[Efficacy and safety of ropinirole in the treatment of Parkinson's disease: a multi-center, randomized, double-blind and bromocriptine-controlled trial].

Objective: To explore the efficacy and safety of ropinirole in the treatment of Parkinson's disease.

Methods: From November 2005 to April 2007, a total of 221 subjects from 7 hospitals of Beijing, Lanzhou and Wuhan participated in a 12-week multi-center, randomized, bromocriptine-controlled, double-blind, double-dummy and parallel-group trial. The efficacy of ropinirole was assessed with the unified Parkinson's disease rating scale (UPDRS) score, "off" time according to the patient's diary and the overall evolution of clinical efficacy.

Disruption of neocortical histone H3 homeostasis by soluble Aβ: implications for Alzheimer's disease.

Amyloid-β peptide (Aβ) fragment misfolding may play a crucial role in the progression of Alzheimer's disease (AD) pathophysiology as well as epigenetic mechanisms at the DNA and histone level. We hypothesized that histone H3 homeostasis is disrupted in association with the appearance of soluble Aβ at an early stage in AD progression. We identified, localized, and compared histone H3 modifications in multiple model systems (neural-like SH-SY5Y, primary neurons, Tg2576 mice, and AD neocortex), and narrowed our focus to investigate 3 key motifs associated with regulating transcriptional activation and inhibition: acetylated lysine 14, phosphorylated serine 10 and dimethylated lysine 9.

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up.

Background: Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly common autoimmune disorder mediated by antibodies to certain subunit of the N-methyl-D-aspartate receptor. Recent literatures have described anti-thyroid and infectious serology in this encephalitis but without follow-up.

Case Presentation: A 17-year-old Chinese female patient presented with psychiatric symptoms, memory deficits, behavioral problems and seizures.

High throughput monitoring of amyloid-β(42) assembly into soluble oligomers achieved by sensitive conformation state-dependent immunoassays.

Accumulation of small soluble assemblies of amyloid-β (Aβ)(42) in the brain is thought to play a key role in the pathogenesis of Alzheimer's disease. As a result, there has been much interest in finding small molecules that inhibit the formation of synaptotoxic Aβ(42) oligomers that necessitates sensitive methods for detecting the initial steps in the oligomerization of Aβ(42). Modeling suggests that oligomerized Aβ(42) adopts a conformation in which the C-terminus is embedded in the center, whereas the N-terminus is exposed at the periphery of the oligomer.

Inhibition of calcineurin-mediated endocytosis and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors prevents amyloid beta oligomer-induced synaptic disruption.

Synaptic degeneration, including impairment of synaptic plasticity and loss of synapses, is an important feature of Alzheimer disease pathogenesis. Increasing evidence suggests that these degenerative synaptic changes are associated with an accumulation of soluble oligomeric assemblies of amyloid beta (Abeta) known as ADDLs. In primary hippocampal cultures ADDLs bind to a subpopulation of neurons.

[Studies on heredity rule of the first genealogy regarding fatal familial insomnia in Henan province].

Objective: To investigate the epidemiological, genealogic characteristic, familial history of the families with fatal familial insomnia, its clinical and pathological features as well as the heredity rule of related genes.

Methods: 135 familial members of 7 eras were studied. Vein blood samples from patients as well as from some familial members were collected.

Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric a{beta}.

Accumulation of amyloid beta (Abeta) oligomers in the brain is toxic to synapses and may play an important role in memory loss in Alzheimer disease. However, how these toxins are built up in the brain is not understood. In this study we investigate whether impairments of insulin and insulin-like growth factor-1 (IGF-1) receptors play a role in aggregation of Abeta.

Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers.

Synapse deterioration underlying severe memory loss in early Alzheimer's disease (AD) is thought to be caused by soluble amyloid beta (Abeta) oligomers. Mechanistically, soluble Abeta oligomers, also referred to as Abeta-derived diffusible ligands (ADDLs), act as highly specific pathogenic ligands, binding to sites localized at particular synapses. This binding triggers oxidative stress, loss of synaptic spines, and ectopic redistribution of receptors critical to plasticity and memory.

A patient with Creutzfeldt-Jakob disease with an insertion of 7 octa-repeats in the PRNP gene: molecular characteristics and clinical features.

