Measurements Of Long-term Potentiation Research Articles

Tuning of hydrophobicity of WO3-based hot-dip zinc coating with improved self-cleaning and anti-corrosion properties

Hot-dip galvanic (ZnAl) coatings with enhanced self-cleaning and anti-corrosion attributes were developed through effective incorporation of WO3 nanoparticles. The wet-synthesized WO3 nanoparticles were systematically characterized for crystallinity, optical properties, bonding characteristics, compositional purity, chemical state, morphology, size distribution, and colloidal and thermal stability; and successfully assimilated into the galvanic coating. High water contact angles (112.3°) recorded for the composite coating revealed improved hydrophobicity of the tuned surface. The coating displayed excellent self-cleaning property against the applied dirt particles. The hydrophobic WO3 nanoparticles-incorporated coating exhibited superior anti-corrosion performance than the conventional bare ZnAl coating as revealed by scanning Kelvin probe microscopic studies, long-term potential measurements, Tafel polarization and impedance spectroscopy. The composite coating exhibited high charge transfer resistance (280.20 Ω.cm2) and low corrosion rate (6.54 × 10−6 mmpy) along with enhanced mechanical and tribological properties. The better performance of the composite coating was attributed to the combined ‘barrier-hydrophobic-sacrificial’ effect of the WO3-incorporated ZnAl coating.

Effects of dietary 5-methoxyindole-2-carboxylic acid on brain functional recovery after ischemic stroke

Stroke leads to devastating outcomes including impairments of sensorimotor and cognitive function that may be long lasting. New intervention strategies are needed to overcome the long-lasting effects of ischemic injury. Previous studies determined that treatment with 5-methoxyindole-2-carboxylic acid (MICA) conferred chemical preconditioning and neuroprotection against stroke. The purpose of the current study was to determine whether the preconditioning can lead to functional improvements after stroke (done by transient middle cerebral artery occlusion). After 4 weeks of MICA feeding, half the rats underwent ischemic injury, while the other half remained intact. After one week recovery, all the rats were tested for motor and cognitive function (rotorod and water maze). At the time of euthanasia, measurements of long-term potentiation (LTP) were performed. While stroke injury led to motor and cognitive dysfunction, MICA supplementation did not reverse these impairments. However, MICA supplementation did improve stroke-related impairments in hippocampal LTP. The dichotomy of the outcomes suggest that more studies are needed to determine optimum duration and dosage for MICA to lead to substantial motor and cognitive improvements, along with LTP change and neuroprotection.

Altered Behavior in Mice Socially Isolated During Adolescence Corresponds With Immature Dendritic Spine Morphology and Impaired Plasticity in the Prefrontal Cortex.

Mice socially isolated during adolescence exhibit behaviors of anxiety, depression and impaired social interaction. Although these behaviors are well documented, very little is known about the associated neurobiological changes that accompany these behaviors. It has been hypothesized that social isolation during adolescence alters the development of the prefrontal cortex, based on similar behavioral abnormalities observed in isolated mice and those with disruption of this structure. To establish relationships between behavior and underlying neurobiological changes in the prefrontal cortex, Thy-1-GFP mice were isolated from weaning until adulthood and compared to group-housed littermates regarding behavior, electrophysiological activity and dendritic morphology. Results indicate an immaturity of dendritic spines in single housed animals, with dendritic spines appearing smaller and thinner. Single housed mice additionally show impaired plasticity through measures of long-term potentiation. Together these findings suggest an altered development and impairment of the prefrontal cortex of these animals underlying their behavioral characteristics.

N-Terminal Hypothesis for Alzheimer's Disease.

Although the amyloid (abeta peptide, Aβ) hypothesis is 25 years old, is the dominant model of Alzheimer's disease (AD) pathogenesis, and guides the development of potential treatments, it is still controversial. One possible reason is a lack of a mechanistic path from the cleavage products of the amyloid precursor protein (APP) such as soluble Aβ monomer and soluble molecular fragments to the deleterious effects on synaptic form and function. From a review of the recent literature and our own published work including aggregation kinetics and structural morphology, Aβ clearance, molecular simulations, long-term potentiation measurements with inhibition binding, and the binding of a commercial monoclonal antibody, aducanumab, we hypothesize that the N-terminal domains of neurotoxic Aβ oligomers are implicated in causing the disease.

