Abstract:
:We have previously demonstrated hippocampal hyperglutamatergic signaling occurs prior to plaque accumulation in AβPP/PS1 mice. Here, we evaluate 2-Amino-6-(trifluoromethoxy) benzothiazole (riluzole) as an early intervention strategy for Alzheimer's disease (AD), aimed at restoring glutamate neurotransmission prior to substantial Beta amyloid (Aβ) plaque accumulation and cognitive decline. Male AβPP/PS1 mice, a model of progressive cerebral amyloidosis, were treated with riluzole from 2-6 months of age. Morris water maze, in vivo electrochemistry, and immunofluorescence were performed to assess cognition, glutamatergic neurotransmission, and pathology, respectively, at 12 months. Four months of prodromal riluzole treatment in AβPP/PS1 mice resulted in long-lasting procognitive effects and attenuated glutamatergic tone that was observed six months after discontinuing riluzole treatment. Riluzole-treated AβPP/PS1 mice had significant improvement in long-term memory compared to vehicle-treated AβPP/PS1 mice that was similar to normal aging C57BL/6J control mice. Furthermore, basal glutamate concentration and evoked-glutamate release levels, which were elevated in vehicle-treated AβPP/PS1 mice, were restored to levels observed in age-matched C57BL/6J mice in AβPP/PS1 mice receiving prodromal riluzole treatment. Aβ plaque accumulation was not altered with riluzole treatment. This study supports that interventions targeting the glutamatergic system during the early stages of AD progression have long-term effects on disease outcome, and importantly may prevent cognitive decline. Our observations provide preclinical support for targeting glutamate neurotransmission in patients at risk for developing AD.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Hascup KN,Findley CA,Britz J,Esperant-Hilaire N,Broderick SO,Delfino K,Tischkau S,Bartke A,Hascup ERdoi
10.1111/jnc.15224subject
Has Abstractpub_date
2020-10-26 00:00:00eissn
0022-3042issn
1471-4159pub_type
杂志文章abstract::We recently reported that by postnatal day 40 the activity of sn-glycerol-3-phosphate dehydrogenase (GPDH) was significantly depressed in the cerebellum of genetic-hypothyroid mutant mice. This mutant mouse-GPDH combination was used in the present study to define the critical time period during which thyroid hormone (...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb10087.x
更新日期:1992-12-01 00:00:00
abstract::Although isoelectric focusing has been used to demonstrate the presence of oligoclonal IgG in the CSF, the technique has not allowed detection of oligoclonal IgG in unconcentrated CSF. A new technique is reported, by which unconcentrated CSF is separated by isoelectric focusing, and the IgG bands are then detected by ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb00445.x
更新日期:1981-05-01 00:00:00
abstract::Primary neuronal cultures from 8-day-old rat cerebellum were incubated in the presence of exogenously added 16 nM [gamma-32P]ATP. Phosphorylation of a 45-kDa endogenous protein was detected within 1 min and increased linearly for approximately 20 min. Unlike what was seen with [gamma-32P]ATP, in the presence of [32P]o...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.63062028.x
更新日期:1994-12-01 00:00:00
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::This paper describes the interaction of neurotensin with mouse neuroblastoma N1E115 cells. Neurotensin binding sites are undetectable in nondifferentiated neuroblastoma cells. They appear during cell differentiation in the presence of a low serum concentration and dimethyl sulfoxide, and reach a maximal level after 50...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb12715.x
更新日期:1984-04-01 00:00:00
abstract::pros-Methylimidazoleacetic acid (p-MIAA; 1-methylimidazole-5-acetic acid), an isomer of the histamine metabolite, tele-methylimidazoleacetic acid (t-MIAA), is present in brain and CSF. Its relationship to histamine synthesis and catabolism was assessed in brains of rats. p-MIAA distribution in brain regions was hetero...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb09156.x
更新日期:1989-02-01 00:00:00
abstract::Mutations in the free radical-scavenging enzyme copper/zinc superoxide dismutase (Cu/Zn-SOD) are associated with neuronal death in humans and mice. Here, we examine the effects of human wild-type (WT SOD) and mutant (Gly93 --> Ala; G93A) Cu/Zn-SOD enzyme on the fate of postnatal midbrain neurons. One-week-old cultures...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.69010021.x
更新日期:1997-07-01 00:00:00