Background: We evaluated the features of neuropathology, abnormal prion protein (PrP) molecules, and clinical data of a Chinese woman diagnosed with familiar Creutzfeldt-Jakob disease (CJD), having 7 octa-repeats inserted with codon 129 methionine homozygote in the PRNP gene.

Methods: Neuropathologic characteristics of the brain were analyzed by hemotoxylin-eosin stain and electronic microscopy. The presence of abnormal PrP in brains was detected by proteinase K and PrP molecules were evaluated by deglycosylation assay.

Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer's disease.

Characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system respectively, it is now widely recognized that type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share several common abnormalities including impaired glucose metabolism, increased oxidative stress, insulin resistance and amyloidogenesis. Several recent studies suggest that this is not an epiphenomenon, but rather these two diseases disrupt common molecular pathways and each disease compounds the progression of the other. For instance, in AD the accumulation of the amyloid-beta peptide (Abeta), which characterizes the disease and is thought to participate in the neurodegenerative process, may also induce neuronal insulin resistance.

Amyloid beta oligomers induce impairment of neuronal insulin receptors.

Recent studies have indicated an association between Alzheimer's disease (AD) and central nervous system (CNS) insulin resistance. However, the cellular mechanisms underlying the link between these two pathologies have not been elucidated. Here we show that signal transduction by neuronal insulin receptors (IR) is strikingly sensitive to disruption by soluble Abeta oligomers (also known as ADDLs).

Treatment of scrapie pathogen 263K with tetracycline partially abolishes protease-resistant activity in vitro and reduces infectivity in vivo.

Objective: To study the possible effect of tetracycline on protease-resistant activity in vitro and infectivity in vivo of a scrapie strain 263K.

Methods: Scrapie pathogens were incubated with tetracycline at different concentrations for various periods of time and protease-resistant PrP signals were evaluated with proteinase K-treatment and Western blots. The preparations treated with tetracycline were intracerebrally inoculated into golden hamsters and typical TSE manifestations were noted.

Expression of annexin A2 in GABAergic interneurons in the normal rat brain.

Expression of the Ca(2+)-dependent phospholipids binding protein annexin A2 (ANX2) in the brain is thought to be largely associated with brain pathological conditions such as tumor, inflammation, and neurodegeneration. The recent findings that ANX2 heterotetramer is involved in learning and neuronal activities necessitates a systematic investigation of the physiological expression of ANX2 in the brain. With combination of in situ hybridization and immunohistochemistry, ANX2 mRNA and protein were specifically detected in a group of GABAergic interneurons throughout the brain.

Wernicke's encephalopathy in nonalcoholic patients: clinical and pathologic features of three cases and literature reviewed.

Three cases of Wernicke's encephalopathy in nonalcoholic patients diagnosed by postmortem examination were reported to improve the recognition of this disease. All three cases were male, ages ranged from 33 to 73 years old. All the cases had a clinical history of malnutrition but no history of chronic alcoholism.

Insulin receptor signaling in long-term memory consolidation following spatial learning.

Evidence has shown that the insulin and insulin receptor (IR) play a role in cognitive function. However, the detailed mechanisms underlying insulin's action on learning and memory are not yet understood. Here we investigated changes in long-term memory-associated expression of the IR and downstream molecules in the rat hippocampus.

Increased glucose tolerance and reduced adiposity in the absence of fasting hypoglycemia in mice with liver-specific Gs alpha deficiency.

The G protein G(s)alpha is essential for hormone-stimulated cAMP generation and is an important metabolic regulator. We investigated the role of liver G(s)-signaling pathways by developing mice with liver-specific G(s)alpha deficiency (LGsKO mice). LGsKO mice had increased liver weight and glycogen content and reduced adiposity, whereas survival, body weight, food intake, and metabolic rates at ambient temperature were unaffected.

[Expression of human cytomegalovirus immediate early gene in the intracranial artery walls of atherosclerosis].

Objective: Human cytomegalovirus (HCMV), especially the immediate early (IE) gene of the virus, has been implicated in the pathogenesis of atherosclerosis. The aim of this study was to confirm the presence of HCMV IE gene DNA in intracranial artery walls and the association of the virus with the development of atherosclerosis.

Methods: HCMV IE gene was tested in formaldehyde-fixed intracranial arteries from 35 cases with cerebral atherosclerosis and 20 negative controls.

Specific localization of the annexin II heterotetramer in brain lipid raft fractions and its changes in spatial learning.

