The Role of Trophic Factors and Other Drugs in the Treatment of Huntington's Disease in R6/2 Mouse Model

Huntington's disease (HD) is a rare, autosomal dominant, neurodegenerative disease, characterized by behavioral and cognitive deterioration, as well as a progressive loss in motor control. HD is thought to be caused by the expansion of trinucleotide, CAG, expansion at the N-terminus within exon 1 of the huntingtin gene. The huntingtin protein is considered to play a role in the cell survival and apoptosis pathways of neurons, including Akt kinase and JNK. We hypothesized that the treatment of the R6/2 transgenic mouse model with neurotrophic peptides, Colivelin and analogue dPEG-Colivelin, Sulforaphane, a compound that reduces oxidative stress, and Ceftriaxone, a GLT-1 upregulator, would attenuate motor behavioral abnormalities and neurodegeneration in HD R6/2 mouse model.Although we did not observe any behavioral motor improvement with Colivelin and dPEG-Colivelin, we did, in fact, find significant up-regulation of p-Akt in the ST of 40 mg/20g Colivelin treated R6/2 mice as compared to saline treated R6/2 mice. However, we did not observe any significant difference in the level of p-Akt in the PFC with Colivelin and dPEG-Colivelin treatments as compared to saline treated groups. Moreover, significant increase in p-JNK was observed in the ST and PFC of 40 mg/20g Colivelin treated R6/2 mice. Alternatively, we did not observe any behavioral improvements with Ceftriaxone or Sulforaphane.

Name thesis:degree_name

Master of Science in Pharmaceutical Science (MSP)

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

College of Pharmacy

Grantor dc:publisher

University of Toledo Health Science Campus

Year dc:date

2013

Author dc:creator

• Ciesler, Jessica

Contributors dc:contributor

• Sari, Youssef

• Pharmacology
• Pharmacy Sciences
• Neurosciences
• Huntington's Disease
• HD
• Colivelin
• dPEG-Colivelin
• R6/2
• Sulforaphane
• Ceftriaxone

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=mco1365173843

OAI identifier oai:identifier

oai:etd.ohiolink.edu:mco1365173843