abstract::Protein aggregation into amyloid fibrils is a key feature of a multitude of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Prion disease. To detect amyloid fibrils, fluorophores with high sensitivity and better efficiency coupled with the low toxicity are in high demand even to date. In this pursuit,...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.15138
更新日期:2020-08-04 00:00:00
abstract::2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental pollutant that could induce significant toxic effects in the human nervous system. However, the underlying molecular mechanism has not been entirely elucidated. Reactive astrogliosis has implicated in various neurological diseases via the product...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12696
更新日期:2014-06-01 00:00:00
abstract::The distribution of cerebellar gangliosides was studied in staggerer (sg/sg) mutant mice, where the majority of granule cells die after completing their migration across the molecular layer. In addition, the external granule cell layer in sg/sg mice persists longer than in normal mice. Moreover, in the sg/sg cerebellu...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb12856.x
更新日期:1984-10-01 00:00:00
abstract::The glutamine cycle has been proposed as a pathway in which glutamine synthesized in glia provides substrate for synthesis of the neurotransmitters glutamate and GABA as they are lost from neurons. To test whether GABA may regulate this pathway, the effect of elevated GABA on the glial enzyme glutamine synthetase was ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.65010355.x
更新日期:1995-07-01 00:00:00
abstract::Neuronal death due to excessive activation of N-methyl-d-aspartate (NMDA) receptors is a hallmark of neurodegenerative diseases. The polyamines: putrescine, spermine, and spermidine, bind to specific sites on the NMDA receptor and promote its activation, but their role in NMDA-induced neuronal death is ill defined. In...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04843.x
更新日期:2007-11-01 00:00:00
abstract::Action mechanism of lipopolysaccharide (LPS), interleukin-1β (IL-1β), and lysophosphatidic acid (LPA) to regulate motility, an important process of astrogliosis, was investigated in rat astrocytes. While LPA exerted no significant effect on the cell migration, the prior treatment of the cells with LPS or IL-1β resulte...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07188.x
更新日期:2011-04-01 00:00:00
abstract::The binding of L-2-[3H]amino-4-phosphonobutyrate ([3H]L-AP4) was examined in brain sections of wild-type mice and mice lacking the mGluR4 subtype of metabotropic glutamate receptors (mGluRs). Very high relative densities of [3H]L-AP4 binding were observed in the molecular layer of the cerebellar cortex, the nucleus ba...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0720835.x
更新日期:1999-02-01 00:00:00
abstract::Excitotoxicity mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors has been proposed to play a major role in the selective death of motor neurons in sporadic amyotrophic lateral sclerosis (ALS), and motor neurons are more vulnerable to AMPA receptor-mediated excitotoxicity than are o...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.03903.x
更新日期:2006-08-01 00:00:00
abstract::As an initial step to study the function of the gene encoding the human neuropeptide FF (NPFF), we cloned a 4.7-kb sequence from the promoter region. Primer extension and 5'-rapid amplification of cDNA ends revealed multiple transcription initiation sites. Northern blot analysis of the mRNA expression revealed a speci...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.01035.x
更新日期:2002-09-01 00:00:00
abstract::Mutations in copper/zinc superoxide dismutase (SOD1) account for 10-20% of a familial form of amyotrophic lateral sclerosis (ALS). A common feature of SOD1 mutants is abnormal aggregation of the aberrant SOD1 in neurons and glia. We now report that in ALS transgenic mouse models the constitutively expressed heat shock...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03054.x
更新日期:2005-05-01 00:00:00
abstract::Choline acetyltransferase (ChAT) is a specific phenotypic marker of cholinergic neurons. Previous reports showed that different upstream regions of the ChAT gene are necessary for cell type-specific expression of reporter genes in cholinergic cell lines. The identity of the mouse ChAT promoter region controlling the e...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0720017.x
更新日期:1999-01-01 00:00:00