Annexin-II (AII) is a Ca(2+)-dependent phospholipid-binding protein that is present in both intracellular and extracellular compartments. In the present study AII immunoreactivity was found in a subpopulation of neurons in specific brain regions, including the cerebral cortex and the surface of hippocampal pyramidal neurons from adult rats. AII from synaptic membranes was detected by immunoblotting as multiple species containing the monomer (AII36) and heterotetramer (AIIt).

Insulin and the insulin receptor in experimental models of learning and memory.

Insulin is best known for its action on peripheral insulin target tissues such as the adipocyte, muscle and liver to regulate glucose homeostasis. In the central nervous system (CNS), insulin and the insulin receptor are found in specific brain regions where they show evidence of participation in a variety of region-specific functions through mechanisms that are different from its direct glucose regulation in the periphery. While the insulin/insulin receptor associated with the hypothalamus plays important roles in regulation of the body energy homeostasis, the hippocampus- and cerebral cortex-distributed insulin/insulin receptor has been shown to be involved in brain cognitive functions.

Impairment of phosphatase 2A contributes to the prolonged MAP kinase phosphorylation in Alzheimer's disease fibroblasts.

The serine/threonine phosphatase 2A (PP2A) has been implicated in the pathogenesis of Alzheimer's disease (AD) due to its important role in regulating dephosphorylation of the microtubule-associated protein tau and mitogen-activated protein (MAP) kinase. In the present study, we show that PP2A was responsible for dephosphorylation of the extracellular signal-regulated kinase 1/2 (Erk1/2) following its activation by BK stimulation. Abnormal gene and protein expressions of PP2A, as well as its activity, were found to contribute to the abnormally prolonged Erk1/2 phosphorylation in the AD fibroblasts.

Gene expression of alpha-endosulfine in the rat brain: correlative changes with aging, learning and stress.

Endosulfine (EDSF) belongs to a highly conserved cAMP-regulated phosphoprotein (ARPP) family and was first isolated from ovine brain as a possible endogenous ligand for sulfonylurea receptors. To explore its involvement in brain functions, we investigated regional distribution of alpha-EDSF gene expression in the rat brain, and its regulation under physiological and pathological conditions. The majority of alpha-EDSF gene was expressed in the pyramidal neurons, which represent the principal excitatory neurons in various brain regions.

c-Src protein tyrosine kinase activity is required for muscarinic receptor-mediated DNA synthesis and neurogenesis via ERK1/2 and c-AMP-responsive element-binding protein signaling in neural precursor cells.

The G protein-coupled muscarinic acetylcholine receptor (mAChR) isoforms have been identified in neural stem/progenitor (or precursor) cells. In previous studies, activation of these receptors induced elevations in intracellular Ca(2+) signals and mitogen-activated protein (MAP) kinase activity that led to enhanced DNA synthesis along with neurogenesis in neural precursor cells. Here we report that the nonreceptor protein tyrosine kinase c-src activity is required for the muscarinic receptor-activated MAP kinase and cAMP-responsive element-binding protein (CREB).

MAP kinase signaling cascade dysfunction specific to Alzheimer's disease in fibroblasts.

Mitogen-activated protein kinases (such as Erk1/2) regulate phosphorylation of the microtubule-associated protein tau and processing of the amyloid protein beta, both events critical to the pathophysiology of Alzheimer's disease (AD). Here we report that enhanced and prolonged Erk1/2 phosphorylation in response to bradykinin (BK) was detected in fibroblasts of both familial and sporadic AD, but not age-matched controls (AC). The AD-associated abnormality in Erk1/2 phosphorylation was not seen in fibroblasts from Huntington's disease patients with dementia.

Secretion of Annexin II via activation of insulin receptor and insulin-like growth factor receptor.

Annexin II is secreted into the extracellular environment, where, via interactions with specific proteases and extracellular matrix proteins, it participates in plasminogen activation, cell adhesion, and tumor metastasis and invasion. However, mechanisms regulating annexin II transport across the cellular membrane are unknown. In this study, we used coimmunoprecipitation to show that Annexin-II was bound to insulin and insulin-like growth factor-1 (IGF-1) receptors in PC12 cells and NIH-3T3 cells overexpressing insulin (NIH-3T3(IR)) or IGF-1 receptor (NIH-3T3(IGF-1R)).