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Evidence of age‐related neuronal aberrations and dysfunction of sensory neurons in a polyglutamine model of Huntington's disease
Author(s) -
Vayndorf Elena,
Driscoll Monica,
Taylor Barbara
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.710.5
Subject(s) - huntingtin , huntington's disease , trinucleotide repeat expansion , biology , neuroscience , sensory system , huntingtin protein , neurodegeneration , amyotrophic lateral sclerosis , microbiology and biotechnology , disease , gene , genetics , pathology , medicine , allele
Huntington's disease is a neurodegenerative disorder that impairs motor movements and cognitive ability. It is caused by expansion of the CAG trinucleotide repeat within the first exon of the huntingtin ( HTT ) gene. The resulting polyglutamine (polyQ) chain gives rise to a mutated huntingtin protein, which is associated with aggregate formation, neuronal dystrophy and severe dysfunction. C. elegans is a genetically tractable model whose intact nervous system possesses major hallmarks of mammalian neurological function. Our model of Huntington's disease expresses the toxic (Q128) and non‐toxic (Q19) forms of the polyglutamine chain in the mechanosensory neurons. We hypothesized that, compared to animals expressing non‐toxic huntingtin, animals expressing the toxic protein would exhibit significant morphological aberrations of mechanosensory neurons and the degree of aberrancy would correlate with age‐related reduced functionality and short‐term associative memory. Sensory neurons were imaged throughout the lifespan using fluorescent microscopy and standard nematode culturing techniques. Mechanosensory assays were performed by provoking animal response to gentle touch. Short‐term memory assays were conducted using an associative chemotaxis assay. Results indicate that expression of toxic huntingtin correlates with neuronal aberrations and defects in mechanosensory sensation with age.