa-b...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-010-0164-9
更新日期：2010-08-01 00:00:00
abstract：:Repeated electroconvulsive shock is an effective treatment for affective disorders. Striatum, hippocampus and brainstem are involved in affective disorders. Sodium-potassium/ATPase is of paramount importance for the proper functioning of the brain and its involvement in the affective disorders has been claimed for a l...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-006-9046-6
更新日期：2006-04-01 00:00:00
abstract：:Three peptides overlapping the tryptophan region of bovine CNS myelin basic protein were synthesized by the solid phase procedure of Merrifield. These were the nonapeptide H-Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys-OH, the octapeptide H-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys-OH, and the heptapeptide H-Trp-Gly-Ala-Glu-Gly-Gln-Lys-...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00964458
更新日期：1980-01-01 00:00:00
abstract：:The real time dynamics of K+ evoked neurosecretion in cerebellar slices has been monitored electrochemically. In the presence of 5-methyltetrahydrofolate a statistically significant diminution in secretory response occurs. Agonists to probe the pharmacological basis for this indicate it is not due to voltage sensitive...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00966940
更新日期：1993-05-01 00:00:00
abstract：:ESR spin trapping technique was used to detect and analyze free radical formation. When 6-hydroxydopamine (6-OHDA) was incubated alone or in the presence of a free radical generating system (H2O2 and FeSO4), hydroxyl free radicals were observed in a concentration-dependent manner. Glutathione was found to be the most ...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00965833
更新日期：1991-01-01 00:00:00
