Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA152125 | ENA |
REPOSITORIES: ENA
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Project description:Microarray comparison of transgenic mice overexpressing human alpha-synuclein under the PDGF beta promoter to wildtype littermates at 3 months and 9 months of age. RNA was extracted from substantia nigral cells that were isolated by laser capture microdissection.
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Project description:Shank3 is a core excitatory postsynaptic protein enriched in the striatum. We have previously generated and characterized Shank3-overexpressing transgenic mice, and found that these mice exhibited manic-like behavioral phenotypes. To understand molecular mechanisms underlying the behavioral changes, we performed transcriptome (RNA-sequencing) analysis of the striatal tissues from 12-week-old wild-type and Shank3 transgenic mice.
2017-08-17 | GSE97544 | GEO
Project description:Parkinsonâs disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression, or the A53T mutation, of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons. Here, we used two mouse lines overexpressing human A53T-SNCA around ages 6 and 18 months and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. High pressure liquid chromatography analysis of striatal neurotransmitter content demonstrated that dopamine (DA) levels correlated directly with the level of expression of SNCA, an observation also observed in SNCA deficient mice. In the striatum of aged A53TSNCA overexpressing mice, where DA levels were elevated, a paradoxical upregulation of dopamine receptors DRD1A and DRD2 was detected by immunoblots and autoradiography, findings compatible with the notion of abnormal vesicle release. Extensive transcriptome studies via microarrays and quantitative real-time RT-PCR validation of altered Homer1, Cb1, Atf2 and Pde7b transcript levels indicated a progressive reduction in the postsynaptic DA response. As functional consequences, long term depression was absent in corticostriatal slices from aged transgenic mice and an insidious decrease of spontaneous locomotor activity of these animals was found in open field tests. Taken together, the dysfunctional neurotransmission and decreased synaptic plasticity seen in the A53T-SNCA overexpressing mice reflects early functional changes within the basal ganglia resulting from synucleinopathy prior to frank neurodegeneration. Thus, preclinical stages of PD may be modeled in this mouse. Parkinsonâs disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression, or the A53T mutation, of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons. Here, we used two mouse lines overexpressing human A53T-SNCA around ages 6 and 18 months and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. High pressure liquid chromatography analysis of striatal neurotransmitter content demonstrated that dopamine (DA) levels correlated directly with the level of expression of SNCA, an observation also observed in SNCA deficient mice. In the striatum of aged A53TSNCA overexpressing mice, where DA levels were elevated, a paradoxical upregulation of dopamine receptors DRD1A and DRD2 was detected by immunoblots and autoradiography, findings compatible with the notion of abnormal vesicle release. Extensive transcriptome studies via microarrays and quantitative real-time RT-PCR validation of altered Homer1, Cb1, Atf2 and Pde7b transcript levels indicated a progressive reduction in the postsynaptic DA response. As functional consequences, long term depression was absent in corticostriatal slices from aged transgenic mice and an insidious decrease of spontaneous locomotor activity of these animals was found in open field tests. Taken together, the dysfunctional neurotransmission and decreased synaptic plasticity seen in the A53T-SNCA overexpressing mice reflects early functional changes within the basal ganglia resulting from synucleinopathy prior to frank neurodegeneration. Thus, preclinical stages of PD may be modeled in this mouse. Tissue was dissected from the brain of 6 months old (2 WT / 2 TgA / 2 TgB striata, 2 WT / 2 TgA / 2 TgB brainstems/midbrains, 2 WT / 2 TgA / 2 TgB cerebella) and of 18+ months old mice (4 WT / 2 TgA / 2 TgB striata, 6 WT / 4 TgA / 3 TgB brainstems/midbrains, 6 WT / 5 TgA / 4 TgB cerebella). Tissues from individual, particularly old mice up to 28 months age were included here to strengthen the definition of progression markers reflecting old age.
2010-05-27 | E-GEOD-20547 | biostudies-arrayexpress
Project description:Alpha-synuclein is an abundant protein implicated in synaptic function and plasticity, but the molecular mechanism of its action is not understood. Missense mutations and gene duplication/triplication events result in Parkinson's disease, a neurodegenerative disorder of old age with impaired movement and emotion control. Here, we systematically investigated the striatal as well as the cerebellar transcriptome profile of alpha-synuclein-deficient mice via a genome-wide microarray survey in order to gain hypothesis-free molecular insights into the physiological function of alpha-synuclein. A genotype-dependent, specific and strong downregulation of forkhead box P1 (Foxp1) transcript levels was observed in all brain regions from postnatal age until old age and could be validated by qPCR. In view of the co-localization and heterodimer formation of FOXP1 with FOXP2, a transcription factor with a well established role for vocalization, and the reported regulation of both alpha-synuclein and FOXP2 expression during avian song learning, we performed a detailed assessment of mouse movements and vocalizations in the postnatal period. While there was no difference in isolation-induced behavioral activity in these animals, the alpha-synuclein-deficient mice exhibited an increased production of isolation-induced ultrasonic vocalizations (USVs). This phenotype might also reflect the reduced expression of the anxiety-related GABA-A receptor subunit gamma 2 (Gabrg2) we observed. Taken together, we identified an early behavioral consequence of alpha-synuclein deficiency and accompanying molecular changes, which supports the notion that the neural connectivity of sound or emotion control systems is affected. Factorial design comparing SNCA knock-out mice with wild type littermates in two different tissues (striatum, cerebellum) at two different timepoints (6 and 21 month)
2010-07-21 | E-GEOD-19534 | biostudies-arrayexpress
Project description:Synucleinopathies are age-dependent neurodegenerative diseases characterized by alpha-synuclein accumulation with distinct vulnerabilities across brain regions. Understanding early disease stages is essential to uncover initial molecular changes that might enable earlier diagnosis and causal therapy. Here, we profiled longitudinal and brain region-resolved gene expression changes in a rat model of synucleinopathies overexpressing human SNCA. Transcriptomic analyses on gene and transcript level of striatal, frontocortical, and cerebellar tissue in 5- and 12-month-old transgenic (BAC SNCA) and wild type rats revealed that SNCA overexpression leads to age-dependent transcriptomic changes that largely occur region-specific. In frontal cortex, dysregulation of myelination-associated genes agreed with Parkinson patient data as shown before. In addition, BAC SNCA rats displayed more gene expression changes at younger age, with a common and distinctive dysregulation pattern across all three examined brain regions. We also identified a cross-regional set of differential genes with similar perturbation patterns that were affected by SNCA overload. This set was also partially reflected in the gut transcriptome of the same rat model, suggesting a systemic impact of SNCA overload. Taken together, our findings highlight both brain region-specific vulnerabilities and global molecular perturbations associated with alpha-synuclein biology and provide insights into early transcriptomic changes in synucleinopathies.
2025-04-01 | GSE281984 | GEO
Project description:In order to investigate the effect of Alpha-Ketoglutarate (AKG) on p-α-synuclein in substantia nigra of Parkinson's disease (PD) model mice (C57BL/6), we profiled substantia nigra from wild-type (WT), AAV-α-synuclein (α-Syn), AKG and α-Syn-AKG in male mice by RNA sequencing (RNA-seq).
2022-10-02 | GSE214446 | GEO
Project description:Alpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinson’s disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD. To gain a better understanding of the consequences of excessive SNCA expression on basal ganglia function, we performed transcriptome analysis of striatal tissue from male Thy1-aSyn-mice and wt littermates. The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis. The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis.
2012-02-11 | GSE35723 | GEO