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Calpain Inhibitor Mdl28170 Modulates Abeta Formation By Inhibiting The Formation Of Intermediate Abeta46 And Protecting Abeta From Degradation, Y Dong, J Tan, Mei-Zhen Cui, G Zhao, G Mao, N Singh, Xuemin Xu Jun 2013

Calpain Inhibitor Mdl28170 Modulates Abeta Formation By Inhibiting The Formation Of Intermediate Abeta46 And Protecting Abeta From Degradation, Y Dong, J Tan, Mei-Zhen Cui, G Zhao, G Mao, N Singh, Xuemin Xu

Mei-Zhen Cui

The observations that three major cleavages within the transmembrane domain of APP, namely, the gamma-cleavage, -cleavage, and the newly identified zeta-cleavage, are involved in the generation of secreted Abeta40 and Abeta42 prompted us to determine how the calpain inhibitor III MDL 28170 influences these three cleavages and Abeta formation. With the use of a cell culture system, our data demonstrate that 1) at either high concentrations, or at a low range of concentrations, at early time points, MDL 28170 inhibits the formation of secreted Abeta40 and Abeta42. However, this effect is due to inhibition of the intermediate Abeta46 generation by ...


Serotonergic Pre-Treatments Block In Vitro Serotonergic Phase Shifts Of The Mouse Suprachiasmatic Nucleus Circadian Clock, Rebecca Prosser, H. Lee, A. Wehner Sep 2006

Serotonergic Pre-Treatments Block In Vitro Serotonergic Phase Shifts Of The Mouse Suprachiasmatic Nucleus Circadian Clock, Rebecca Prosser, H. Lee, A. Wehner

Rebecca Prosser

The suprachiasmatic nucleus (SCN) contains a circadian clock that maintains its time-generating and phase-modulating capacities in vitro. Previous studies report clear differences in the ability of serotonergic stimuli to phase-shift the SCN clock when applied directly to the SCN either in vivo or in vitro: while mice and rat circadian clocks are readily phase-shifted by serotonin (5-HT) or 5-HT agonists applied in vitro, hamster and mice circadian clocks respond inconsistently to 5-HT agonists injected directly into the SCN in vivo. Here we have investigated one possible explanation for these differences: that the SCN isolated in vitro experiences reduced endogenous 5-HT ...


Neuroprotective And Disease-Modifying Effects Of The Ketogenic Diet, Maciej Gasior, Michael A. Rogawski, Adam L. Hartman Aug 2006

Neuroprotective And Disease-Modifying Effects Of The Ketogenic Diet, Maciej Gasior, Michael A. Rogawski, Adam L. Hartman

Michael A. Rogawski

The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models ...


Diverse Mechanisms Of Antiepileptic Drugs In The Development Pipeline, Michael A. Rogawski Jun 2006

Diverse Mechanisms Of Antiepileptic Drugs In The Development Pipeline, Michael A. Rogawski

Michael A. Rogawski

There is a remarkable array of new chemical entities in the current antiepileptic drug (AED) development pipeline. In some cases, the compounds were synthesized in an attempt improve upon the activity of marketed AEDs. In other cases, the discovery of antiepileptic potential was largely serendipitous. Entry into the pipeline begins with the demonstration of activity in one or more animal screening models. Results from testing in a panel of such models provide a basis to differentiate agents and may offer clues as to the mechanism. Target activity may then be defined through cell-based studies, often years after the initial identification ...


Lysophosphatidic Acid Induces Early Growth Response Gene 1 Expression In Vascular Smooth Muscle Cells: Cre And Sre Mediate The Transcription, Mei-Zhen Cui, E Laag, L Sun, M Tan, G Zhao, Xuemin Xu Apr 2006

Lysophosphatidic Acid Induces Early Growth Response Gene 1 Expression In Vascular Smooth Muscle Cells: Cre And Sre Mediate The Transcription, Mei-Zhen Cui, E Laag, L Sun, M Tan, G Zhao, Xuemin Xu

Xuemin Xu

OBJECTIVE: Lysophosphatidic acid (LPA), one component of oxidized low-density lipoprotein, is a potent bioactive phospholipid. Early growth response gene-1 (Egr-1), an important transcription factor, regulates expression of an array of genes involved in vascular diseases. Whether and how LPA regulates the transcriptional machinery of Egr-1 gene is unknown and is addressed in this study. METHOD AND RESULTS: We found that LPA markedly induces Egr-1 mRNA and protein in aortic smooth muscle cells (SMCs). RNA stability and nuclear run-on assays reveal that LPA-induced Egr-1 gene expression is controlled at the transcriptional level. Reporter gene analyses have shown that the -141 to ...


