Abstract：
:Inhibition of Aβ production and clearance of senile plaques have been considered as potential strategies in the treatment of Alzheimer's disease (AD). Activated protein C (APC) is an important factor in the anticoagulant system. However, whether APC can influence the condition of a chronic neurodegenerative process, such as that present in AD, is unknown. In this study, we found that administration of APC on AD Tg2576 mice significantly reduced amyloid β production and helped to facilitate cognitive improvement. APC could also reduce levels of Aβ40 and Aβ42 produced in APPswe cells, an AD cell model. Further results demonstrated that APC did not change the levels of Aβ-degrading enzymes, insulin-degrading enzyme (IDE), or neprilysin (NEP). Next, we found that APC promoted sAPPα and CTFα release and inhibited sAPPβ and CTFβ release, thereby indicating that APC could regulate Aβ secretion by shifting APP processing from the amyloidogenic pathway toward the nonamyloidogenic pathway. Correspondingly, further study revealed that ADAM-10 expression was increased by APC, suggesting that APC inhibits Aβ secretion through stimulating activity of α-secretase. These findings support the idea that APC could hold therapeutic potential in the treatment of AD.
journal_name
Brain Resjournal_title
Brain researchauthors
Li B,Yu D,Xu Zdoi
10.1016/j.brainres.2013.12.005subject
Has Abstractpub_date
2014-01-30 00:00:00pages
35-44eissn
0006-8993issn
1872-6240pii
S0006-8993(13)01532-1journal_volume
1545pub_type
杂志文章相关文献
BRAIN RESEARCH文献大全abstract：:Changes in GABA(A) receptor alpha(1) subunit gene expression occur in the globus pallidus and substantia nigra pars reticulata following lesions of the nigrostriatal tract. To determine whether these changes are translated at the protein level, we performed quantitative autoradiography with the alpha(1) selective liga...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/s0006-8993(00)02081-3
更新日期：2000-04-17 00:00:00
abstract：:A pathway from the pretectal region to the dorsal division of the lateral geniculate body has been studied by autoradiography in adult cats following injection of tritium-labeled amino acids into the meso-diencephalic border zone. The findings suggest that the pretecto-geniculate connection arises in the ipsilateral n...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(80)90861-6
更新日期：1980-08-11 00:00:00
abstract：:During retinal development, common precursors give rise to various types of cells in a time course specific to each cell type. Previously, we demonstrated that the bHLH gene Hes1 inhibits neuronal differentiation whereas, in Hes1-null retina, precursors prematurely differentiate into neurons and form abnormal rosette-...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2004.01.045
更新日期：2004-04-09 00:00:00
abstract：:Facilitation of cerebellorubral transmission was illustrated in nembutalized cats on paired stimulation of the cerebellar nucleus interpositus by an example of monosynaptic EPSPs of the rubrospinal neurons. It was found that the facilitation stated is not determined by the change in the presynaptic volley of impulses....
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(87)90334-9
更新日期：1987-05-05 00:00:00
abstract：:Motor-related regions of parietal and prefrontal cortices have been shown to selectively activate when observers passively view objects that afford manual grasping. Yet, it remains unknown whether these cortical responses depend on prior motor-related experience with the object being observed. To address this question...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2006.04.059
更新日期：2006-06-30 00:00:00
abstract：:Previous electrophysiological as well as imaging research has contributed to the understanding of impairments in attention, executive functions, and memory in patients with attention-deficit/hyperactivity disorder (ADHD). However, there is a lack of studies investigating ADHD related differences in the gamma range of ...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2008.06.023
更新日期：2008-10-15 00:00:00
abstract：:The effect of isradipine, a dihydropyridine calcium antagonist, on morphine-induced place preference and analgesia in rats and mice was studied. Isradipine (0.6-5.0 mg/kg s.c.) inhibited an acquisition of morphine-induced place preference in rats and mice in a dose-related manner. Isradipine did not affect or strength...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(92)91311-2
更新日期：1992-10-16 00:00:00
abstract：:Intracellular recordings from CA3b/c neurons in rat hippocampal slices showed that reduction of the extracellular Cl- concentration from 136 to 53 mM produced a positive (+10 mV) shift in the reversal potential of GABAergic inhibitory postsynaptic potentials (IPSPs). This shift was not significantly different from the...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(88)91068-2