Hirano body expression impairs spatial working memory in a novel mouse model.

IntroductionHirano bodies are actin-rich intracellular inclusions found in the brains of patients with neurodegenerative conditions such as Alzheimer's disease or frontotemporal lobar degeneration-tau. While Hirano body ultrastructure and protein composition have been well studied, little is known about the physiological function of Hirano bodies in an animal model system.ResultsUtilizing a Cre/Lox system, we have generated a new mouse model which develops an age-dependent increase in the number of model Hirano bodies present in both the CA1 region of the hippocampus and frontal cortex. These mice develop normally and experience no overt neuron loss. Mice presenting model Hirano bodies have no abnormal anxiety or locomotor activity as measured by the open field test. However, mice with model Hirano bodies develop age-dependent impairments in spatial working memory performance assessed using a delayed win-shift task in an 8-arm radial maze. Synaptic transmission, short-term plasticity, and long-term plasticity was measured in the CA1 region from slices obtained from both the ventral and dorsal hippocampus in the same mice whose spatial working memory was assessed. Baseline synaptic responses, paired pulse stimulation and long-term potentiation measurements in the ventral hippocampus were indistinguishable from control mice. In contrast, in the dorsal hippocampus, synaptic transmission at higher stimulus intensities were suppressed in 3 month old mice with Hirano bodies as compared with control mice. In addition, long-term potentiation was enhanced in the dorsal hippocampus of 8 month old mice with Hirano bodies, concurrent with observed impairment of spatial working memory. Finally, an inflammatory response was observed at 8 months of age in mice with Hirano bodies as assessed by the presence of reactive astrocytes.ConclusionThis study shows that the presence of model Hirano bodies initiates an inflammatory response, alters hippocampal synaptic responses, and impairs spatial working memory in an age-dependent manner. This suggests that Hirano bodies may promote disease progression. This new model mouse provides a tool to investigate how Hirano bodies interact with other pathologies associated with Alzheimer's disease. Hirano bodies likely play a complex and region specific role in the brain during neurodegenerative disease progression.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-014-0131-9) contains supplementary material, which is available to authorized users.

Oligomer-targeting with a conformational antibody fragment promotes toxicity in Aβ-expressing flies.

IntroductionThe self-assembly of Aβ peptides into a range of conformationally heterogeneous amyloid states represents a fundamental event in Alzheimer’s disease. Within these structures oligomeric intermediates are considered to be particularly pathogenic. To test this hypothesis we have used a conformational targeting approach where particular conformational states, such as oligomers or fibrils, are recognized in vivo by state-specific antibody fragments.ResultsWe show that oligomer targeting with the KW1 antibody fragment, but not fibril targeting with the B10 antibody fragment, affects toxicity in Aβ-expressing Drosophila melanogaster. The effect of KW1 is observed to occur selectively with flies expressing Aβ(1–40) and not with those expressing Aβ(1–42) or the arctic variant of Aβ(1–42) This finding is consistent with the binding preference of KW1 for Aβ(1–40) oligomers that has been established in vitro. Strikingly, and in contrast to the previously demonstrated in vitro ability of this antibody fragment to block oligomeric toxicity in long-term potentiation measurements, KW1 promotes toxicity in the flies rather than preventing it. This result shows the crucial importance of the environment in determining the influence of antibody binding on the nature and consequences of the protein misfolding and aggregation.ConclusionsWhile our data support to the pathological relevance of oligomers, they highlight the issues to be addressed when developing inhibitory strategies that aim to neutralize these states by means of antagonistic binding agents.