Activation In Neural Networks Controlling Ingestive Behaviors: What Does It Mean, And How Do We Map And Measure It?, Alan G. Watts, Arshad M. Khan, Graciela Sanchez-Watts, Dawna Salter, Christina M. Neuner Apr 2006

Activation In Neural Networks Controlling Ingestive Behaviors: What Does It Mean, And How Do We Map And Measure It?, Alan G. Watts, Arshad M. Khan, Graciela Sanchez-Watts, Dawna Salter, Christina M. Neuner

Arshad M. Khan, Ph.D.

No abstract provided.


Activation Of Protein Kinase C Zeta By Peroxynitrite Regulates Lkb1-Dependent Amp-Activated Protein Kinase In Cultured Endothelial Cells, Z Xie, Y Dong, M Zhang, Mei Cui, R Cohen, U Riek, D Neumann, U Schlattner, M Zou Mar 2006

Activation Of Protein Kinase C Zeta By Peroxynitrite Regulates Lkb1-Dependent Amp-Activated Protein Kinase In Cultured Endothelial Cells, Z Xie, Y Dong, M Zhang, Mei Cui, R Cohen, U Riek, D Neumann, U Schlattner, M Zou

Mei-Zhen Cui

We previously reported the phosphoinositide 3-kinase-dependent activation of the 5'-AMP-activated kinase (AMPK) by peroxynitrite (ONOO-) and hypoxia-reoxygenation in cultured endothelial cells. Here we show the molecular mechanism of activation of this pathway. Exposure of bovine aortic endothelial cells to ONOO- significantly increased the phosphorylation of both Thr172 of AMPK and Ser1179 of endothelial nitric-oxide synthase, a known downstream enzyme of AMPK. In addition, activation of AMPK by ONOO- was accompanied by increased phosphorylation of protein kinase Czeta (PKCzeta) (Thr410/403) and translocation of cytosolic PKCzeta into the membrane. Further, inhibition of PKCzeta abrogated ONOO- -induced AMPK-Thr172 phosphorylation as that ...


Calpain Inhibitor Mdl28170 Modulates Abeta Formation By Inhibiting The Formation Of Intermediate Abeta46 And Protecting Abeta From Degradation, Y Dong, J Tan, Mei-Zhen Cui, G Zhao, G Mao, N Singh, Xuemin Xu Jan 2006

Calpain Inhibitor Mdl28170 Modulates Abeta Formation By Inhibiting The Formation Of Intermediate Abeta46 And Protecting Abeta From Degradation, Y Dong, J Tan, Mei-Zhen Cui, G Zhao, G Mao, N Singh, Xuemin Xu

Xuemin Xu

The observations that three major cleavages within the transmembrane domain of APP, namely, the gamma-cleavage, -cleavage, and the newly identified zeta-cleavage, are involved in the generation of secreted Abeta40 and Abeta42 prompted us to determine how the calpain inhibitor III MDL 28170 influences these three cleavages and Abeta formation. With the use of a cell culture system, our data demonstrate that 1) at either high concentrations, or at a low range of concentrations, at early time points, MDL 28170 inhibits the formation of secreted Abeta40 and Abeta42. However, this effect is due to inhibition of the intermediate Abeta46 generation by ...


Cognitive-Vestibular Interactions: A Review Of Patient Difficulties And Possible Mechanisms, Douglas Hanes, Gin Mccollum Jan 2006

Cognitive-Vestibular Interactions: A Review Of Patient Difficulties And Possible Mechanisms, Douglas Hanes, Gin Mccollum

Gin McCollum

Cognitive deficits such as poor concentration and short-term memory loss are known by clinicians to occur frequently among patients with vestibular abnormalities. Although direct scientific study of such deficits has been limited, several types of investigations do lend weight to the existence of vestibular-cognitive effects. In this article we review a wide range of studies indicating a vestibular influence on the ability to perform certain cognitive functions. In addition to tests of vestibular patient abilities, these studies include dual-task studies of cognitive and balance functions, studies of vestibular contribution to spatial perception and memory, and works demonstrating a vestibular influence ...


