Author Of 2 Presentations

Biostatistical Methods Poster Presentation

P0001 - A new software and analysis suite for experimental autoimmune encephalomyelitis (ID 831)

Speakers
Presentation Number
P0001
Presentation Topic
Biostatistical Methods

Abstract

Background

Experimental Autoimmune Encephalomyelitis (EAE) is the most widely used multiple sclerosis animal model. In this model, animals develop an autoimmune inflammatory immune response to myelin protein leading to the development of ascending paralysis. The degree of motor dysfunction is scored daily and used as a metric of disease progression referred to as EAE disease score. Despite the common use of EAE animal models, there is still a large degree of heterogeneity in the field on EAE disease score data presentation and statistical assessment, making it challenging to compare results across studies.

Objectives

In an effort to standardize EAE disease score assessment, our objective was to develop an easy to use web-based application and associated package that provides researchers with a user interface for graphing and conducting statistical analysis of their data.

Methods

Using the programming language R, a shiny based application was developed to provide users with an interface to process their EAE data. For statistical testing, the application was flexibly designed to allow for parametric and non-parametric testing paradigms in addition to a number of different p-value correction methods.

Results

Our application uses a multifaceted analysis including EAE score curves (graphing EAE disease scores by group over time), area under the curve, Poisson modeling of frequency of days over a score threshold, and hierarchical clustering with a unique option of aligning animals by the day of disease onset. With this tool, researchers can quickly analyze their EAE data without code from the user while still maintaining a wide degree of flexibility in graphic and models parameters.

Conclusions

We have developed an application and an accompanying package that can be used quickly and easily to generate results for EAE disease score analysis. In the application, a user-friendly interface designed specifically for EAE models helps researchers assess their data by auto-generating graphs and statistical tests in a fast reproducible manner. We hope that this application and its analyses will assist researchers while initiating discussion and moving towards a field standard of EAE data presentation and analysis.

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Gender Differences, Hormones and Sex Chromosomes Poster Presentation

P1116 - Binge alcohol consumption in murine models of Multiple Sclerosis leads to sex-specific disease development.  (ID 1768)

Speakers
Presentation Number
P1116
Presentation Topic
Gender Differences, Hormones and Sex Chromosomes

Abstract

Background

Although the etiology of multiple sclerosis (MS) remains unknown, up to 70% of the risk is thought to be due to environmental factors. One largely understudied risk factor in MS is diet, including alcohol consumption. Because alcohol consumption is a modifiable lifestyle factor with immunological and neurological effects, it is important to understand its role in MS, especially given the high comorbidity between MS and alcohol use disorder. Our previous work demonstrated that low, chronic alcohol intake in a mouse model of MS – MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) – caused significantly greater remission of disease in male mice, but not in females.

Objectives

The effects of binge doses of alcohol on MS is not well understood. Our objective in this study was to assess how high doses of alcohol may affect the onset and progression of disease in two experimental murine models of CNS autoimmunity.

Methods

We utilized two models of EAE, MOG35-55 inducible model in C57BL/6 mice and 2D2 spontaneous EAE mouse model. In the C57BL/6 inducible EAE model, we administered a high dose of alcohol via oral gavage (3.5g/kg or control) three times per week for three weeks preceding induction of EAE and continued for 40 days post-induction. Clinical EAE scores were assessed daily starting on day 5 post-induction. In the spontaneous 2D2 model, adult 2D2 mice were fed a daily Lieber-DeCarli liquid diet containing alcohol (6% v/v or control), which provided a higher dosage of alcohol relative to the gavage experiment. Blood alcohol concentrations and daily caloric intake were assessed in the gavage and liquid diet model, respectively.

