Aging African Green Monkeys manifest transcriptional, pathological, and cognitive hallmarks of human Alzheimer’s disease
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE108282
PROVIDER: PRJNA423026 | ENA |
REPOSITORIES: ENA
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Project description:While many preclinical models of Alzheimer’s disease (AD) have been reported, none fully recapitulate the disease. In an effort to identify an appropriate preclinical disease model, we characterized age-related changes in two higher order species, the African Green Monkey (AGM) and the rhesus macaque. Gene expression profiles in the dorsolateral prefrontal cortex and the visual cortex showed age-related changes in AGMs that are strikingly reminiscent of AD, whereas aged rhesus were most similar to healthy elderly humans. Biochemically, age-related changes in AGM cerebrospinal fluid levels of tau, phospho-tau and amyloid beta were consistent with AD. Histologically, aged AGMs displayed pathological hallmarks of the disease, plaques, and two AGMs showed evidence of neurofibrillary tangle-like structures. We hypothesized and confirmed that AGMs have age-related cognitive deficits via a prefrontal cortex-dependent cognition test, and that symptomatic treatments which improve cognition in AD patients show efficacy in AGMs. These data suggest that the AGM could represent a novel and improved translational model to assist in the development of therapeutics for AD.
2018-02-01 | GSE108282 | GEO
Project description:In contrast to SIVagm, which does not cause disease in its natural simian host, HIV-1 expresses the accessory protein Vpu and encodes a Nef protein that fails to suppress T cell activation via down-modulation of CD3. Although both, Vpu and Nef have been implicated as pathogenicity determinants, their relevance for viral replication and disease progression in vivo has remained unclear. Here, we analyzed gene expression in African green monkeys infected with SIVagm chimeras differing in their expression of nef and/or vpu. We used microarrays to analyze global gene expression of African green monkeys in response to infection with SIVagm and found that the viral accessory nef and vpu genes co-determine the induction of distinct gene sets.
2018-03-02 | GSE103072 | GEO
Project description:Investigation of whole genome gene expression level changes in African Green Monkeys treated with antimiR-33a/b, compared to the animal treated with vehicle The treatment of the monkeys is further described in Rottiers V, Obad S, McGarrah R, Black JC, Lindholm M, Goody R, Lawrence M, Whetstine JR, Gerszten RE, Kauppinen S, NM-CM-$M-CM-$r AM. (2013). Pharmacological inhibition of a microRNA family in non-human primates by a seed-targeting 8-mer antimiR oligonucleotide. Accepted for publication at Science Translational Medicine. MicroRNAs (miRNAs) regulate many aspects of human biology. They target mRNAs for translational repression or degradation through base-pairing with 3M-bM-^@M-^Y UTRs, primarily via seed sequences (nucleotides 2-8 in the mature miRNA sequence). A number of individual miRNAs and miRNA families share seed sequences and targets, but differ in the sequences outside of the seed. miRNAs have been implicated in the etiology of a wide variety of human diseases and therefore represent promising therapeutic targets. However, potential redundancy and compensatory action of different miRNAs sharing the same seed sequence, and the challenge of simultaneously targeting miRNAs that differ significantly in non-seed sequences complicates therapeutic targeting approaches. We recently demonstrated effective inhibition of entire miRNA families using seed-targeting 8-mer locked nucleic acid (LNA)-modified antimiRs in short-term experiments in mammalian cells and in mice. However, the long-term efficacy and safety of this approach in higher organisms, such as humans and non-human primates, has not been determined. Here, we show that pharmacological inhibition of the miR-33 family, key regulators of cholesterol/lipid homeostasis, by a subcutaneously delivered 8-mer LNA-modified antimiR in obese and insulin-resistant non-human primates results in de-repression of miR-33 targets, such as ABCA1, increases circulating high-density lipoprotein-cholesterol (HDL-C), and is well tolerated over 108 days of treatment. These findings demonstrate the efficacy and safety of an 8-mer LNA-antimiR against a miRNA family in a non-human primate metabolic disease model, suggesting that this could be a feasible approach for therapeutic targeting of miRNA families sharing the same seed sequence in human diseases. Expression analysis study in obese Non Human Primates (African Green Monkeys). Five animals treated with antimiR-33a/b were compared to five animals treated with vehicle.
2013-08-23 | E-GEOD-50116 | biostudies-arrayexpress
Project description:Detailed knowledge about dynamics of SARS-CoV-2 infection in vivo is important for unraveling the viral and host response factors that contribute to COVID-19 pathogenesis. The unknown dose and exposure timing in human infections makes the needed well-controlled time course studies impossible and thus animal models of disease are essential to fill in the gaps in our understanding of disease progression. Old-World nonhuman primate species recapitulate mild COVID-19 cases, thereby serving as important models for studying disease pathogenesis. In this study, we compare African green monkeys (AGM; Chlorocebus sabaeus) inoculated with SARS-CoV-2 to AGM inoculated with a gamma-irradiated form of the virus to study the dynamics of virus replication throughout the respiratory tract and other target tissues. RNA sequencing of single cells from the lungs and mediastinal lymph nodes allowed a high-resolution, simultaneous analysis of virus replication and the host response in these tissues over time. Viral replication was mainly localized to the lower respiratory tract, especially the pneumocyte population. However, even in the absence of active replication, viral genomic RNA is was highly stable, especially in the upper respiratory tract. Macrophages play a vital and dynamic role in initiating a pro-inflammatory state in the lungs, while also interacting with infected pneumocytes. Together, our dataset provides a detailed view of changes in host and virus replication dynamics over the course of a mild COVID-19 infection and serves as a valuable resource to identify new therapeutic targets.
