Calorie restriction promotes remyelination in a Cuprizone-Induced demyelination mouse model of multiple sclerosis

Metabolic Brain Disease - Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary...     

Dual effects of 3, 4-methylenedioxymethamphetamine （ecstasy） on survival and apoptosis of primary hippocampal neurons

BACKGROUND： 3, 4-methylenedioxymethamphetamine （MDMA, also known as ＂ecstasy＂） has been shown to exhibit neurotoxic effects on the hippocampus. However, exposure to sub-lethal insults of MDMA has been reported to result in neuroprotection. OBJECTIVE： To investigate the effects of MDMA on hippocampal neuronal viability, caspase-3 activity, and mRNA expression of the N-methyI-D-aspartate （NMDA） receptor 2B （NR2B） subunit. DESIGN, TIME AND SETTING： A cytological, in vitro experiment was performed at the Department of Anatomy, School of Medicine, and Department of Toxicology-Pharmacology, Faculty of Pharmacy Tehran University of Medical Sciences in 2008. MATERIALS： MDMA was extracted from ecstasy tablets, which were kindly supplied by the Pharmacology-Toxicology Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran. METHODS： Hippocampal neurons were isolated from Wistar rats at gestational day 18. Following primary culture, hippocampal neuronal viability was detected by MTT assay. Varying concentrations of MDMA （100-5 000 μmol/L） were used to determine lethal concentration 50 （LC50）, which was around 1 500 μmol/L. Five concentrations of MDMA below 1 500 μmol/L （100, 200, 400, 800, and 1 050 μmol/L） were used for the remaining experiments. After 24 hours of MDMA treatment, NR2B mRNA expression was detected by RT-PCR, and caspase-3 relative activity was determined by colorimetric assay. MAIN OUTCOME MEASURES： Hippocampal neuronal viability, caspase-3 activity, and NR2B mRNA expression. RESULTS： MDMA-induced neurotoxicity in hippocampal neuronal cultures was dose-dependent. In high concentrations （1 000-5 000μmol/L） of MDMA, neuronal viability was decreased. However, with a 500 μmol/L dose of MDMA, neuronal viability was significantly increased （P 〈 0.01）. Low concentrations of MDMA （200 and 400μmol/L） significantly decreased caspase-3 activity （P 〈 0.01）, whereas high concentrations of MDMA significantly increased caspase-3 activity （P 〈 0.01）. NR2B subunit mRNA expression was not significantly altered after 100 -1 050 μmol/L MDMA exposure. CONCLUSION： MDMA exhibits dual effects on hippocampal neuronal viability and caspase-3 activity. These effects are independent from NR2B subunit expression levels.     

The effects of simvastatin on ischemia-reperfusion injury of sciatic nerve in adult rats

Severe ischemia to nerve results in fiber degeneration and reperfusion results in oxidative injury to endothelial cells and augments fiber degeneration. Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, the most widely used lipid-lowering drugs, have been demonstrated to play a neuroprotective role. So we evaluated the effectiveness of simvastatin in protecting sciatic nerve from ischemia-reperfusion injury using the model of experimental nerve ischemia. Sixty adult male Sprague-Dawley rats weighing 250-300 g were used. They were divided into ten groups (N=6 per group). We used ischemia model in these groups by occluding the femoral artery and vein with a silk suture 6-0 using slipknot technique. All ischemia groups were rendered in ischemic for 3 h reperfused for various times of zero (0 h), 3 h (3 hour reperfusion), 7 days (7 day reperfusion), 14 days (14 day reperfusion). Half of the groups had experimental simvastatin (1 mg/kg) i.v. injection treatment via tail vein 1 h before ischemia. The other half experienced only ischemia-reperfusion as control groups. After euthanasia, histological samples were taken from distal part of the sciatic nerve. Sections were cut at 5 microm and then were stained with H and E and modified trichrome. We used H and E stain for edema and trichrome gomori for ischemic fiber degeneration. Samples were observed to assess their fiber degeneration and edema changes. By observation the level of fiber degeneration and endoneurial edema were also decreased in these recent groups (in both ischemia and reperfusion duration). In conclusion, pre-ischemic administration of simvastatin exhibits neuroprotective properties in ischemia-reperfusion nerve injury.     

