Abstract:
:Declining levels of estrogen in women result in increases in gonadotropins such as luteinizing hormone (LH) through loss of feedback inhibition. LH, like estrogen, is modulated by hormone replacement therapy. However, the role of post-menopausal gonadotropin increases on cognition has not been evaluated. Here, we demonstrate that the down-regulation of ovariectomy-driven LH elevations using the gonadotropin releasing hormone super-analogue, leuprolide acetate, improves cognitive function in the Morris water maze and Y-maze tests in the absence of E2. Furthermore, our data suggest that these effects are independent of the modulation of estrogen receptors alpha and beta, or activation of CYP19 and StAR, associated with the production of endogenous E2. Importantly, pathways associated with improved cognition such as CaMKII and GluR1-Ser831 are up-regulated by leuprolide treatment but not by chronic long-term E2 replacement suggesting independent cognition-modulating properties. Our findings suggest that down-regulation of gonadotropins is as effective as E2 in modulating cognition but likely acts through different molecular mechanisms. These findings provide a potential novel protective strategy to treat menopause/age-related cognitive decline and/or prevent the development of AD.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Bryan KJ,Mudd JC,Richardson SL,Chang J,Lee HG,Zhu X,Smith MA,Casadesus Gdoi
10.1111/j.1471-4159.2009.06502.xsubject
Has Abstractpub_date
2010-02-01 00:00:00pages
870-81issue
4eissn
0022-3042issn
1471-4159pii
JNC6502journal_volume
112pub_type
杂志文章abstract::The consequences of H(2)O(2)/Fe(2+)-induced oxidative stress on translocation of ethanolamine phosphoglyceride (EPG) and serine phosphoglyceride (SPG) were studied in an oligodendroglia-like cell line (OLN 93) following 3 days of supplementation with 0.1 mM docosahexaenoic acid (DHA) and a series of polar head group p...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00496.x
更新日期:2001-09-01 00:00:00
abstract::We have used biologically active derivatives of beta-nerve growth factor (NGF), modified by biotinylation via carboxyl groups, to target the specific binding of liposomes to cultured rat and human tumor cells bearing NGF receptors. Liposomes, to be used for targeting, were prepared by conjugating streptavidin to phosp...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb05597.x
更新日期:1987-03-01 00:00:00
abstract::The neuronal nitric oxide (NO) synthase generates NO from arginine. NO mediates its physiological effects mainly by stimulating the synthesis of cyclic GMP. We have investigated the role of the arginine availability on the NMDA-induced cyclic GMP accumulation in immature rat brain slices. The effect of NMDA was blocke...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1998.71052139.x
更新日期:1998-11-01 00:00:00
abstract::Hyperglycemia is known to induce microvascular complications, thereby altering blood-brain barrier (BBB) permeability. This study investigated the role of matrix metalloproteinases (MMPs) and their endogenous inhibitors in increased BBB permeability and evaluated the protective effect of S-nitrosoglutathione (GSNO) in...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12939
更新日期:2015-03-01 00:00:00
abstract::JNK/SAPK has been implicated in the pathogenesis of Alzheimer's disease, but the upstream cascade leading to JNK/SAPK activation has not been elucidated in the disease. In this study, we focused on one of the physiological activators of JNK/SAPK, JNK kinase 1 (JKK1). Although there was no significant difference in the...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.01645.x
更新日期:2003-04-01 00:00:00
abstract::Near total inhibition of brain adenosine deaminase (ADA) activity in rats injected with the potent ADA inhibitor 2'-deoxycoformycin (DCF) was previously shown to reduce enzyme activity for up to 50 days during which time the enzyme exhibited reduced sensitivity to in vivo inhibition by DCF. Here, we investigated the b...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb09739.x
更新日期:1992-02-01 00:00:00
abstract::The mechanism(s) underlying neurodegeneration-associated activation of ERK1/2 remain poorly understood. We report that in cultured rat cortical neurons, whose basal ERK1/2 phosphorylation required NMDA receptors (NMDAR), the neurotoxic DNA intercalating drug cisplatin increased ERK1/2 phosphorylation via NMDAR despite...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05550.x
更新日期:2008-09-01 00:00:00
abstract::In invertebrates, the phenolamines, tyramine and octopamine, mediate many functional roles usually associated with the catecholamines, noradrenaline and adrenaline, in vertebrates. The α- and β-adrenergic classes of insect octopamine receptor are better activated by octopamine than tyramine. Similarly, the Tyramine 1 ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12158
更新日期:2013-04-01 00:00:00
abstract::To gain insight into the mechanism through which the neurotransmitter glutamate causally participates in several neurological diseases, in vitro cultured cerebellar granule cells were exposed to glutamate and oxygen radical production was investigated. To this aim, a novel procedure was developed to detect oxygen radi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.68052038.x
更新日期:1997-05-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder characterized pathologically by motor neuron degeneration and associated with aggregation of RNA-binding proteins. TATA-binding protein-associated factor 15 (TAF15) accumulates as cytoplasmic aggregates in neuronal cells, and clearance of these...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.15182
更新日期:2020-09-11 00:00:00
abstract::In the presence of lithium, carbamylcholine chloride (carbachol) and epinephrine increase the accumulation of inositol monophosphate severalfold in hippocampal slices from the rat. The stimulation by carbachol (EC50, 31 microM) is mediated by muscarinic receptors, whereas the effects of epinephrine (EC50, 2 microM) ar...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb02947.x
更新日期:1988-02-01 00:00:00
abstract::Primary cultures of astrocytes from newborn rat brain showed evidence of a substrate-saturable process for glucose transport. The system shows a relatively high affinity for the substrate, with an apparent Km of approximately 1 mM. Maintenance of the cells in medium containing thyroid-hormone-free serum for 3, 6, or 9...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb07239.x
更新日期:1985-11-01 00:00:00
abstract::C-type natriuretic peptide and sodium nitroprusside, a nitric oxide donor molecule, induced large increases in cyclic GMP formation in cultured rat brain capillary endothelial cells. Isoproterenol, a potent agonist of adenylate cyclase, potentiated the actions of C-type natriuretic peptide and of sodium nitroprusside....
