Abstract:
:Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly inherited neurodegenerative disorder for which no curative therapy is available. The cause of this disease is the expansion of a CAG repeat in the so-called ATXN3 gene leading to an expanded polyglutamine stretch in the ataxin-3 protein. Although the function of ataxin-3 has been defined as a deubiquitinating enzyme, the pathogenic pathway underlying SCA3 remains to be deciphered. Besides others, also the glutamatergic system seems to be altered in SCA3. The antiglutamatergic substance riluzole has thus been suggested as a potential therapeutic agent for SCA3. To assess whether riluzole is effective in the treatment of SCA3 in vivo, we used a phenotypically well-characterized conditional mouse model previously generated by us. Treatment with 10 mg/kg riluzole in the drinking water was started when mice showed impairment in rotarod performance. Post-symptomatic treatment with riluzole carried out for a period of 10 months led to reduction of the soluble ataxin-3 level and an increase in ataxin-3 positive accumulations, but did not improve motor deficits measured by rotarod. There was also no positive effect on home cage behavior or body weight. We even observed a pronounced reduction of calbindin expression in Purkinje cells in riluzole-treated mice. Thus, long-term treatment with riluzole was not able to alleviate disease symptoms observed in transgenic SCA3 mice and should be considered with caution in the treatment of human patients. Assessing riluzole as a potential treatment for spinocerebellar ataxia type 3 (SCA3) had no beneficial, but rather a worsening effect on our transgenic SCA3 mouse model. We hypothesize that: Riluzole treatment enhanced glutamate release in ATXN3-expressing cells leading to an increased Ca(2+) influx resulting in Purkinje cell damage shown by loss of calbindin expression.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Schmidt J,Schmidt T,Golla M,Lehmann L,Weber JJ,Hübener-Schmid J,Riess Odoi
10.1111/jnc.13606subject
Has Abstractpub_date
2016-07-01 00:00:00pages
150-62issue
1eissn
0022-3042issn
1471-4159journal_volume
138pub_type
杂志文章abstract::The nucleoside transporter of cerebral microvessels and choroid plexus was identified and characterized using [3H]nitrobenzylthioinosine (NBMPR) as a specific probe. [3H]NBMPR bound reversibly and with high affinity to a single specific site in particulate fractions of cerebral microvessels, choroid plexus, and cerebr...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb13098.x
更新日期:1986-12-01 00:00:00
abstract::Dopamine (DA)-producing neurons in the ventral midbrain are generated from a specified neuronal lineage and form selective axonal pathways that mediate multiple CNS functions. Expression of the gene encoding tyrosine hydroxylase (TH), which is a key enzyme of catecholamine biosynthesis, is regulated during the develop...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.00972.x
更新日期:2002-07-01 00:00:00
abstract::Exhaustive in vitro dephosphorylation of porcine neurofilaments (NFs) by alkaline or acid phosphatase did not cause a dissociation of the 210-kD (NF-H), 160-kD (NF-M), or 70-kD (NF-L) subunits and had no effect on the reassembly of NFs from urea or guanidine solution. Electron microscopy revealed that the NFs reassemb...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb04526.x
更新日期:1986-08-01 00:00:00
abstract::Neural stem cells (NSCs) play an essential role in both the developing embryonic nervous system through to adulthood where the capacity for self-renewal may be important for normal function of the CNS, such as in learning, memory and response to injury. There has been much excitement about the possibility of transplan...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.03718.x
更新日期:2006-04-01 00:00:00
abstract::G-protein coupled receptors may mediate their effects on neuronal growth and differentiation through activation of extracellular signal-regulated kinases 1/2 (ERK1/2), often elicited by transactivation of growth factor receptor tyrosine kinases. This elaborate signaling process includes inducible formation and traffic...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.07030.x
更新日期:2011-03-01 00:00:00
abstract::Dietary n-6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n-6) concentration and 20:4n-6-preferring cytosolic phospholipase A(2) (cPLA(2) -IVA) and cyclooxygenase (COX)-2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n-3) concentration and DHA-selectiv...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07597.x
更新日期:2012-03-01 00:00:00