Results

In the C57BL/6 inducible MOG35-55 model, we observed that high dose of alcohol delayed the onset of disease in a sex-specific manner, with alcohol-consuming (AC) males developing delayed clinical EAE score peaks relative to isocaloric controls and compared to AC females. BAC measurements confirmed intoxication in this model, with a mean BAC of 324.7mg/dL. In the 2D2 model, AC males experienced a high death rate starting day 11 post-introduction of the alcohol diet, with a survival probability of AC males by day 16 of 0.375, prompting us to end the experiment. AC females had a higher survival probability of 0.75 by day 16.

Conclusions

The sensitivity of male mice to alcohol across different models of experimental autoimmunity is notable. Previously, we demonstrated that low levels of alcohol consumption in male mice with EAE was beneficial, so it was somewhat surprising that gavaging animals with a higher dose also provided a benefit. We hypothesize that after crossing a threshold in alcohol dosing, there would be a deleterious effect on disease onset and progression. This is supported by the high AC male death rate in the 2D2 mouse experiment. The current data warrant further study into how different doses of alcohol mediate beneficial or deleterious effects in EAE and inform future studies in patients with MS.

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Presenter Of 1 Presentation

Gender Differences, Hormones and Sex Chromosomes Poster Presentation

P1116 - Binge alcohol consumption in murine models of Multiple Sclerosis leads to sex-specific disease development.  (ID 1768)

Speakers
Presentation Number
P1116
Presentation Topic
Gender Differences, Hormones and Sex Chromosomes

Abstract

Background

Although the etiology of multiple sclerosis (MS) remains unknown, up to 70% of the risk is thought to be due to environmental factors. One largely understudied risk factor in MS is diet, including alcohol consumption. Because alcohol consumption is a modifiable lifestyle factor with immunological and neurological effects, it is important to understand its role in MS, especially given the high comorbidity between MS and alcohol use disorder. Our previous work demonstrated that low, chronic alcohol intake in a mouse model of MS – MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) – caused significantly greater remission of disease in male mice, but not in females.

Objectives

The effects of binge doses of alcohol on MS is not well understood. Our objective in this study was to assess how high doses of alcohol may affect the onset and progression of disease in two experimental murine models of CNS autoimmunity.

Methods

We utilized two models of EAE, MOG35-55 inducible model in C57BL/6 mice and 2D2 spontaneous EAE mouse model. In the C57BL/6 inducible EAE model, we administered a high dose of alcohol via oral gavage (3.5g/kg or control) three times per week for three weeks preceding induction of EAE and continued for 40 days post-induction. Clinical EAE scores were assessed daily starting on day 5 post-induction. In the spontaneous 2D2 model, adult 2D2 mice were fed a daily Lieber-DeCarli liquid diet containing alcohol (6% v/v or control), which provided a higher dosage of alcohol relative to the gavage experiment. Blood alcohol concentrations and daily caloric intake were assessed in the gavage and liquid diet model, respectively.

Results

In the C57BL/6 inducible MOG35-55 model, we observed that high dose of alcohol delayed the onset of disease in a sex-specific manner, with alcohol-consuming (AC) males developing delayed clinical EAE score peaks relative to isocaloric controls and compared to AC females. BAC measurements confirmed intoxication in this model, with a mean BAC of 324.7mg/dL. In the 2D2 model, AC males experienced a high death rate starting day 11 post-introduction of the alcohol diet, with a survival probability of AC males by day 16 of 0.375, prompting us to end the experiment. AC females had a higher survival probability of 0.75 by day 16.

Conclusions

The sensitivity of male mice to alcohol across different models of experimental autoimmunity is notable. Previously, we demonstrated that low levels of alcohol consumption in male mice with EAE was beneficial, so it was somewhat surprising that gavaging animals with a higher dose also provided a benefit. We hypothesize that after crossing a threshold in alcohol dosing, there would be a deleterious effect on disease onset and progression. This is supported by the high AC male death rate in the 2D2 mouse experiment. The current data warrant further study into how different doses of alcohol mediate beneficial or deleterious effects in EAE and inform future studies in patients with MS.

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