Hirano body expression impairs spatial working memory in a novel mouse model

IntroductionHirano bodies are actin-rich intracellular inclusions found in the brains of patients with neurodegenerative conditions such as Alzheimer's disease or frontotemporal lobar degeneration-tau. While Hirano body ultrastructure and protein composition have been well studied, little is known about the physiological function of Hirano bodies in an animal model system.ResultsUtilizing a Cre/Lox system, we have generated a new mouse model which develops an age-dependent increase in the number of model Hirano bodies present in both the CA1 region of the hippocampus and frontal cortex. These mice develop normally and experience no overt neuron loss. Mice presenting model Hirano bodies have no abnormal anxiety or locomotor activity as measured by the open field test. However, mice with model Hirano bodies develop age-dependent impairments in spatial working memory performance assessed using a delayed win-shift task in an 8-arm radial maze. Synaptic transmission, short-term plasticity, and long-term plasticity was measured in the CA1 region from slices obtained from both the ventral and dorsal hippocampus in the same mice whose spatial working memory was assessed. Baseline synaptic responses, paired pulse stimulation and long-term potentiation measurements in the ventral hippocampus were indistinguishable from control mice. In contrast, in the dorsal hippocampus, synaptic transmission at higher stimulus intensities were suppressed in 3 month old mice with Hirano bodies as compared with control mice. In addition, long-term potentiation was enhanced in the dorsal hippocampus of 8 month old mice with Hirano bodies, concurrent with observed impairment of spatial working memory. Finally, an inflammatory response was observed at 8 months of age in mice with Hirano bodies as assessed by the presence of reactive astrocytes.ConclusionThis study shows that the presence of model Hirano bodies initiates an inflammatory response, alters hippocampal synaptic responses, and impairs spatial working memory in an age-dependent manner. This suggests that Hirano bodies may promote disease progression. This new model mouse provides a tool to investigate how Hirano bodies interact with other pathologies associated with Alzheimer's disease. Hirano bodies likely play a complex and region specific role in the brain during neurodegenerative disease progression.

P 170. Characterization of brain plasticity in Diabetes Type II and Alzheimer’s disease supports link between both diseases

Introduction Increased incidence of Alzheimer’s disease (AD) in individuals with Diabetes Type II (DM2) suggests a possible pathophysiologic link. Support for such a link comes from several experimental animal models. Insulin deficiency and resistance are major factors in the pathogenesis of DM2 and appear to be involved in the neurodegenerative processes of AD by altering synaptic brain plasticity. Transcranial magnetic stimulation (TMS) can be used to examine mechanisms of plasticity, and may thus reveal abnormalities in patients with DM2 that might resemble those in patients with AD. Objectives Evaluate cortical plasticity mechanisms in subjects with DM2 and compare them with those in patients with AD as assessed by TMS measures. Explore possible similarities in abnormal brain plasticity in order to investigate the link between DM2 and AD. Materials and methods To evaluate cortical brain plasticity we applied intermittent theta burst stimulation (iTBS) at 80% of active motor threshold (aMT) over the left primary motor cortex (M1) in patients with mild to moderate AD, DM2 and in healthy individuals. iTBS consisted of a total of 600 pulses divided into 20 trains, each including bursts of 3 pulses at 50 Hz repeated at 5 Hz for 2 s and with an 8 s interval between trains. Motor evoked potentials (MEPs) of the right first dorsal interosseus muscle (FDI) were triggered by neuronavigated single pulse transcranial magnetic stimulation (spTMS) over left M1 at 120% of resting motor threshold (rMT) before and after iTBS. Changes in MEP amplitudes after iTBS were examined as measures of long term potentiation (LTP) like plasticity. Results Within the first 20 min following iTBS baseline corrected MEPs were significantly larger for healthy subjects (1.32 ± 0.21 mV) compared to patients with AD (0.92 ± 0.08 mV; p = 0.023) and DM2 (0.69 ± 0.15 mV; p = 0.007) (Fig. 1). There was no significant difference between AD and DM2 (p = 0.63). Interestingly, while iTBS had almost no effect on AD patients it tended to have a paradoxically inhibitory effect in patients with DM2. Conclusion The iTBS-induced modulation of corticospinal excitability is impaired in both AD and DM2. This finding supports the notion of aberrant LTP-like mechanisms of plasticity in DM2 and AD, and suggests a pathophysiologic link between the two diseases. This link may account for the epidemiologically increased risk for patients with DM2 to develop AD. Further studies and longitudinal assessments are needed to explore such a link further, but in this context, TMS-methods appear promising and may become a valuable early biomarker for AD and individuals at risk. Acknowledgements The study was sponsored and supported by the Harvard Catalyst, Nexstim, Neuronix Ltd., the National Institutes of Health, and the Berenson-Allen Foundation. Download : Download high-res image (60KB) Download : Download full-size image