abstract::Previous studies have supported the hypothesis that macromolecular synthesis occurs in the brain during sleep as a response to prior waking activities and that prostaglandin D2 (PGD2) is an endogenous sleep substance whose effects are dependent on adenosine A2a receptor-mediated signaling. We compared gene expression ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05257.x
更新日期:2008-05-01 00:00:00
abstract::The rat glial cell line B49 releases into its culture medium a potent neurotrophic factor that exhibits relative specificity for the dopaminergic neurons in dissociated cultures of rat embryonic midbrain. This factor is a heparin-binding, basic protein that is heterogeneously glycosylated and migrates on sodium dodecy...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.63020758.x
更新日期:1994-08-01 00:00:00
abstract::Rats were submitted to a series of 10 daily electroconvulsive shocks (ECS). A first group of animals was killed 1 day after the last seizure and a second group 30 days later. Tyrosine hydroxylase (TH) activity was measured using an in vitro assay in the nucleus caudatus, anterior cortex, amygdala, substantia nigra, ve...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb02336.x
更新日期:1990-03-01 00:00:00
abstract::Carbamylcholine stimulated phospholipase C activity in astrocytes in primary culture from the mesencephalon but not from the striatum or cerebral cortex of the mouse embryo. An alpha 1-adrenergic-mediated response was observed in all astrocyte populations. 2-Chloroadenosine potentiated the alpha 1-adrenergic response ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb02551.x
更新日期:1989-03-01 00:00:00
abstract::We are very sad that the ISN lost its President Kazuhiro Ikenaka, Professor and Chairman at National Institute for Physiological Sciences (NIPS), Director of Okazaki Institute of Integrative Biology. JNeurochem published an Obituary to value his outstanding achievements: Akio Wanaka et al. (2019) OBITUARY Kazuhiro Ike...
journal_title:Journal of neurochemistry
pub_type: 新闻
doi:10.1111/jnc.14695
更新日期:2019-06-01 00:00:00
abstract::Previous studies have demonstrated opposing roles for adenosine A1 and A2A receptors in the modulation of extracellular levels of glutamate and dopamine in the striatum. In the present study, acute systemic administration of motor-activating doses of the A2A receptor antagonist MSX-3 significantly decreased extracellu...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.02245.x
更新日期:2004-03-01 00:00:00
abstract::GM1 ganglioside binding to the crude mitochondrial fraction of rat brain and its effect on (Na+, K+)-ATPase were studied, the following results being obtained: (a) the binding process followed a biphasic kinetics with a break at 50 nM-GM1; GM1 at concentrations below the break was stably associated, while over the bre...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb00462.x
更新日期:1981-08-01 00:00:00
abstract::During development, neurons extend axons toward their appropriate synaptic targets to establish functional neuronal connections. The growth cone, a highly motile structure at the tip of the axon, is capable of recognizing extracellular guidance cues and translating them into directed axon outgrowth through modulation ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14837
更新日期:2020-02-01 00:00:00
abstract::From immunizations of mice with a glutathione S-transferase fusion protein containing residues 724-781 of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR1-flop, two monoclonal antibodies (mAbs) were developed that differed widely in their ranges of specificity. In immunocytochemical ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
abstract::Cerebral endothelial cells form the selective permeability barrier between brain and blood by virtue of their impermeable tight junctions and the presence of specific carrier systems. These specialized properties of brain capillaries are reflected in the presence of proteins that are not found in other capillaries of ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb09769.x
更新日期:1992-02-01 00:00:00
abstract::The roles of two subtypes of corticotrophin-releasing factor (CRF) receptor in corticostriatal synaptic plasticity under cocaine withdrawal condition were examined in this study. Neither the resting membrane potential and input resistance of striatal neurons nor the long-term potentiation (LTP) of corticostriatal slic...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06981.x
更新日期:2010-11-01 00:00:00
abstract::Converging lines of evidence suggest that progressive accumulation of the amyloid beta-protein (A beta) plays a central role in the genesis of Alzheimer's disease, but it was long assumed that A beta had to be assembled into extracellular amyloid fibrils to exert its cytotoxic effects. Over the past decade, data have ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2006.04426.x
更新日期:2007-06-01 00:00:00
