Abstract:
:Niemann-Pick disease type C (NPC) is a neurovisceral disorder characterized by lysosomal sequestration of endocytosed LDL-cholesterol, premature and abnormal enrichment of cholesterol in trans Golgi cisternae and accompanying anomalies in intracellular sterol trafficking. In addition to cholesterol, the NPC lesion has also been shown to impact the metabolism of sphingolipids. Lipids, more particularly glycolipids, were studied in brain tissue from eight cases with proven NPC, ranging from 21 fetal weeks to 19 years of age (one case with rapidly fatal neonatal cholestatic icterus, three cases with infantile neurological onset, one late infantile and two juvenile neurological cases). In gray matter, the concentrations of total cholesterol, sphingomyelin and total gangliosides were within the normal range in all cases. In white matter, a severe loss of galactosylceramide and other myelin lipids (including cholesterol) was prominent in patients with the neurological severe infantile form (levels similar to those in 6-8 month-old infants) or the late infantile form of the disease, but only a slight decrease was observed in patients with a juvenile neurological onset. Analysis of the ganglioside profiles and study of minor neutral glycolipids revealed striking abnormalities, although not present at the fetal stage. In cerebral cortex, gangliosides GM3 and GM2 showed a significant increase, 10-15 fold and 3-5-fold the normal level, respectively, with already some abnormalities in a 3-month-old patient. Except in the latter patient, a prominent storage of glucosylceramide, lactosylceramide and gangliotriaosylceramide (asialo-GM2) was observed, with 10-50-fold increases from the normal concentration. The fatty acid composition of these glycolipids suggests that they have a neuronal origin. A slight increase of globotriaosyl- and globotetraosylceramide and of more complex neutral glycolipids also occurred. While ganglioside changes were essentially similar in gray and white matter, changes of the neutral glycolipids were only minimal in the latter. Our data are in good accordance with previous studies and provide additional information. They emphasize that, apart a varying demyelinating process (most pronounced in children with a severe infantile neurological form) brain lipids abnormalities are essentially located to the gray matter. They confirm and give more precise information on the glycolipid nature of the neuronal storage, and establish that a similar type of changes occurs in the different neurological forms of the disease. Yet, our study indicates that glycolipid changes in brain do not occur before a few months after birth, possibly at a period concomitant with the onset of neurological symptoms, in contrast to the very early glycolipid abnormalities observed in non-neural organs. Glycolipid changes rather similar to those seen in NPC brain, in particular for gangliosides, have been described for other lysosomal disorders such as Niemann-Pick type A and mucopolysaccharidoses. The glucosyl-and lactosylceramide accumulation, however, is more striking in NPC, especially taking into account that there is no other known storage in NPC brain. Some neuropathological changes, such as ectopic neurites, could be related to the glycolipid changes. Metabolic studies in cultured fibroblasts combined to the observation that no lipids other than glycolipids accumulate in brain suggest that the NPC gene products possibly participate in intracellular transport or regulate metabolism of glycolipids.
journal_name
Neurochem Resjournal_title
Neurochemical researchauthors
Vanier MTdoi
10.1023/a:1022575511354keywords:
subject
Has Abstractpub_date
1999-04-01 00:00:00pages
481-9issue
4eissn
0364-3190issn
1573-6903journal_volume
24pub_type
杂志文章,评审abstract::We review here the possible mechanisms of neuronal degeneration caused by L-cysteine, an odd excitotoxin. L-Cysteine lacks the omega carboxyl group required for excitotoxic actions via excitatory amino acid receptors, yet it evokes N-methyl-D-aspartate (NMDA) -like excitotoxic neuronal death and potentiates the Ca2+ i...