Mental Retardation: A Mri Study Of 146 Brazilian Children, Armando F. Rocha, Cláudia C. Leite, Fábio T. Rocha Jan 2006

Mental Retardation: A Mri Study Of 146 Brazilian Children, Armando F. Rocha, Cláudia C. Leite, Fábio T. Rocha

Armando F Rocha

We report results of a magnetic ressonance imaging (MRI) study of 146 Brazilian children, whose intelligence quotient scored less than 70. 50% of MRI examinations did not exhibit any signal of structural lesion (N group), whereas a focal thinning at the junction of the body and splenium of the corpus callosum; ventricular asymmetry; periventricular leukomalacia; gliosis and arachnoid cysts were among the most frequent findings in the remaining of subjects (L group). Maternal stress and altered blood pre ss u re were the most frequent findings in the pre-natal history of both N and L children. Familial antecedents of mental ...


Identifying Placebo Effects With Data From Clinical Trials, Anup Malani Jan 2006

Identifying Placebo Effects With Data From Clinical Trials, Anup Malani

Anup Malani

A medical treatment is said to have placebo effects if patients who are optimistic about the treatment respond better to the treatment. This paper proposes a simple test for placebo effects. Instead of comparing the treatment and control arms of a single trial, one should compare the treatment arms of two trials with different probabilities of assignment to treatment. If there are placebo effects, patients in the higher-probability trial will experience better outcomes simply because they believe that there is a greater chance of receiving treatment. This paper finds evidence of placebo effects in trials of antiulcer and cholesterol-lowering drugs.


Functional Connectivity In A Baseline Resting-State Network In Autism, Vladimir Cherkassky, Rajesh Kana, Timothy Keller, Marcel Just Dec 2005

Functional Connectivity In A Baseline Resting-State Network In Autism, Vladimir Cherkassky, Rajesh Kana, Timothy Keller, Marcel Just

Marcel Adam Just

No abstract provided.


Head Tilt-Translation Combinations Distinguished At The Level Of Neurons, Jan E. Holly, Sarah E. Pierce, Gin Mccollum Dec 2005

Head Tilt-Translation Combinations Distinguished At The Level Of Neurons, Jan E. Holly, Sarah E. Pierce, Gin Mccollum

Gin McCollum

Angular and linear accelerations of the head occur throughout everyday life, whether from external forces such as in a vehicle or from volitional head movements. The relative timing of the angular and linear components of motion differs depending on the movement. The inner ear detects the angular and linear components with its semicircular canals and otolith organs, respectively, and secondary neurons in the vestibular nuclei receive input from these vestibular organs. Many secondary neurons receive both angular and linear input. Linear information alone does not distinguish between translational linear acceleration and angular tilt, with its gravity-induced change in the linear ...


Neuroscholar’S Electronic Laboratory Notebook And Its Application To Neuroendocrinology, Arshad M. Khan, Joel D. Hahn, We-Cheng Cheng, Alan G. Watts, Gully Apc Burns Dec 2005

Neuroscholar’S Electronic Laboratory Notebook And Its Application To Neuroendocrinology, Arshad M. Khan, Joel D. Hahn, We-Cheng Cheng, Alan G. Watts, Gully Apc Burns

Arshad M. Khan, Ph.D.

No abstract provided.


Brain Correlates Of Discourse Processing: An Fmri Investigation Of Irony And Conventional Metaphor Comprehension, Zohar Eviatar, Marcel Adam Just Dec 2005

Brain Correlates Of Discourse Processing: An Fmri Investigation Of Irony And Conventional Metaphor Comprehension, Zohar Eviatar, Marcel Adam Just

Marcel Adam Just

No abstract provided.


Alcohol Withdrawal Seizures, Michael A. Rogawski, Prosper N'Gouemo Dec 2005

Alcohol Withdrawal Seizures, Michael A. Rogawski, Prosper N'Gouemo

Michael A. Rogawski

No abstract provided.


Sentence Comprehension In Autism: Thinking In Pictures With Decreased Functional Connectivity, Rajesh K. Kana, Timothy A. Keller, Vladimir L. Cherkassky, Nancy J. Minshew, Marcel Adam Just Dec 2005

Sentence Comprehension In Autism: Thinking In Pictures With Decreased Functional Connectivity, Rajesh K. Kana, Timothy A. Keller, Vladimir L. Cherkassky, Nancy J. Minshew, Marcel Adam Just

Marcel Adam Just

No abstract provided.