abstract::Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well-defined. Several mechanisms have been proposed to contribute to the development of NDDs. These mechanisms may procee...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/jnc.14098
更新日期:2017-09-01 00:00:00
abstract::The in vivo biosynthesis of cholecystokinin (CCK) in subcortical regions of the rat brain was studied by intracisternal pulse injections of [35S]methionine. The rats were killed 1.0 or 1.5 h after the injection. Subcortical CCK extracted in boiling water and acetic acid was immunoabsorbed by an antiserum specific for ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1980.tb06290.x
更新日期:1980-08-01 00:00:00
abstract::Neuronal survival after ischemic injury is determined through the induction of several biological pathways. We examined whether lubeluzole, an agent efficacious in both clinical and experimental models of cerebral ischemia, modulated the signal transduction mechanisms of nitric oxide (NO), a downstream mediator of ano...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.68020710.x
更新日期:1997-02-01 00:00:00
abstract::Sphingosine-1-phosphate (S1P) is a potent biomediator that can act as either an intracellular or an intercellular messenger. In the nervous system it exerts a wide range of actions, and specific membrane receptors for it have been identified in various regions. However, the physiological origin of extracellular S1P in...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02955.x
更新日期:2005-03-01 00:00:00
abstract::The identification of a hexanucleotide repeat expansion in a non-coding region of C9orf72 as a major cause of both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) drastically changed the field of research on both of these conditions. Yet, despite the vast amount of work aimed at elucidating the m...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/jnc.13623
更新日期:2016-08-01 00:00:00
abstract::Single-bilayer vesicles of myelin are desirable for studying myelin development and metabolism. Accordingly, our interest was drawn to a procedure for vesiculating myelin (Steck et al., Biochim, Biophys. Acta 509, 397-408, 1978). We used X-ray diffraction analysis to examine these putative vesicle preparations because...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb05402.x
更新日期:1984-11-01 00:00:00
abstract::Neuroactive steroid family includes molecules synthesized in peripheral glands (i.e., hormonal steroids) and directly in the nervous system (i.e., neurosteroids) which are key regulators of the nervous function. As already reported in clinical and experimental studies, neurodegenerative diseases affect the levels of n...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12745
更新日期:2014-08-01 00:00:00
abstract::Glycerol phosphate dehydrogenase (GPDH), glucose-6-phosphate dehydrogenase (G6PDH), and lactate dehydrogenase (LDH) activities were determined in oligodendrocytes, neurons, and astrocytes isolated from the brains of developing rats. The activity of each enzyme was significantly lower in both neurons and astrocytes tha...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1982.tb08637.x
更新日期:1982-02-01 00:00:00
abstract::Neurofilament proteins (Nf) are a biomarker of disease progression in amyotrophic lateral sclerosis (ALS). This study investigated whether there are major differences in expression from in vivo measurements of neurofilament isoforms, from the light chain, NfL (68 kDa), compared with larger proteins, the medium chain (...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14542
更新日期:2018-09-01 00:00:00
abstract::The release of gamma-aminobutyric acid (GABA) was studied in slices of the head of the rabbit caudate nucleus. The slices were preincubated with [3H]GABA and then superfused. Aminooxyacetic acid was present throughout. Both the tritium in the slices and that in the superfusate consisted practically entirely of [3H]GAB...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb00624.x
更新日期:1986-04-01 00:00:00
abstract::Exposure of bovine chromaffin cells in primary culture to 0.01-1 microM reserpine caused a dose- and time-dependent increase in intracellular levels of the amidated enkephalin peptide metorphamide. Maximal levels (approximately 800% of control) were obtained at 0.1 microM reserpine and increased levels were apparent b...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb01790.x
更新日期:1986-05-01 00:00:00
abstract::The nervous tissue-specific protein B-50 (GAP-43), which has been implicated in the regulation of neurotransmitter release, is a member of a family of atypical calmodulin-binding proteins. To investigate to what extent calmodulin and the interaction between B-50 and calmodulin are involved in the mechanism of Ca(2+)-i...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.66051933.x
更新日期:1996-05-01 00:00:00