更新日期：1988-03-29 00:00:00
abstract：:The study examined whether intravenous (i.v.) leptin increased Fos-production in spinally projecting neurons in the hypothalamic paraventricular nucleus (PVN). We combined (i) rhodamine tagged microspheres injected into the upper thoracic spinal cord and (ii) Fos (marker of neuronal activation) immunohistochemistry. E...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/s0006-8993(99)01902-2
更新日期：1999-10-09 00:00:00
abstract：:Previous studies showed the role of basolateral amygdala (BLA) in cannabinoid-induced antinociception. Furthermore, the nucleus accumbens (NAc) plays an important role in mediating the suppression of pain in animal models. The present study extended the role of dopamine receptors within the NAc in antinociceptive effe...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2012.06.023
更新日期：2012-08-30 00:00:00
abstract：:Avian circadian rhythms are regulated by a multiple oscillatory system consisting of the pineal, the suprachiasmatic nucleus (SCN) and the eye. In the present study, ontogeny of circadian clock in the pineal and the SCN of chick embryo was examined using Per2 expression as a marker. A daily rhythmicity of Per2 express...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/s0006-8993(03)03531-5
更新日期：2003-11-14 00:00:00
abstract：:An in vitro autoradiographic technique has been used to localize [125I]omega-conotoxin GVIA binding sites in the brains of normal and cerebellar mutant mice. In the brains of normal mice, the highest densities of binding sites were observed at glomeruli of the olfactory bulb, cerebral cortex, caudate nucleus-putamen, ...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(89)90004-8
更新日期：1989-06-05 00:00:00
abstract：:Loss of dopaminergic neurons from the pars compacta of the substantia nigra is the pathological hallmark of Parkinson's disease (PD) and results in a partial deafferentation to the striatum. Since deafferentation is known to induce transynaptic atrophy of postsynaptic cells, we examined by Golgi impregnation the morph...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(88)90124-2
更新日期：1988-07-05 00:00:00
abstract：:The effects of two specific tyrosine kinase inhibitors on long-term potentiation (LTP) in the dentate gyrus were investigated using anesthetized rats. I.c.v. injection of herbimycin A (1.74 nmol) or lavendustin A (1.31 nmol) before application of tetanic stimulation significantly inhibited the formation of LTP. Howeve...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(93)90315-e
更新日期：1993-09-03 00:00:00
abstract：:Chronic neuropathic pain has demonstrated that coexisting psychiatric disorders are associated with disability and poorer treatment outcomes. Hyperpolarization-activated cyclic nucleotide-gated (HCN, Ih) channels play a major role in pain via hyperexcitability and facilitation of ectopic firing in neurons. Neuronal hy...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2019.03.036
更新日期：2019-08-15 00:00:00
abstract：:Sardinian alcohol non-preferring (sNP) rats, selected for their low ethanol preference and consumption, carry a point mutation (R100Q) in the gene coding for GABA(A) receptor alpha(6) subunit, which becomes more sensitive to diazepam-evoked GABA currents. We performed binding studies in the cerebellum of normal (RR) a...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/s0006-8993(02)04230-0
更新日期：2003-03-28 00:00:00
abstract：:Cell bodies and dendrites of neurones in the thalamic reticular nucleus projecting to the dorsal lateral geniculate nucleus in adult albino rats, were labelled by retrograde transport of horseradish peroxidase (HRP). In the same animals the terminals of cortico-reticular axons were made identifiable by ipsilateral vis...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(81)90685-5
更新日期：1981-02-23 00:00:00
abstract：:Growth hormone releasing factor (GRF) applied by iontophoresis, pressure, and in the perfusate, increased (14.81%) or decreased (45.92%) the firing of paraventricular neurons extracellularly recorded from guinea-pig hypothalamic slices. Effects were similar whatever the mode of application and were elicited in the nan...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(86)90374-4
更新日期：1986-04-23 00:00:00
abstract：:Kindling of the ventral tegmental area (VTA), a major source of the mesolimbic dopamine pathway, was examined in rats. We applied two quantitative measurements of dopamine sensitivity before and 2 weeks after VTA kindling (20 times electrical stimulations (100 microA at 1 min intervals) delivered once per day for 14 c...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2004.01.006