Neural Basis Of Dyslexia: A Comparison Between Dyslexic And Non-Dyslexic Children Equated For Reading Ability, Fumiko Hoeft, Arvel Hernandez, Glenn Mcmillon, Heather Taylor-Hill, Jennifer L. Martindale, Ann Meyler, Timothy A. Keller, Wai Ting Siok, Gayle K. Deutsch, Marcel Adam Just, Susan Whitfield-Gabrieli, John D. E. Gabrieli Dec 2005

Neural Basis Of Dyslexia: A Comparison Between Dyslexic And Non-Dyslexic Children Equated For Reading Ability, Fumiko Hoeft, Arvel Hernandez, Glenn Mcmillon, Heather Taylor-Hill, Jennifer L. Martindale, Ann Meyler, Timothy A. Keller, Wai Ting Siok, Gayle K. Deutsch, Marcel Adam Just, Susan Whitfield-Gabrieli, John D. E. Gabrieli

Marcel Adam Just

No abstract provided.


Auditory Inhibitory Gating In Medial Prefrontal Cortex: Single Unit And Local Field Potential Analysis, Howard C. Cromwell Dec 2005

Auditory Inhibitory Gating In Medial Prefrontal Cortex: Single Unit And Local Field Potential Analysis, Howard C. Cromwell

Howard Casey Cromwell

Medial prefrontal cortex is a crucial region involved in inhibitory processes. Damage to the medial prefrontal cortex can lead to loss of normal inhibitory control over motor, sensory, emotional and cognitive functions. The goal of the present study was to examine the basic properties of inhibitory gating in this brain region in rats. Inhibitory gating has recently been proposed as a neurophysiological assay for sensory filters in higher brain regions that potentially enable or disable information throughput. This perspective has important clinical relevance due to the findings that gating is dramatically impaired in individuals with emotional and cognitive impairments (i ...


From Faculty For Undergraduate Neuroscience: Encouraging Innovation In Undergraduate Neuroscience Education By Supporting Student Research And Faculty Development, Eric Wiertelak, J. C. Hardwick, M. Kerchner, B. Lom, J. J. Ramirez Dec 2005

From Faculty For Undergraduate Neuroscience: Encouraging Innovation In Undergraduate Neuroscience Education By Supporting Student Research And Faculty Development, Eric Wiertelak, J. C. Hardwick, M. Kerchner, B. Lom, J. J. Ramirez

Eric Wiertelak

No abstract provided.


Unlimited Access To Heroin Self-Administration: Independent Motivational Markers Of Opiate Dependence, Laura O'Dell Dec 2005

Unlimited Access To Heroin Self-Administration: Independent Motivational Markers Of Opiate Dependence, Laura O'Dell

Laura Elena O'Dell

No abstract provided.


Behavioral And Neurochemical Responses To Cocaine In Periadolescent And Adult Rats, Laura O'Dell Dec 2005

Behavioral And Neurochemical Responses To Cocaine In Periadolescent And Adult Rats, Laura O'Dell

Laura Elena O'Dell

No abstract provided.


Biphasic Alterations In Serotonin1b (5-Ht1b) Receptor Function During Abstinence From Extended Cocaine Self-Administration, Laura O'Dell Dec 2005

Biphasic Alterations In Serotonin1b (5-Ht1b) Receptor Function During Abstinence From Extended Cocaine Self-Administration, Laura O'Dell

Laura Elena O'Dell

No abstract provided.


Diminished Nicotine Withdrawal In Adolescent Rats: Implications For Vulnerability To Addiction, Laura O'Dell Dec 2005

Diminished Nicotine Withdrawal In Adolescent Rats: Implications For Vulnerability To Addiction, Laura O'Dell

Laura Elena O'Dell

No abstract provided.


Extended Access To Nicotine Self-Administration Leads To Dependence: Circadian Measures, Withdrawal Measures, And Extinction Behavior In Rats, Laura O'Dell Dec 2005

Extended Access To Nicotine Self-Administration Leads To Dependence: Circadian Measures, Withdrawal Measures, And Extinction Behavior In Rats, Laura O'Dell

Laura Elena O'Dell

No abstract provided.


Corticotropin-Releasing Factor Within The Central Nucleus Of The Amygdala Mediates Enhanced Ethanol Self-Administration In Ethanol-Dependent Rats During Withdrawal., Laura O'Dell Dec 2005

Corticotropin-Releasing Factor Within The Central Nucleus Of The Amygdala Mediates Enhanced Ethanol Self-Administration In Ethanol-Dependent Rats During Withdrawal., Laura O'Dell

Laura Elena O'Dell

No abstract provided.