Comparison of 1,2-propanediol and ethylene glycol for cryopreservation of slow-cooled mouse zygotes and their subsequent development

Purpose : This study was conducted on cryoprotective activity of ethylene glycol (ETG) and propanediol (PROH) on cleavage rate of mouse zygotes. Methods : Mouse oocytes were excised from fallopian tube of gonadotropin-treated mice, then inseminated with spermatozoa. After 16.5–17.5 h, zygotes were randomly allocated into three groups; control, toxicity, and frozen. In the latter, zygotes were slowly cooled with ETG and PROH similar to those used for human embryo cryopreservation. The survived zygotes cultured for 120 h and their later stages of development were compared with nonfrozen embryos. Results : The toxicity test showed that no differences were observed in cleavage rate between exposed and nonexposed embryos. The survival and expanded hatching blastocyst rate of embryos frozen with PROH was significantly better than with ETG (92.8 vs. 58.2% and 68.2 vs. 39.1%, respectively). Conclusions : ETG does not appear to be a good alternative to the classical PROH for freezing of mouse zygotes.     

Inverse relationship between the contents of neuromelanin pigment and the vesicular monoamine transporter-2: human midbrain dopamine neurons

The dopaminergic neurons in the ventral substantia nigra (SN) are significantly more vulnerable to degeneration in Parkinson's disease (PD) than the dopaminergic neurons in the ventral tegmental area (VTA). The ventral SN neurons also contain significantly more neuromelanin pigment than the dopaminergic neurons in the VTA. In vitro data indicate that neuromelanin pigment is formed from the excess cytosolic catecholamine that is not accumulated into synaptic vesicles by the vesicular monoamine transporter-2 (VMAT2). By using quantitative immunohistochemical methods in human postmortem brain, we sought to examine the relative contents of VMAT2 within neurons that contain different amounts of neuromelanin pigment. The immunostaining intensity (ISI) was measured for VMAT2 and also for the rate-limiting enzyme for the synthesis of dopamine, tyrosine hydroxylase (TH). ISI measures were taken from the ventral SN region where neurons are most vulnerable to degeneration in PD, nigrosome-1 (N1); from the ventral SN region where cells are moderately vulnerable to degeneration in PD, the matrix (M); and from VTA neurons near the exit of the third nerve (subregion III). The data indicate that 1) subregion III neurons have significantly higher levels of VMAT2 ISI compared with N1 neurons (more than twofold) and M neurons (45%); 2) there is an inverse relationship between VMAT2 ISI and neuromelanin pigment in the N1 and III neurons; 3) there is an inverse relationship between VMAT2 ISI and the vulnerability to degeneration in PD in the N1, M, and III subregions; and 4) neurons with high VMAT2 ISI also have high TH ISI. These data support the hypothesis that midbrain dopaminergic neurons that synthesize greater amounts of dopamine have more vesicular storage capacity for action potential-induced release of transmitter and that the ventral SN neurons accumulate the most neuromelanin pigment, in part because they have the least VMAT2 protein.     

Astrocyte ablation induced by La-aminoadipate (L-AAA) potentiates remyelination in a cuprizone demyelinating mouse model

Metabolic Brain Disease - Chronic demyelination in the central nervous system (CNS) is accompanied by an increase in the number of reactive astrocytes and astrogliosis. There are controversial...     

