Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease.

Impaired amyloid-β clearance from the brain is a core pathological event in Alzheimer's disease. The therapeutic effect of current pharmacotherapies is unsatisfactory, and some treatments cause severe side effects. The meningeal lymphatic vessels might be a new route for amyloid-β clearance.

Immunization with Bacillus Calmette-Guérin (BCG) alleviates neuroinflammation and cognitive deficits in APP/PS1 mice via the recruitment of inflammation-resolving monocytes to the brain.

The immune system plays a crucial role in the progression of Alzheimer's disease (AD). Recently, immune-dependent cascade induced by systemic immune activation has been verified to play a beneficial role in AD mouse models. Here, we tested whether Bacillus Calmette-Guérin (BCG) immunization alters AD pathology and cognitive dysfunction in APP/PS1 AD mouse model, and with 4Aβ1-15 vaccination as positive control.

Glucocorticoids Prevent Enterovirus 71 Capsid Protein VP1 Induced Calreticulin Surface Exposure by Alleviating Neuronal ER Stress.

Severe hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) always accompanies with inflammation and neuronal damage in the central nervous system (CNS). During neuronal injuries, cell surface-exposed calreticulin (Ecto-CRT) is an important mediator for primary phagocytosis of viable neurons by microglia. Our data confirmed that brainstem neurons underwent neuronophagia by glia in EV71-induced death cases of HFMD.

Postnatal development of nestin positive neurons in rat basal forebrain: different onset and topography with choline acetyltransferase and parvalbumin expression.

Our previous studies identified a sub-population of cholinergic neurons which express nestin in the rostral part of the basal forebrain (BF) in normal adult rats. In the present study, the postnatal developmental patterns of nestin, choline acetyl transferase (ChAT) and parvalbumin (PV) positive neurons were explored by means of immunohistochemistry combined with immunofluorescence double label methods. Compared with early onset of ChAT expression (from P1) and delayed onset of PV expression (from P16), nestin positive activity was detected in the BF from P9 and co-expressed by parts of the ChAT positive neurons within the same region during the whole postnatal development process.

[Molecular mechanisms of Arg77Cys missense mutation and Arg174stop nonsense mutation of factor XIII A gene causing severe factor XIII deficiency].

The present study was aimed to investigate the molecular mechanisms responsible for the pathogenesis of severe factor XIII (FXIII) deficiency. Site-directed mutagenesis was conducted to obtain human FXIIIA expression plasmids bearing the mutations. Wild type FXIIIA recombinant plasmid (pcDNA3.

Superimposing the 27 crystal protein/inhibitor complexes of β-secretase to calculate the binding affinities by the linear interaction energy method.

BACE-1 is an important target for designing therapeutic agents for the treatment of Alzheimer's disease. An improved linear interaction energy (LIE) model has been developed to calculate the binding free energies of β-secretase (BACE-1) by superimposing the 27 crystal BACE-1/inhibitor complexes to put a diverse set of 27 co-crystallized ligands into the binding pocket. These co-crystallized conformations of ligands were set as the initial binding conformations for LIE simulation.

Chemical identification of nestin-immunoreactive neurons in the rat basal forebrain: a re-examination.

This study explores recently identified neurons that express the protein nestin in the medial septum-diagonal band of Broca (MS-DBB) of adult rats and humans. These nestin positive neurons from MS-DBB are known to project to the hippocampus and frontal cortex of the brain. However, their chemical identification has not been fully elucidated.

Differences in c-jun and nNOS expression levels in motoneurons following different kinds of axonal injury in adult rats.

In the peripheral nervous system (PNS), root avulsion causes motoneuron degeneration, but the majority of motoneurons can survive axotomy. In order to study the mechanism of motoneuron degeneration, we compared the expression patterns of c-jun and neuronal nitric oxide synthase (nNOS), the well-known molecular players in PNS regeneration and degeneration, among adult rats having undergone axotomy (Ax), avulsion (Av), or pre-axotomy plus secondary avulsion (Ax + Av) of the brachial plexus. Our results showed that the highest and longest-lasting c-jun activation occurred in Ax, which was much stronger than those in Av and Ax + Av.

Effects of the aqueous extract of the Chinese medicine Danggui-Shaoyao-San on rat pineal melatonin synthesis.

Objectives: The purpose of this study is to investigate if the aqueous extract of the Chinese medicine Danggui-Shaoyao-San (DSS) can increase the plasma level of melatonin and enhance the function of the pineal gland of naturally aged rats.

Methods: The rats were treated with DSS at doses of 3ml or same volume of distilled water by oral administration at 11 p.m.

[Immunologic tolerance of anti-Abeta antibody in the sera of AD patients].

Aim: To characterize anti-amyloid-beta antibodies in the sera of Alzheimer's disease(AD) patients.

Methods: A special tissue amyloid plaque immunoreactivity (TAPIR) examinations of brains of Tg2576 mice was carried out. Abeta(42)-GST fusion protein was detected by Western blot.