abstract::The metabolic pathway of inositol phospholipids represents a series of synthetic and hydrolytic reactions with inositol as a by-product. Hence, the rate of [3H]inositol release from prelabeled phospholipids can be used as a reflection of activity of this pathway. In the frog sympathetic ganglion prelabeled with [3H]in...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb02524.x
更新日期:1989-03-01 00:00:00
abstract::According to the amyloid hypothesis, accumulation of amyloid beta-peptide (A beta) in the brain is the primary pathogenic event in Alzheimer's disease (AD). Recent evidence indicates that A beta within the intravascular space is linked to A beta deposited in the brain suggesting that transport of A beta between the br...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2004.02385.x
更新日期:2004-05-01 00:00:00
abstract::Suicide and depression are associated with an increased density of alpha2-adrenoceptors (radioligand receptor binding) in specific regions of the human brain. The function of these inhibitory receptors involves various regulatory proteins (Gi coupling proteins and G protein-coupled receptor kinases, GRKs), which work ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0720282.x
更新日期:1999-01-01 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::Parkinson's disease is a neurodegenerative movement disorder. The histopathology of Parkinson's disease comprises proteinaceous inclusions known as Lewy bodies, which contains aggregated α-synuclein. Cathepsin D (CD) is a lysosomal protease previously demonstrated to cleave α-synuclein and decrease its toxicity in bot...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12497
更新日期:2014-03-01 00:00:00
abstract::Recovery of AChE activity in the motor end plate region and end plate free region of the rat diaphragm was studied after irreversible inhibition by soman. Recovery was slow during the first 2 days and only 4 S and 10 S molecular forms of AChE were present in the end plate region. However, cytochemical evidence indicat...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb04478.x
更新日期:1981-10-01 00:00:00
abstract::Cultures of myelinated SJL/J fetal mouse spinal cord were incubated with serum and lymphoid cells from syngeneic animals with experimental allergic encephalomyelitis (EAE) induced by syngeneic spinal cord homogenate (SSCH) in complete Freund's adjuvant or others injected with complete Freund's adjuvant alone. After 24...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb05462.x
更新日期:1985-02-01 00:00:00
abstract::Gliomas are the most common primary malignant brain tumor in adults, but current treatment for glioblastoma multiforme (GBM) is insufficient. Even though glucose is the primary energetic substrate of glioma cells, they are capable of using fatty acids to generate energy. Fatty acid oxidation (FAO) in mitochondria requ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.15124
更新日期:2020-07-12 00:00:00
abstract::Neuron-secreted factors induce astrocytic expression of the glutamate transporter, GLT-1 (excitatory amino acid transporter 2). In addition to their elaborate anatomic relationships with neurons, astrocytes also have processes that extend to and envelop the vasculature. Although previous studies have demonstrated that...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14135
更新日期:2017-12-01 00:00:00
abstract::Trichloroethylene, a common industrial solvent and a metabolic precursor of chloral hydrate, occurs widely in the environment. Chloral hydrate, which is also used as a hypnotic, has been found to condense spontaneously with tryptamine, in vivo, to give rise to a highly unpolar 1-trichloromethyl-1,2,3,4-tetrahydro-beta...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02710.x
更新日期:2004-10-01 00:00:00
abstract::Mutations within the amyloid-beta (Abeta) domain of the amyloid precursor protein (APP) typically generate hemorrhagic strokes and vascular amyloid angiopathy. In contrast, the Arctic mutation (APP E693G) results in Alzheimer's disease. Little is known about the pathologic mechanisms that result from the Arctic mutati...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.04443.x
更新日期:2007-05-01 00:00:00
abstract::The inhibitors of apoptosis (IAPs) are emerging as key proteins in the control of cell death. In this study, we evaluated the expression and subcellular distribution of the antiapoptotic protein X-linked IAP (XIAP), and its interactions with the XIAP-associated factor 1 (XAF1) in neonatal rat brain following hypoxia-i...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05482.x
更新日期:2008-08-01 00:00:00