Open Access. Powered by Scholars. Published by Universities.®

Laboratory and Basic Science Research Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 6 of 6

Full-Text Articles in Laboratory and Basic Science Research

Microglia-Neuron Interactions In A Mouse Model Of Low Grade Neuroepithelial Tumors, Veolette Hanna May 2020

Microglia-Neuron Interactions In A Mouse Model Of Low Grade Neuroepithelial Tumors, Veolette Hanna

Honors Scholar Theses

Microglia are the macrophages of the brain and spinal cord, playing an important role in the immune response to disease states of the nervous system. This study conducts an investigation on the activity of microglia in response to low grade neuroepithelial tumors. Using mouse models and microglial markers, a qualitative and quantitative analysis of microglia activation, migration, and invasion within the brain cortex during early stages of tumor development was conducted. It was found that the presence of a low grade neuroepithelial tumor in the cortex of one hemisphere of the brain causes significant microglia activation in comparison to the …


A Catalog Of Scn1a Variants, Christoph Lossin Dec 2008

A Catalog Of Scn1a Variants, Christoph Lossin

Christoph Lossin, Ph.D.

Over the past 10 years mutations in voltage-gated sodium channels (Navs) have become closely associated with inheritable forms of epilepsy. One isoform in particular, Nav1.1 (gene symbol SCN1A), appears to be a superculprit, registering with more than 330 mutations to date. The associated phenotypes range from benign febrile seizures to extremely serious conditions, such as Dravet’s syndrome (SMEI). Despite the wealth of information, mutational analyses are cumbersome, owing to inconsistencies among the Nav1.1 sequences to which different research groups refer. Splicing variability is the core problem: Nav1.1 co-exists in three isoforms, two of them lack 11 or 28 amino acids …


Single-Channel Properties Of Human Nav1.1 And Mechanism Of Channel Dysfunction In Scn1a-Associated Epilepsy, C. Vanoye, Christoph Lossin, T. H. Rhodes, Alfred L. George Dec 2004

Single-Channel Properties Of Human Nav1.1 And Mechanism Of Channel Dysfunction In Scn1a-Associated Epilepsy, C. Vanoye, Christoph Lossin, T. H. Rhodes, Alfred L. George

Christoph Lossin, Ph.D.

Mutations in genes encoding neuronal voltage-gated sodium channel subunits have been linked to inherited forms of epilepsy. The majority of mutations (>100) associated with generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI) occur in SCN1A encoding the NaV1.1 neuronal sodium channel alpha-subunit. Previous studies demonstrated functional heterogeneity among mutant SCN1A channels, revealing a complex relationship between clinical and biophysical phenotypes. To further understand the mechanisms responsible for mutant SCN1A behavior, we performed a comprehensive analysis of the single-channel properties of heterologously expressed recombinant WT-SCN1A channels. Based on these data, we then determined the …


Non-Inactivating Voltage-Gated Sodium Channels In Severe Myoclonic Epilepsy Of Infancy, T. H. Rhodes, Christoph Lossin, C. Vanoye, Alfred L. George Jan 2004

Non-Inactivating Voltage-Gated Sodium Channels In Severe Myoclonic Epilepsy Of Infancy, T. H. Rhodes, Christoph Lossin, C. Vanoye, Alfred L. George

Christoph Lossin, Ph.D.

Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel alpha(1) subunit (Na(V)1.1), are associated with at least two forms of epilepsy, generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy of infancy (SMEI). We examined the functional properties of five SMEI mutations by using whole-cell patch-clamp analysis of heterologously expressed recombinant human SCN1A. Two mutations (F902C and G1674R) rendered SCN1A channels nonfunctional, and a third allele (G1749E) exhibited minimal functional alterations. However, two mutations within or near the S4 segment of the fourth repeat domain (R1648C and F1661S) conferred significant impairments in fast inactivation, including persistent, noninactivating …


Epilepsy-Associated Dysfunction In The Voltage-Gated Neuronal Sodium Channel Scn1a, Christoph Lossin, T. Rhodes, R. Desai, C. Vanoye, S. Caniciu, O. Devinsky, A. George Dec 2003

Epilepsy-Associated Dysfunction In The Voltage-Gated Neuronal Sodium Channel Scn1a, Christoph Lossin, T. Rhodes, R. Desai, C. Vanoye, S. Caniciu, O. Devinsky, A. George

Christoph Lossin, Ph.D.

Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel subunit (Nav1.1) are associated with at least two forms of epilepsy, generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). We examined the functional properties of four GEFS+ alleles and one SMEI allele using whole-cell patch-clamp analysis of heterologously expressed recombinant human SCN1A. One previously reported GEFS+ mutation (I1656M) and an additional novel allele (R1657C), both affecting residues in a voltage-sensing S4 segment, exhibited a similar depolarizing shift in the voltage dependence of activation. Additionally, R1657C showed a 50% reduction in current density and …


Molecular Basis Of An Inherited Epilepsy, Christoph Lossin, T. H. Rhodes, C. Vanoye, D. Wang, Alfred L. George Dec 2001

Molecular Basis Of An Inherited Epilepsy, Christoph Lossin, T. H. Rhodes, C. Vanoye, D. Wang, Alfred L. George

Christoph Lossin, Ph.D.

Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel alpha1 subunit (NaV1.1), are associated with at least two forms of epilepsy, generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). We examined the functional properties of four GEFS+ alleles and one SMEI allele using whole-cell patch-clamp analysis of heterologously expressed recombinant human SCN1A. One previously reported GEFS+ mutation (I1656M) and an additional novel allele (R1657C), both affecting residues in a voltage-sensing S4 segment, exhibited a similar depolarizing shift in the voltage dependence of activation. Additionally, R1657C showed a 50% reduction in current density …