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.62062269.x
更新日期:1994-06-01 00:00:00
abstract::Receptors for the nerve growth factor protein (NGF) have been isolated from three cell types [embryonic chicken sensory neurons (dorsal root sensory ganglia; DRG), rat pheochromocytoma (PC12) and human neuroblastoma (LAN-1) cells] and have been shown to be similar with respect to equilibrium dissociation constants. Th...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb10021.x
更新日期:1987-10-01 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::Methyl CpG binding protein 2 (MeCP2) binds to methylated DNA and acts as a transcriptional repressor. Mutations of human MECP2 gene lead to Rett syndrome, a severe neural developmental disorder. Here, we report that the MeCP2 protein can be modified by covalent linkage to small ubiquitin-like modifier (SUMO) and SUMOy...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12523
更新日期:2014-03-01 00:00:00
abstract::Caspase-3 has been identified as a key protease that, by targeting a limited number of proteins, can disrupt essential homeostatic processes and initiate an orderly disassembly of cells, including degradation of genomic DNA. We demonstrate the usefulness of an antibody specific for activated caspase-3 in a model of ne...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2000.0750819.x
更新日期:2000-08-01 00:00:00
abstract::To differentiate the effect of muscle contractile activity from that of motor nerve on oxidative processes in type I muscle, oxidative processes were studied in muscle after immobilization and after denervation. The two processes led to similar atrophy of muscle weight and of the mean diameter of muscle fibers. Disuse...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1980.tb09009.x
更新日期:1980-12-01 00:00:00
abstract::Myelination, during both normal development and with respect to disorders of myelination, is commonly studied by morphological and/or biochemical techniques that assay as their end-points the extent of myelination. The rate of myelination is potentially a more useful parameter, but it is difficult and time-consuming t...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00015.x
更新日期:2001-01-01 00:00:00
abstract::Effects of concanavalin A on transmitter release were investigated in primary cultures of chick sympathetic neurons. The lectin reduced electrically evoked [3H]noradrenaline release by up to 30% with half-maximal inhibition at 0.16 microM. Concanavalin A also reduced the release triggered by extracellular Ca2+ in neur...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1998.71062421.x
更新日期:1998-12-01 00:00:00
abstract::Transporters of the solute carrier 6 (SLC6) family mediate the reuptake of neurotransmitters such as dopamine, norepinephrine, serotonin, GABA, and glycine. SLC6 family members are 12 transmembrane helix-spanning proteins that operate using the transmembrane sodium gradient for transport. These transporters assume var...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.15145
更新日期:2020-08-07 00:00:00
abstract::The release of endogenous 5-hydroxytryptamine (5-HT), substance P (SP), and neurokinin A (NKA) from superfused tissue slices of rat ventral lumbar spinal cord, where SP and NKA coexist with 5-HT in terminals of descending bulbospinal neurons, was investigated. Electrical field stimulation was performed using square-wa...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb02176.x
更新日期:1993-08-01 00:00:00
abstract::Beta-carbolines have been suggested to be involved in the pathogenesis of Parkinson's disease as a result of their structural similarity to the neurotoxin N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The chloral-derived beta-carboline derivative 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) caus...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.00875.x
更新日期:2002-05-01 00:00:00
abstract::Exposure to excessive levels of light induces photoreceptor apoptosis and can be a causative factor in age-related macular degeneration (AMD). However, the cellular events that mediate this apoptotic response are poorly understood. Here, we investigated the roles of endoplasmic reticulum (ER) stress in light-induced c...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12116
更新日期:2013-04-01 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::S-100 proteins are a group of three 21-kilodalton, acidic, Ca2+-binding proteins of the "E-F hand" type shown to regulate several cell activities, including microtubule (MT) assembly-disassembly. We show here that S-100 proteins interact with MTs assembled from either whole microtubule protein or purified tubulin, bot...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb01841.x
更新日期:1989-04-01 00:00:00
abstract::Interleukin-1 (IL-1) is a proinflammatory cytokine released by many cell types that acts in both an autocrine and/or paracrine fashion. While IL-1 is best described as an important mediator of the peripheral immune response during infection and inflammation, increasing evidence implicates IL-1 signaling in the pathoge...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2008.05315.x
更新日期:2008-07-01 00:00:00
abstract::To better understand amyloid-beta (Abeta) metabolism in vivo, we assessed the concentration of Abeta in the CSF and plasma of APP(V717F) (PDAPP) transgenic mice, a model that develops age-dependent Alzheimer's disease (AD)-like pathology. In 3-month-old mice, prior to the development of Abeta deposition in the brain, ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.00889.x
更新日期:2002-04-01 00:00:00
abstract::Myelin basic protein (MBP) dissociated from brain myelin membranes when they were incubated (37 degrees C; pH 7.4) at physiological ionic strength. Zinc ions inhibited, and calcium promoted, this process. Protease activity in the membrane preparations cleaved the dissociated MBP into both small (less than 4 kilodalton...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb01803.x
更新日期:1988-09-01 00:00:00
abstract::Spinocerebellar ataxia type 3 (SCA3) is one of at least nine inherited neurodegenerative diseases caused by an expansion of a polyglutamine tract within corresponding disease-specific proteins. In case of SCA3, mutation of Ataxin-3 results in aggregation of misfolded protein, formation of intranuclear as well as cytos...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12684
更新日期:2014-06-01 00:00:00