Cholinergic neuropathology in a mouse model of Alzheimer's disease

Transgenic mice overexpressing mutant human amyloid precursor protein (PDAPP mice) develop several Alzheimer's disease (AD)-like lesions including an age-related accumulation of amyloid-beta (Abeta)-containing neuritic plaques. Although aged, heterozygous PDAPP mice also exhibit synaptic and glial cell changes characteristic of AD pathology, no evidence of widespread neuronal loss has been observed. The present study sought to determine whether homozygous PDAPP mice, which express very high levels of Abeta peptide, exhibit AD-like cholinergic degenerative changes, and whether the changes parallel the deposition of Abeta plaques. Mice were examined at 2 and 4 months and at 1 and 2 years of age. There was an age-related increase in the density of Abeta plaques in the cortex and hippocampus of the PDAPP animals; at 4 months of age there were very few plaques, and at 2 years there was a very high density of plaques. There was an age-related reduction in the density of cholinergic nerve terminals in the cerebral cortex; at 2 months there was a normal density of nerve terminals, but as early as age 4 months there was an approximately 50% reduction. However, at age 2 years there was no difference in the number or size of basal forebrain cholinergic somata compared with 2-month-old PDAPP mice. These data indicated that the homozygous PDAPP mouse exhibits cholinergic nerve terminal degenerative pathology and that the cortical neurodegenerative changes occur before the deposition of Abeta-containing neuritic plaques.     

Regulatory effect of triiodothyronine on brain myelination and astrogliosis after cuprizone-induced demyelination in mice

Metabolic Brain Disease - Chronic demyelination and plaque formation in multiple sclerosis is accompanied by persisting astrogliosis, negatively influencing central nervous system recovery and...     

Synthesis of calcium carbonate microcapsules as self-healing containers

Contemporary studies of self-healing polymer composites are based on microcapsules synthesized using synthetic and toxic polymers, biopolymers, etc. via methods such as in situ polymerization, electrospraying, and air atomization. Herein, we synthesized a healing agent, epoxy (EPX) encapsulated calcium carbonate (CC) microcapsules, which was used to prepare self-healing EPX composites as a protective coating for metals. The CC microcapsules were synthesized using two facile methods, namely, the soft-template method (STM) and the in situ emulsion method (EM). Microcapsules prepared using the STM (ST-CC) were synthesized using sodium dodecyl sulphate (SDS) surfactant micelles as the soft-template, while the microcapsules prepared using the EM (EM-CC) were synthesized in an oil-in-water (O/W) in situ emulsion. These prepared CC microcapsules were characterized using light microscopy (LMC), field emission scanning electron microscopy (FE-SEM), fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), and thermogravimetric analysis (TGA). The synthesized ST-CC microcapsules were spherical in shape, with an average diameter of 2.5 μm and an average shell wall thickness of 650 nm, while EM-CC microcapsules had a near-spherical shape with an average diameter of 3.4 μm and an average shell wall thickness of 880 nm. The ST-CC capsules exhibited flake-like rough surfaces while EM-CC capsules showed smooth bulgy surfaces. The loading capacity of ST-CC and EM-CC microcapsules were estimated using TGA and found to be 11% and 36%, respectively. The FTIR and NMR spectra confirmed the EPX encapsulation and the unreactive nature of the loaded EPX with the inner walls of CC microcapsules. The synthesized CC microcapsules were further incorporated into an EPX matrix to prepare composite coatings with 10 (w/w%), 20 (w/w%), and 50 (w/w%) capsule loadings. The prepared EPX composite coatings were scratched and observed using FE-SEM and LMC to evaluate the release of encapsulated EPX inside the CC capsules, which is analogous to the healing behaviour. Moreover, EPX composite coatings with 20 (w/w%) and 50 (w/w%) of ST-CC showed better healing performances. Thus, it was observed that ST-CC microcapsules outperformed EM-CC. Additionally, the EPX/CC coatings showed remarkable self-healing properties by closing the gaps of the scratch surfaces. Thus, these formaldehyde-free, biocompatible, biodegradable, and non-toxic CC based EPX composite coatings hold great potential to be used as a protective coating for metal substrates. Primary results detected significant corrosion retardancy due to the self-healing coatings under an accelerated corrosion process, which was performed with a salt spray test.

Healing agent, epoxy encapsulated calcium carbonate microcapsules were prepared using a facile method as a self-healing composite for protective metal coatings.