Abstract:
:Cathepsin D (CTSD) deficiencies are fatal neurological diseases that in human infants and in sheep are characterized by extreme loss of neurons and myelin. To date, similar morphological evidence for myelin disruption in CTSD knockout mice has not been reported. Here, we show that CTSD deficiency leads to pronounced myelin changes in the murine brain: myelin-related proteolipid protein and myelin basic protein were both markedly reduced at postnatal day 24, and the amount of lipids characteristically high in myelin (e.g. plasmalogen-derived alkenyl chains and glycosphingolipid-derived 20- and 24-carbon acyl chains) were significantly lowered compared with controls. These changes were accompanied by ultrastructural alterations of myelin, including significant thinning of myelin sheaths. Furthermore, in CTSD knockout brains there was a pronounced accumulation of cholesteryl esters and abnormal levels of proteins related to cholesterol transport, with an increased content of apolipoprotein E and a reduced content of ATP-binding cassette transporter A1. These results provide evidence for dysmyelination and altered trafficking of cholesterol in brains of CTSD knockout mice, and warrant further studies on the role of lipid metabolism in the pathogenesis of CTSD deficiencies.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Mutka AL,Haapanen A,Käkelä R,Lindfors M,Wright AK,Inkinen T,Hermansson M,Rokka A,Corthals G,Jauhiainen M,Gillingwater TH,Ikonen E,Tyynelä Jdoi
10.1111/j.1471-4159.2009.06440.xsubject
Has Abstractpub_date
2010-01-01 00:00:00pages
193-203issue
1eissn
0022-3042issn
1471-4159pii
JNC6440journal_volume
112pub_type
杂志文章abstract::Immunoaffinity chromatography with a monoclonal antibody produced against bovine tau protein was used to purify tau proteins from human brain. Fifty grams of brain tissue yielded approximately 2 mg of pure tau proteins. The affinity-purified human tau was used to produce a high-titered rabbit anti-human tau serum. The...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb09754.x
更新日期:1992-02-01 00:00:00
abstract::Previous studies point to quaternary assembly of dopamine transporters (DATs) in oligomers. However, it is not clear whether the protomers function independently in the oligomer. Is each protomer an entirely separate unit that takes up dopamine and is inhibited by drugs known to block DAT function? In this work, human...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13025
更新日期:2015-04-01 00:00:00
abstract::White matter infarct induces demyelination and brain dysfunction. We previously reported that transplantation of brain microvascular endothelial cells improved the behavioral outcome and promoted remyelination by increasing the number of oligodendrocyte precursor cells in the rat model of white matter infarct. In this...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14949
更新日期:2020-06-01 00:00:00
abstract::Extracellular levels of norepinephrine (NE) and glutamate (Glu) in the ventral bed nucleus of the stria terminalis (vBNST) of saline- and chronic morphine-treated rats, with or without withdrawal, were studied by means of the in vivo microdialysis technique in anesthetized rats. In addition, the tissue concentration o...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2000.0750741.x
更新日期:2000-08-01 00:00:00
abstract::Kindling induces long-term adaptations in neuronal function that lead to a decreased threshold for induction of seizures. In the present study, the influence of amygdala kindling on levels of mRNA for the immediate-early genes (IEGs) c-fos, c-jun, and NGF1-A were examined both before and after an acute electroconvulsi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb11007.x
更新日期:1992-11-01 00:00:00
abstract::Existence of microtubule cytoskeleton at the membrane and submembranous regions, referred as 'membrane tubulin' has remained controversial for a long time. Since we reported physical and functional interaction of Transient Receptor Potential Vanilloid Sub Type 1 (TRPV1) with microtubules and linked the importance of T...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2012.07892.x
更新日期:2012-10-01 00:00:00
abstract::Leucine-rich repeat kinase 2 (LRRK2) is a large multidomain scaffolding protein with kinase and GTPase activities involved in synaptic vesicle (SV) dynamics. While its role in Parkinson's disease has been largely investigated, little is known about LRRK2 physiological role and until now few proteins have been describe...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14778
更新日期:2019-08-01 00:00:00