journal_title:Neurochemical research
pub_type: 杂志文章,评审
doi:10.1023/a:1007616817499
更新日期:2000-10-01 00:00:00
abstract::Rett syndrome (RS) is an X-linked neurodevelopmental disorder mostly involving mutations in the gene for methyl-CpG-binding protein 2 (MECP2). Ganglioside abnormalities were previously found in cerebrum and cerebellum in RS patients. We evaluated total lipid distribution in cerebrum/brainstem, hippocampus, and cerebel...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-008-9874-7
更新日期:2009-06-01 00:00:00
abstract::Activities toward arachidonyl-labelled phospholipase A2 substrates were assayed in fractions of white matter and cerebral cortex from control subjects and in fractions of demyelinated plaque, normal-appearing white matter and cerebral cortex from subjects who died with multiple sclerosis. Membranous activity at pH 8.6...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00992509
更新日期:1995-11-01 00:00:00
abstract::We studied the effects of transcranial magnetic stimulation (TMS, 60 Hz and 0.7 mT for 4 h/day for 14 days) on oxidative and cell damage caused by olfactory bulbectomy (OBX) in Wistar rats. The levels of lipid peroxidation products and caspase-3 were enhanced by OBX, whereas it prompted a reduction in reduced glutathi...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-010-0172-9
更新日期:2010-08-01 00:00:00
abstract::Neuronal MHC class I proteins have been previously reported to regulate synaptic plasticity. Several reports indicate MHC class I proteins are expressed early during development of the nervous system, suggesting they may also play a role in neuronal development. Using cultured cortical neurons, we show MHC class I pro...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-018-2676-7
更新日期:2019-02-01 00:00:00
abstract::Experimental allergic encephalomyelitis (EAE) is an experimentally induced autoallergic demyelinating disease which is caused by immunization with a particular neuroantigen, such as myelin basic protein (MBP). Results have suggested that protease inhibitors might be useful therapeutically. Leupeptin (acetyl-L-leucyl-L...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00964667
更新日期:1984-10-01 00:00:00
abstract::Neurons, purified by bulk-isolation procedures from 10 day-old rat brain, are 80-90% homogeneous. Contaminants are primarily blood vessels and occasional oligodendroglia. All sizes and shapes of neurons are obtained, as they are isolated from all areas of the brain, except the cerebellum. Neurotransmitter enzyme activ...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00971368
更新日期:1987-01-01 00:00:00
abstract::Protocatechuic acid (PA), a major metabolite of anthocyanins, has been reported to possess antioxidant and anti-inflammatory activities. However, the effects of PA on LPS-induced inflammatory responses in microglia have not been reported. The aim of this study was to investigate the anti-inflammatory effects and molec...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-015-1646-6
更新日期:2015-08-01 00:00:00
abstract::Memory impairment is a major problem afflicting mankind. The association between memory functions and neurotransmitter functions is of great interest for understanding brain function. Serotonergic pathways play an important role in the modulation of memory functions but the importance of its receptor types and subtype...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-012-0839-5
更新日期:2012-10-01 00:00:00
abstract::Excitatory and inhibitory neurotransmission in the central nervous system can be modulated by neurosteroids. We previously found that in rat hippocampal slices allopregnanolone (3α-hydroxy-5α-pregnan-20-one), a positive GABA(A) receptor modulator, suppresses the epileptic discharges induced by 4-aminopyridine (4-AP), ...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-011-0649-1
更新日期:2012-03-01 00:00:00
abstract::During evolution, living organisms develop a specialized apparatus called nociceptors to sense their environment and avoid hazardous situations. Intense stimulation of high threshold C- and Adelta-fibers of nociceptive primary sensory neurons will elicit pain, which is acute and protective under normal conditions. A f...
journal_title:Neurochemical research
pub_type: 杂志文章,评审
doi:10.1007/s11064-008-9711-z
更新日期:2008-10-01 00:00:00
abstract::Intracerebral hemorrhage (ICH) is an important public health problem in neurology, which is not only associated with high mortality but also leading to disability. Yet no satisfactory treatment has been developed. The secondary injury that resulted from a number of self-destructive processes such as neuroinflammation,...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-017-2179-y
更新日期:2017-05-01 00:00:00
abstract::Tanshinone I (TsI) is an important lipophilic diterpene extracted from Danshen (Radix Salvia miltiorrhizae) and has been used in Asia for the treatment of cerebrovascular diseases such as ischemic stroke. In this study, we examined the neuroprotective effect of TsI against ischemic damage and its neuroprotective mecha...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-014-1312-4
更新日期:2014-07-01 00:00:00
abstract::The preventive effect of dietary taurine supplementation on glial alterations in retina of streptozotocin-induced diabetic rats was examined in this study. Blood glucose content, content of taurine, glutamate and
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-008-9763-0
更新日期:2009-02-01 00:00:00
abstract::The control and maintenance of the intracellular redox state is an essential task for cells and organisms. NAD(+) and NADH constitute a redox pair crucially involved in cellular metabolism as a cofactor for many dehydrogenases. In addition, NAD(+) is used as a substrate independent of its redox-carrier function by enz...