[Synthesizing A beta(1-15) multiple antigen peptide vaccine by indirect conjugation and its immunological activity].

Aim: To explore the method of synthesizing the A beta(1-15) multiple antigen peptide (MAP) vaccine and to identify its quality and the immunological activity.

Methods: MAP A beta(1-15) was synthesized by indirect conjugation and analyzed by RP-HPLC,SDA-PAGE and amino acid analysis. Then, C57BL/6 mice were immunized with synthesized MAP A beta(1-15).

Effect of temperature on the activation of myocardial KATP channel in guinea pig ventricular myocytes: a pilot study by whole cell patch clamp recording.

Background: The myocardial ATP sensitive potassium channel (K(ATP) channel) has been known for more than two decades, the properties of this channel have been intensively investigated, especially the myocardial protection effect by opening this channel. Numerous studies, including hypothermic, using K(ATP) agonists to achieve a hyperpolarizing cardioplegic arrest, have shown a better myocardial protection than potassium arrest. However, there is no evidence showing that K(ATP) channel could be opened by its agonists under profound hypothermia.

White matter damage of patients with Alzheimer's disease correlated with the decreased cognitive function.

Increasing evidence demonstrates that there is marked damage and dysfunction in the white matter in Alzheimer's disease (AD). The present study investigates the nature of white matter damage of patients with Alzheimer's disease with diffusion tensor magnetic resonance imaging (DTI) and analyses the relationship between the white matter damage and the cognition function. DTI, as well as T1 fluid attenuated inversion recovery (FLAIR) and T2-FLAIR, was performed on probable patients of Alzheimer's disease, and sex and age matched healthy volunteers to measure the fractional anisotropy (FA) and mean diffusivity (MD) in the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, and the white matter of frontal, temporal, parietal, and occipital lobes.

Specific humoral immune responses in rhesus monkeys vaccinated with the Alzheimer's disease-associated beta-amyloid 1-15 peptide vaccine.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by overproduction of beta-amyloid (Abeta), with the subsequent pathologic deposition of Abeta which is important for memory and cognition. Recent studies showed murine models of AD and AD patients inoculated with Abeta(1-42) peptide vaccine had a halted or delayed pathological progression of AD. Unfortunately, the clinical phase IIa trial of Abeta(1-42) peptide vaccine (AN1792) was halted prematurely because of episodes of menigoencephalitis in 18 of the vaccinated patients.

[Specific humoral immune response in Rhesus monkeys vaccinated immune response with Abeta42 peptide vaccine].

Aim: To observe the humoral immuneresponse in Rhesus monkey induced by Abeta42 peptide vaccination.

Methods: Five male Rhesus monkeys were received intramuscular injection of Abeta42 peptide vaccine at 0, 2nd, 6th, 10th, 14th, 18th, 22th week. The titers and Ig subclasses of the serum anti-Abeta42 antibody were measured by ELISA.

[Fusion expression of human Abeta42 recombinant protein and detection of Abeta antibody].

Objective: To clone and express the recombinant amyloid beta-protein (Abeta(42)) antigen and develop a method for detecting Abeta antibody.

Methods: Two partially complementary fragments of Abeta(42) gene were chemically synthesized for constructing the Abeta(42) gene by PCR. The resultant Abeta(42) gene fragment was subcloned into pGEX-2T expression vector for inducing the expression of GST-Abeta(42) fusion protein, which was purified by affinity chromatography.

Survival, regeneration and functional recovery of motoneurons after delayed reimplantation of avulsed spinal root in adult rat.

We have established that extensive reinnervation and functional recovery follow immediate reimplantation of avulsed ventral roots in adult rats. In the present study, we examined the consequences of reimplantation delayed for 2 weeks after avulsion of the C6 spinal root. Twelve and 20 weeks after delayed reimplantation, 57% and 53% of the motoneurons in the injured spinal segment survived.

[Antibody production and its neutralization of Abeta42's cytoxicity in BALB/c mice induced by Abeta42 and its subunit vaccines].

Aim: To explore the production of anti-Abeta42 antibody after immunization with Abeta42 and its subunit peptide vaccines.

Methods: Seventy five male BALB/c with the age of 6 weeks were randomly divided into 5 groups, namely, control group, Abeta42 group, Abeta(36-42) group, Abeta(1-15)group and F Abeta(1-15) group. The BALB/c mice were immunized four times with PBS+MF59 adjuvant, Abeta42+MF59, Abeta(36-42)+heptalysine (MAP)+MF59, Abeta(1-15)+MAP+MF59 and Abeta(1-15)+MAP+Freud's adjuvant, respectively.

Survival, regeneration and functional recovery of motoneurons in adult rats by reimplantation of ventral root following spinal root avulsion.

We investigated the functional recovery of motoneurons after reimplanting an avulsed ventral root in a rat model of traction injury. The eighth cervical root (C8) was avulsed by controlled traction and immediately reimplanted to the spinal cord. Spinal nerves from neighbouring segments (C5, C6, C7 and T1) were ligated and cut.