abstract::Melatonin is neuroprotective because of its antioxidative action, but it also can modify neuronal vulnerability by altering gene expression. 5-Lipoxygenase (5-LO) gene expression is suppressed by the binding of melatonin to its high-affinity nuclear receptors. Recently, we reported that in rats the melatonin deficienc...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.69052220.x
更新日期:1997-11-01 00:00:00
abstract::The murine neuroblastoma N1E-115 cell line contains binding sites for the angiotensin II (Ang II) receptor antagonist 125I-[Sarc1,Ile8]-Ang II (125I-SARILE). Binding of 125I-SARILE to N1E-115 membranes was rapid, reversible, and specific for Ang II-related peptides. The rank order potency of 125I-SARILE binding was th...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb09185.x
更新日期:1989-05-01 00:00:00
abstract::In heterologous expression systems, dopamine transporter (DAT) cell-surface localization is reduced after relatively prolonged exposure to d-amphetamine (AMPH) or dopamine (DA), suggesting a role for substrate-mediated regulation of transporter function. Here, we investigated whether brief, repeated periods of substra...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.01133.x
更新日期:2002-10-01 00:00:00
abstract::Perhaps the most reproducible early event induced by the interaction of amyloid beta peptide (A beta) with the cell is the inhibition of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. We recently demonstrated that cytotoxic amyloid peptides such as A beta and human amylin inhibi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1998.71062322.x
更新日期:1998-12-01 00:00:00
abstract::To examine the effects of glutamatergic neurotransmission on amyloid processing, we stably expressed the metabotropic glutamate receptor subtype 1alpha (mGlu-R1alpha) in HEK 293 cells. Both glutamate and the selective metabotropic agonist 1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) rapidly increased phosphatidyli...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.69020704.x
更新日期:1997-08-01 00:00:00
abstract::Animals trained in a passive avoidance task exhibit a transient time-dependent increase in hippocampal neural cell adhesion molecule (NCAM) polysialylation at 12-24 h following the initial learning trial. Using immunocytochemical techniques with a monoclonal antibody that specifically recognises NCAM-polysialic acid h...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.65062796.x
更新日期:1995-12-01 00:00:00
abstract::ATP transport to synaptic vesicles from rat brain has been studied using the fluorescent substrate analogue 1,N6-ethenoadenosine 5'-triphosphate (epsilon-ATP). The increase in intravesicular concentration was time dependent for the first 30 min, epsilon-ATP being the most abundant nucleotide. The complexity of the sat...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0731098.x
更新日期:1999-09-01 00:00:00
abstract::We report on the expression of ionotropic glutamate receptor subunits in primary neuronal cultures from rat cortex, hippocampus and cerebellum and of metabotropic glutamate (mGlu) receptor subtypes in these neuronal cultures as well as in cortical astroglial cultures. We found that the NMDA receptor (NR) subunits NR1,...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00369.x
更新日期:2001-06-01 00:00:00
abstract::The objective of the present study was to explore mechanisms responsible for activation of ion conductances in the initial phases of brain ischemia, particularly for the early release of K+ that precedes massive cell depolarization, and rapid downhill fluxes of K+, Na+, Cl-, and Ca2+. As it has been speculated that a ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb04957.x
更新日期:1990-11-01 00:00:00
abstract::Capsaicin receptors are expressed in primary sensory neurons and excited by heat and protons. We examined the inflammation-induced changes of the level of VR1 capsaicin receptor mRNA in sensory neurons and the sensitivity of primary afferents to capsaicin. Carrageenan treatment induced axonal transport of VR1 mRNA, bu...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00193.x
更新日期:2001-03-01 00:00:00
abstract::Cultures of bovine adrenomedullary chromaffin cells accumulated 1-[methyl-3H]methyl-4-phenylpyridinium ([3H]MPP+) in a time- and concentration-dependent manner with an apparent Km of 0.7 microM and a Vmax of 3 pmol/min/10(6) cells. The uptake was sodium dependent and sensitive to inhibitors of the cell-surface catecho...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb01873.x
更新日期:1989-04-01 00:00:00