更新日期：2004-04-02 00:00:00
abstract：:The expression of two embryonic intermediate filaments, nestin and vimentin, in the rat brain at days 0 (control), 1, 4, 7 and 14 post-cryoinjury was studied to elucidate their roles in brain injury. Western blot analysis showed that both nestin and vimentin expressions in the ipsilateral cerebral cortex were signific...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2004.09.022
更新日期：2004-12-03 00:00:00
abstract：:Results of the preceding paper32 suggest that bulbo-pontine respiration related units (RRU) could be classed into 4 populations according to the relation of their peak firing frequency to the respiratory cycle: one inspiratory (I) and 3 expiratory (E) (early, mid and late). A further study of their spatial distributio...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(76)90668-5
更新日期：1976-09-17 00:00:00
abstract：:By using the modified detection method, favored patterns can be detected in a total of 44 spontaneous spike trains. Among these the 'periodical burst' discharge of one sympathetic preganglionic neuron and the 'fast-slow' alternative discharge of some hypothalamic neurons have visible characteristics, hence we use them...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(91)90008-j
更新日期：1991-09-20 00:00:00
abstract：:We used amygdala-kindled seizures in rats to study the function of striatal gamma-aminobutyrate (GABA) in the regulation of the seizure threshold of the limbic forebrain. Microinjections of the GABAA antagonist, bicuculline methiodide, 1 pmol, into the caudate-putamen protected rats against amygdala-kindled seizures. ...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(87)91089-4
更新日期：1987-05-19 00:00:00
abstract：:The effect of high concentrations of L-ascorbic acid on the in vivo and in vitro growth of human neuroblastoma has been investigated. Directly implemented into cell culture it decreased the DNA, RNA and protein synthesis, and mitosis of neuroblastoma cells, without affecting normal neuronal cells. In vivo treatment of...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(85)91139-4
更新日期：1985-09-09 00:00:00
abstract：:Tyrosine hydroxylase immunohistochemical analysis was performed on tissue sections through the pallidal complex from Nemistrina monkeys which had been made hemi-parkinsonian by intracarotid MPTP infusion 8-12 months earlier. The side contralateral to the MPTP infusion showed a dense dopaminergic innervation of the pal...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(91)90318-p
更新日期：1991-08-16 00:00:00
abstract：:The ability of membrane-associated peptidases from the brains of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats to metabolize iodinated angiotensin (125I-Ang II) and 125I-Ang III was compared. 125I-Ang II was metabolized to 125I-Ang III and other fragments exclusively by membrane-assoc...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(90)90844-2
更新日期：1990-10-08 00:00:00
abstract：:Many lines of evidence support the importance of the nucleus accumbens (NAC) for ethanol-reinforced behavior. The nature of the neuronal activity that occurs in this region during ethanol self-administration is not known. We recorded from ensembles of single-units primarily located within the shell of the NAC during o...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/s0006-8993(98)01245-1
更新日期：1999-01-30 00:00:00
abstract：:To gain insight into ATP-binding cassette transporter A1 (ABCA1) function and its potential role in AD pathology, we analyzed the expression of the cholesterol transporter ABCA1 in postmortem hippocampus from persons at different stages of dementia and AD associated neuropathology relative to cognitively intact normal...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2010.01.006
更新日期：2010-03-08 00:00:00
abstract：:In animals with retinal degeneration, the presence of activated microglial cells in the outer retina during the early stages of injury suggests that they may be involved in the ensuing photoreceptor cell death. In the following study, we investigated the effects of rat retina-derived microglial cells on a photorecepto...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/s0006-8993(99)01625-x
更新日期：1999-07-31 00:00:00
abstract：:Tyrosine hydroxylase immunohistochemical examination of the mesencephalon of severely parkinsonian MPTP-treated macaque fascicularis monkeys revealed a marked loss of substantia nigra pars compacta (SNc) neurons in both medial and central portions of the nucleus with a relative sparing of neurons in the dorsal-most po...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(87)90691-3
更新日期：1987-05-12 00:00:00