2021-01-14 | GSE156755 | GEO
Project description:SARS-CoV-2 infection dynamics in lungs of African green monkeys
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Project description:Type 2 diabetes mellitus (TM) is a severely metabolic disorder that affects above 10% worldwide population. Obesity is a major cause of insulin resistance and contributes to the development of TM. Liver is an essential metabolic organ that plays crucial roles in the pathogenesis of obesity and diabetes. However, the underlying mechanisms of liver in the transition of obesity to diabetes are not fully understood. Nonhuman primate (NHP) rhesus monkey is an appropriate animal for research of human diseases. Here, we first screened and selected three individual spontaneous and diabetic rhesus monkeys. Interestingly, the diabetic monkeys were obese with high BMI at beginning, but gradually lost their body weight during one-year observation. Furthermore, we performed a SILAC-based quantitative proteomics to identify proteins and signaling pathways with altered expression in the liver of obese and diabetic monkeys. Totally, 3509 proteins were identified and quantified, and of which 185 proteins displayed altered expression level. GO analysis revealed that the expression of proteins involved in fatty acids β-oxidation and galactose metabolism was increased in obese monkeys; while proteins involved in oxidative phosphorylation (OXPHOS) and branched chain amino acid (BCAA) degradation was upregulated in diabetic monkeys. In addition, we observed a mild impaired mitophagy and apoptosis in the liver of diabetic monkeys, suggesting a dysfunction of mitochondria and liver injury in the late onset of diabetics. Taken together, our liver proteomics may reveal a distinct metabolic transition from fatty acids β-oxidation in obese monkey to BCAA degradation in diabetic monkeys.
2019-08-26 | PXD008825 | Pride
Project description:Howler monkeys feces bacterial isolates
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Project description:Investigation of whole genome gene expression level changes in African Green Monkeys treated with antimiR-33a/b, compared to the animal treated with vehicle The treatment of the monkeys is further described in Rottiers V, Obad S, McGarrah R, Black JC, Lindholm M, Goody R, Lawrence M, Whetstine JR, Gerszten RE, Kauppinen S, Näär AM. (2013). Pharmacological inhibition of a microRNA family in non-human primates by a seed-targeting 8-mer antimiR oligonucleotide. Accepted for publication at Science Translational Medicine. MicroRNAs (miRNAs) regulate many aspects of human biology. They target mRNAs for translational repression or degradation through base-pairing with 3’ UTRs, primarily via seed sequences (nucleotides 2-8 in the mature miRNA sequence). A number of individual miRNAs and miRNA families share seed sequences and targets, but differ in the sequences outside of the seed. miRNAs have been implicated in the etiology of a wide variety of human diseases and therefore represent promising therapeutic targets. However, potential redundancy and compensatory action of different miRNAs sharing the same seed sequence, and the challenge of simultaneously targeting miRNAs that differ significantly in non-seed sequences complicates therapeutic targeting approaches. We recently demonstrated effective inhibition of entire miRNA families using seed-targeting 8-mer locked nucleic acid (LNA)-modified antimiRs in short-term experiments in mammalian cells and in mice. However, the long-term efficacy and safety of this approach in higher organisms, such as humans and non-human primates, has not been determined. Here, we show that pharmacological inhibition of the miR-33 family, key regulators of cholesterol/lipid homeostasis, by a subcutaneously delivered 8-mer LNA-modified antimiR in obese and insulin-resistant non-human primates results in de-repression of miR-33 targets, such as ABCA1, increases circulating high-density lipoprotein-cholesterol (HDL-C), and is well tolerated over 108 days of treatment. These findings demonstrate the efficacy and safety of an 8-mer LNA-antimiR against a miRNA family in a non-human primate metabolic disease model, suggesting that this could be a feasible approach for therapeutic targeting of miRNA families sharing the same seed sequence in human diseases.
2013-08-23 | GSE50116 | GEO
Project description:Ovariectomized monkeys were treated with placebo, estrogen or estrogen plus progesterone for one month. The brain was perfused with RNA Later plus 20% sucrose. Sections through the dorsal raphe nucleus were immunostained for TPH and then TPH positive neurons were laser captured. The RNA was extracted and hybridized to the Rhesus Affymetrix chip. Each chip represents one monkey. N=2 monkeys per treatment.
2010-04-08 | E-GEOD-16169 | biostudies-arrayexpress
Project description:Female C57BL/6J mice hemizygous for the 5XFAD transgene (MMRRC Stock No #34848-JAX) were bred to males from BXD strains, which do not carry the 5XFAD transgene. The resulting F1 progeny were monitored throughout their lifespan to evaluate the effect of genetic background on cognitive and pathological traits. All of the mice were fear conditioned and sacrificed within 30 minutes of testing. On the sample records, the characteristics: age field provides the age at which fear conditioning, sacrifice, and tissue collection occurred. Samples here come from various AD-BXD lines and their non-transgenic (Ntg) littermate counterparts at either 6 or 14 months of age.
2018-12-14 | GSE101144 | GEO