journal_title:Neurochemical research
pub_type: 杂志文章,评审
doi:10.1007/s11064-012-0760-y
更新日期:2012-11-01 00:00:00
abstract::The effects of 100microg melatonin injection at postnatal day 5 (PD 5) on the development of the central serotonergic systems in male and female rats were investigated. The contents of serotonin (5-HT) and 5-hydroxy-3-indolacetic acid (5-HIAA) were measured in several extrahypothalamic regions at 3, 10 and 42 weeks of...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1023/a:1007517524179
更新日期:2000-06-01 00:00:00
abstract::The influence of hypothyroidism (HO) induced by treatment with propylthiouracil on lipid composition, receptor responsiveness of M1-muscarinic receptors (M1AChRs) and metabotropic glutamate receptors (mGluRs) as well as on protein kinase C (PKC) activity was investigated in the cerebral cortex of Lewis rats. HO did no...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF02527750
更新日期:1996-05-01 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::Neuronal differentiation and aging are known to involve many genes, which may also be differentially expressed during these developmental processes. From primary cultured cerebral cortical neurons, we have previously identified various differentially expressed gene transcripts from cultured cortical neurons using the ...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-005-8800-5
更新日期:2005-10-01 00:00:00
abstract::Transferrin (Tf), the iron-transport protein of vertebrate serum, is mainly synthesized in hepatocytes but is also found in other cell-types including oligodendrocytes. Our laboratory has characterized in a human oligodendrial cell line the presence of a new Tf transcript containing an alternative exon 1b replacing th...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1023/a:1021692220482
更新日期:2002-11-01 00:00:00
abstract::The effect of ageing and the relationships between the catalytic properties of enzymes linked to Krebs' cycle, electron transfer chain, glutamate and aminoacid metabolism of cerebral cortex, a functional area very sensitive to both age and ischemia, were studied on mitochondria of adult and aged rats, after complete i...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-009-0004-y
更新日期:2009-12-01 00:00:00
abstract::Effects of methylmercury (MetHg) on the specific [3H]flunitrazepam binding were studied in rat cortical and cerebellar P2-fractions in vitro. MetHg did not affect significantly the specific [3H]flunitrazepam binding in unwashed P2-fraction but increased it marginally (by 16%) at 100 microM in washed P2-fraction, in bo...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF01705532
更新日期:1995-06-01 00:00:00
abstract::The long-acting opiate antagonist naltrexone hydrochloride was administered by intraperitoneal injection, in a dose response protocol, to adult rats. The drug was used to observe effects of opiate receptor blockade on cells of the pituitary gland and adjacent hypothalamus. At higher drug doses (5 mg/kg or 10 mg/kg), n...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00964168
更新日期:1984-02-01 00:00:00
abstract::Prevention and amelioration of Mibyou (sub-healthy condition) is the critical target for disease prevention including age-related diseases and cancer although the Mibyou condition is not yet pathologically defined. Since the oxidative stress is an underlying basic etiology associated with many diseases and aging, the ...
journal_title:Neurochemical research
pub_type: 杂志文章,评审
doi:10.1007/s11064-008-9872-9
更新日期:2009-04-01 00:00:00
abstract::The participation of voltage-sensitive Na+ channels (VSSC) on the changes on internal (i) Na+, K+, Ca2+, and on DA, Glu, and GABA release caused by different concentrations of 4-AP was investigated in striatum synaptosomes. TTX, which abolished the increase in Na(i) (as determined with SBFI), induced by 0.1 mM 4-AP on...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1023/b:nere.0000013737.17288.ce
更新日期:2004-02-01 00:00:00
abstract::Incomplete ischemia of the spinal cord was produced in dogs by 40 min occlusion of the abdominal aorta that was followed by 5-40 min of recirculation. Amino acid incorporation into ribosomes in vitro in the presence of venous blood sera was estimated. The most significant reduction in incorporation was produced by ser...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00965210
更新日期:1986-06-01 00:00:00
abstract::In the present study mitochondrial respiratory function of fibroblasts from a patient affected by early-onset parkinsonism carrying the homozygous W437X nonsense mutation in the PINK1 gene has been thoroughly characterized. When compared with normal fibroblasts, the patient's fibroblast mitochondria exhibited a lower ...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-008-9729-2
更新日期:2008-12-01 00:00:00
abstract::The subcellular distribution of Ca2+/calmodulin-stimulated adenylate cyclase activity was studied in comparison with that of guanine nucleotide-stimulated cyclase activity. The distributions of these activities were similar among the crude fractions but differed among the purified subsynaptosomal fractions. The specif...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00965018
更新日期:1986-03-01 00:00:00
abstract::Catecholamine secretion in the bovine adrenal medulla is evoked largely by nicotinic receptor activation. However, bovine adrenal medulla also contain muscarinic receptors that mediate several cell responses. To understand the physiological role of muscarinic receptors in the bovine adrenal medulla it is important to ...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00968406
更新日期:1992-12-01 00:00:00
abstract::The action of electroacupuncture (EA) may be similar to analgesia by electrode stimulation or transcutaneous nerve stimulation. Since EA may directly stimulate nerve activity or indirectly enhance the release of opiate peptides and other neurotransmitter substances, we have used (Na+ + K+)-ATPase as a model to study t...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00964513
更新日期:1984-05-01 00:00:00