abstract::Arg0-Met5-enkephalin (Arg0-MEK) was isolated from bovine striatum and purified to homogeneity. The peptide was extracted with trichloroacetic acid, followed by column chromatography successively on Bio-Sil C8, semipreparative HPLC Radial-Pak C18, fast protein liquid chromatography (FPLC) Mono S, HPLC Ultrasphere-ODS, ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.63051748.x
更新日期:1994-11-01 00:00:00
abstract::The fate of gonadotropin-releasing hormone (GnRH) was examined by a GnRH radioimmunoassay during in vitro incubations of the rat medial basal hypothalamus (MBH). There was a progressive disappearance of exogenous GnRH during MBH incubations. The GnRH degradation could be explained by the release of peptidases from the...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb01640.x
更新日期:1981-02-01 00:00:00
abstract::The effects of treatment of brain membranes with diethyl pyrocarbonate (DEP), a histidine-modifying reagent, on the binding of 3H-labeled Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a]- [1,4]benzodiazepine-3-carboxylate) and [3H]diazepam were compared. DEP pretreatment produced a dose-dependent...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb09406.x
更新日期:1992-08-01 00:00:00
abstract::Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is responsible for the production of PGD(2), the main PG in the CNS. PGD(2) is an endogenous sleep inducer, and it is involved in the control of odor and pain responses and body temperature. In addition, PGD synthase transports lipophilic molecules in the subarachn...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2000.0750460.x
更新日期:2000-08-01 00:00:00
abstract::Stabilized microtubules are required for neuronal morphogenesis and migration. However, the underlying mechanism is not fully understood. In this study, we demonstrate that myosin X (Myo10), which is composed of full-length myosin X (fMyo10) and headless myosin X (hMyo10), is important for axon development. fMyo10 is ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13238
更新日期:2015-10-01 00:00:00
abstract::Activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) are implicated in the pathophysiology of spinal cord injury (SCI). However, the specific functions of individual ERK isoforms in neurodegeneration are largely unknown. We investigated the hypothesis that ERK2 activation may contribute to patholog...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06579.x
更新日期:2010-04-01 00:00:00
abstract::The glial-derived neurotrophic protein S100beta has been implicated in the development and maintenance of the nervous system. S100beta has also been postulated to play a role in mechanisms of neuropathology because of its specific localization and selective overexpression in Alzheimer's disease. However, the exact rel...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.69062294.x
更新日期:1997-12-01 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::Epidermal growth factor (EGF) is a member of a structurally related family containing heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor alpha (TGFalpha) that exerts neurotrophic activity on midbrain dopaminergic neurons. To examine neurotrophic abnormality in Parkinson's disease (PD), we m...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03073.x
更新日期:2005-05-01 00:00:00
abstract::beta-Adrenergic receptor subtypes, beta 1 and beta 2, were studied during pre- and postnatal development in the rat brain. [125I]Iodocyanopindolol (6-300 pmol/L) binding assays in the presence of 5-hydroxytryptamine (0.6-6 mumol/L) were used to measure exclusively beta-adrenergic receptors. In forebrain tissue, satura...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb08235.x
更新日期:1991-09-01 00:00:00
abstract::There is extensive experimental evidence indicating a crucial role for glutamate in epileptogenesis and epileptic activity. The glial glutamate transporters GLT1 and GLAST are proposed to account for the majority of extracellular glutamate re-uptake. In the present study, polyclonal antibodies specific to GLT1 and GLA...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00612.x
更新日期:2001-11-01 00:00:00
abstract::Previous work from our laboratory points to plasma free tryptophan being a useful predictor of brain tryptophan concentration in many circumstances. Other work, in particular various studies on the acute effects of food intake, has emphasized the roles of plasma total tryptophan and of plasma large neutral amino acids...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb08797.x
更新日期:1985-05-01 00:00:00