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Rattus norvegicus
36 Downloadable Samples
Illumina HiSeq 2500
Description
We examined effects of early life stress (ELS) and environmental enrichment (EE) during development on BACHD rat striatal gene expression using RNA sequencing Overall design: We used a 2×3 factorial design with two genotypes (wildtype, WT; transgene, TG) and three environmental conditions (standard environment, SE; enriched environment, EE; early life stress, ELS) to assess effects of environmental enrichment and early life stress on striatal gene expression of 2-month-old WT and BACHD rats
Publication Title
Environment-dependent striatal gene expression in the BACHD rat model for Huntington disease.
Sample Metadata Fields
No sample metadata fields
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GSE1918- Rattus norvegicus
- 14 Downloadable Samples
Affymetrix Rat Expression 230A Array (rae230a)
Description
4 Treatment groups:
Publication Title
Dysregulation of gene expression in primary neuron models of Huntington's disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Primary neuron model of Huntington's Disease. 2 treatment groups: A) Infected 4 weeks prior with TRE-Htt-N853-18Q-expressing recombinant lentivirus, B) Infected 4 weeks prior with TRE-Htt-N853-82Q-expressing recombinant lentivirus
Publication Title
Dysregulation of gene expression in primary neuron models of Huntington's disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Ion Torrent Proton
Description
The neurobiological functions of a number of kinases expressed in the brain are unknown. Here, we report new findings on DCLK3 (Doublecortin-like kinase 3) which is preferentially expressed in neurons in the striatum and dentate gyrus. Its function has never been investigated. DCLK3 expression is markedly reduced in Huntington''s disease. Recent data obtained in studies related to cancer suggest DCLK3 could have anti-apoptotic effect. Thus, we hypothesized that early loss of DCLK3 in Huntington''s disease may render striatal neurons more susceptible to mutant huntingtin (mHtt). We discovered that DCLK3 silencing in the striatum of mice exacerbated the toxicity of an N-terminal fragment of mHtt. Conversely, overexpression of DCLK3 reduced neurodegeneration produced by mHtt. DCLK3 also produced beneficial effects on motor symptoms in a knock-in mouse model of Huntington''s disease. Using different mutants of DCLK3, we found that the kinase activity of the protein plays a key role in neuroprotection. To investigate the potential mechanisms underlying DCLK3 effects, we studied the transcriptional changes produced by the kinase domain in human striatal neurons in culture. Results show that DCLK3 regulates in a kinase-dependent manner the expression of many genes involved in transcription regulation and nucleosome/chromatin remodeling. Consistent with this, histological evaluation showed DCLK3 is present in the nucleus of striatal neurons and, protein-protein interaction experiments suggested that the kinase domain interacts with zinc finger proteins, including TADA3, a core component of SAGA complex. Our novel findings suggest that the presence of DCLK3 in striatal neurons may play a key role in transcription regulation and chromatin remodeling in these brain cells, and show that reduced expression of the kinase in Huntington's disease could render the striatum highly vulnerable to neurodegeneration. Examination of DCLK3 as neuroprotector against mutant huntingtin in vivo and in vitro models. Overall design: Examination of DCLK3 as neuroprotector against mutant huntingtin in vitro experiments.
Publication Title
The striatal kinase DCLK3 produces neuroprotection against mutant huntingtin.
Sample Metadata Fields
Specimen part, Cell line, Subject
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