Helper-dependent CAV-2 vector-mediated LRRK2G2019S expression in the M. murinus brain induces Parkinson's disease-like histological lesions and motor symptoms
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PROVIDER: PRJNA400185 | ENA |
REPOSITORIES: ENA
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Project description:Parkinson disease (PD) is a neurodegenerative disease primarily associated with impaired movement affecting elderly people. To improve the understanding of the pathogenesis and to develop new therapies, we have developed a non-human primate model of PD using the lemurian Microcebus murinus (Mim). In this study, we tested the potential of canine adenovirus type 2 (CAV-2) as vector for gene transfer in the Mim brain by analyzing the gene expression changes in three regions involved in motor control: striatum, frontal cortex and midbrain. The CAV-2 viruses were injected in the right striatum of young adult females, 2 years old. CAV-2 vectors preferentially transduce neurons in the primate brain and were carried by axonal transport to afferent structures in both hemispheres. The gene expression changes were analyzed at 2 critical times after infection by CAV-2: an acute time effect at 24h and a delayed time effect at 28 days post infection. In addition, the gene expression was compared in the ipsilateral side versus the contralateral side, and with a non-infected brain samples using human Affymetrix microarrays. The transcriptomic data were analyzed by Significance Analysis of Microarrays (SAM) to identify genes differentially expressed when comparing brain samples in the 3 conditions. The data were also analyzed by ANOVA one way and by Principal Component Analysis (PCA). The results have shown that the transduction of CAV2 in neurons induced specific changes. These changes differed during the immediate and the long-term-point. Gene expression changes were detected in transcriptional regulation, in synaptic transmission, in cellular trafficking and in immune response. More precisely, in the short term, CAV2 activated genes involved in a non-specific innate immune response. In the long term, CAV2 induced an adaptive tolerant immune response. Gene expression changes in the striatum of Microcebus murinus induced by Canine adenovirus type 2 (CAV-2)
2018-03-01 | GSE102640 | GEO
Project description:Parkinson disease (PD) is a neurodegenerative disease primarily associated with impaired movement affecting elderly people. To improve the understanding of the pathogenesis and to develop new therapies, we have developed a non-human primate model of PD using the lemurian Microcebus murinus (Mim). In this study, we tested the potential of canine adenovirus type 2 (CAV-2) as vector for gene transfer in the Mim brain by analyzing the gene expression changes in three regions involved in motor control: striatum, frontal cortex and midbrain. The CAV-2 viruses were injected in the right striatum of young adult females, 2 years old. CAV-2 vectors preferentially transduce neurons in the primate brain and were carried by axonal transport to afferent structures in both hemispheres. The gene expression changes were analyzed at 2 critical times after infection by CAV-2: an acute time effect at 24h and a delayed time effect at 28 days post infection. In addition, the gene expression was compared in the ipsilateral side versus the contralateral side, and with a non-infected brain samples using human Affymetrix microarrays. The transcriptomic data were analyzed by Significance Analysis of Microarrays (SAM) to identify genes differentially expressed when comparing brain samples in the 3 conditions. The data were also analyzed by ANOVA one way and by Principal Component Analysis (PCA). The results have shown that the transduction of CAV2 in neurons induced specific changes. These changes differed during the immediate and the long-term-point. Gene expression changes were detected in transcriptional regulation, in synaptic transmission, in cellular trafficking and in immune response. More precisely, in the short term, CAV2 activated genes involved in a non-specific innate immune response. In the long term, CAV2 induced an adaptive tolerant immune response. Gene expression changes in the midbrain of Microcebus murinus induced by Canine adenovirus type 2 (CAV-2)
2018-03-01 | GSE102709 | GEO
Project description:Parkinson disease (PD) is a neurodegenerative disease primarily associated with impaired movement affecting elderly people. To improve the understanding of the pathogenesis and to develop new therapies, we have developed a non-human primate model of PD using the lemurian Microcebus murinus (Mim). In this study, we tested the potential of canine adenovirus type 2 (CAV-2) as vector for gene transfer in the Mim brain by analyzing the gene expression changes in three regions involved in motor control: striatum, frontal cortex and midbrain. The CAV-2 viruses were injected in the right striatum of young adult females, 2 years old. CAV-2 vectors preferentially transduce neurons in the primate brain and were carried by axonal transport to afferent structures in both hemispheres. The gene expression changes were analyzed at 2 critical times after infection by CAV-2: an acute time effect at 24h and a delayed time effect at 28 days post infection. In addition, the gene expression was compared in the ipsilateral side versus the contralateral side, and with a non-infected brain samples using human Affymetrix microarrays. The transcriptomic data were analyzed by Significance Analysis of Microarrays (SAM) to identify genes differentially expressed when comparing brain samples in the 3 conditions. The data were also analyzed by ANOVA one way and by Principal Component Analysis (PCA). The results have shown that the transduction of CAV2 in neurons induced specific changes. These changes differed during the immediate and the long-term-point. Gene expression changes were detected in transcriptional regulation, in synaptic transmission, in cellular trafficking and in immune response. More precisely, in the short term, CAV2 activated genes involved in a non-specific innate immune response. In the long term, CAV2 induced an adaptive tolerant immune response. Gene expression changes in the frontal cortex of Microcebus murinus induced by Canine adenovirus type 2 (CAV-2)
2018-03-01 | GSE102708 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-03-01 | GSE103099 | GEO
Project description:Gene expression changes in the striatum of Microcebus murinus induced by Canine adenovirus type 2 (CAV-2)
| PRJNA398267 | ENA
Project description:Gene expression changes in the midbrain of Microcebus murinus induced by Canine adenovirus type 2 (CAV-2)
| PRJNA398483 | ENA
Project description:Gene expression changes in the frontal cortex of Microcebus murinus induced by Canine adenovirus type 2 (CAV-2)
| PRJNA398482 | ENA