Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1047189 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27042868_1.fastq.gz | Fastqsanger.gz | |||
| SRR27042868_2.fastq.gz | Fastqsanger.gz | |||
| SRR27042869_1.fastq.gz | Fastqsanger.gz | |||
| SRR27042869_2.fastq.gz | Fastqsanger.gz | |||
| SRR27042870_1.fastq.gz | Fastqsanger.gz |
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Project description:<p><strong>BACKGROUND:</strong> Ochratoxin A (OTA) have made it a serious hazard to food safety worldwide that poses a serious health risk to humans. Our previous research showed that Walnut green husk polysaccharides (WGP) can effectively alleviate intestinal inflammation and intestinal microbiota disturbances caused by OTA. The present study further explored whether WGP can prevents OTA-induced cognitive impairments and elucidate its neuroprotective mechanism. Here, we established fecal microbiota transplantation, Lactobacillus johnsonii (L.john) and Akkermansia muciniphila (AKK) colonization, L.john and AKK-derived extracellular vesicles (EVs), as well as 5-HT and short-chain fatty acid (SCFA) supplementation tests to evaluate the role of the intestinal microbiota and its metabolites in WGP in alleviating OTA-induced cognitive impairment. </p><p><strong>RESULTS:</strong> OTA exposure induced cognitive impairments and inhibition of hippocampal neurogenesis, which was reversed by WGP supplementation. Meanwhile, WGP supplementation significantly reversed OTA-induced gut dysbacteriosis and low abundance of L.john and AKK, high proinflammation factor levels and low neurotransmitter levels in serum, intestine and hippocampus, as well as low SCFA levels in fecal. Antibiotic cocktail treatment eliminates the neuroprotective effect of WGP on OTA-treated mice. In addition, transplantation of the OTA-gut microbiota into normal mice causing similar results to OTA treatment, and these changes were alleviated with the transplantation of OTA+WGP-gut microbiota. Furthermore, colonization with L.john and AKK markedly reversed OTA-induced cognitive impairments and inhibition of hippocampal neurogenesis, as well as increased 5-HT and SCFA levels. EVs derived from L.john and AKK exhibit consistent performance with colonized L.john and AKK, and also have superior abilities in alleviating OTA-induced cognitive impairment and inhibiting hippocampal neurogenesis. Moreover, as a key regulatory factor of microbiota-gut-brain axis, 5-HT and SCFA supplementation significantly alleviated OTA-induced cognitive impairment and inhibition of hippocampal neurogenesis. </p><p><strong>CONCLUSIONS:</strong> Taken together, this work provides new evidence for microbiota-gut-brain axis involved in the neuroprotective effects of WGP on OTA-induced cognitive dysfunction. L.john, AKK and its derived EVs mediate the ameliorative effects of WGP on OTA-induced cognitive impairment. A feasible mechanism is that WGP increased the content of L.john, AKK and its derived EVs, which improve 5-HT and SCFA production in colon to ameliorate cognitive impairment and enhance hippocampal neurogenesis.</p>
2024-10-10 | MTBLS10673 | MetaboLights
Project description:- Background: Obesity in mid-adulthood has been suggested to promote brain aging and is associated with progressive cognitive impairment later in life. However, the structural and functional alterations that underlie obesity-related cognitive dysfunction are still poorly understood, partly owing to the lack of translational models replicating age- and obesity-related brain pathology. - Methods: The effect of age and high-fat diet (HFD)-induced obesity was investigated in adult Ldlr-/-.Leiden mice, an established translational model for obesity and its comorbidities. During mid-adulthood, from three to eight months of age, brain structure and function (hippocampal volume, cortical thickness, white matter integrity, cerebral blood flow (CBF), resting-state functional connectivity) were monitored with brain magnetic resonance imaging, and cognitive function was evaluated using cognitive tests. Brain pathology was further examined with histopathological and gene expression analyses. - Results: Ldlr-/-.Leiden mice showed age-related decreases in cortical thickness, CBF, brain connectivity, and neurogenesis along with the development of neuroinflammation and (short-term) memory impairments. On HFD feeding, Ldlr-/-.Leiden mice exhibited similar features, but memory deficits started at a younger age than in chow-fed mice. HFD-fed mice additionally showed a rise in CBF with concomitant decline in fractional anisotropy in white matter tracts. Analyses of hippocampal gene expression further revealed an age-related suppression of processes related to metabolic and neuronal function while HFD feeding strongly activated neuroinflammatory pathways. - Conclusions: Ldlr-/-.Leiden mice show similar critical age-related changes in brain structure and function as observed in humans. In this mouse model, HFD feeding particularly trigger disturbances in brain blood perfusion and white matter tract integrity, which may underlie an accelerated cognitive decline in obesity.
2025-04-30 | GSE294054 | GEO
Project description:Topoisomerase 3b (Top3b) is the only dual-activity topoisomerase in animals that can change topology for both DNA and RNA, and facilitate transcription on DNA and translation on mRNAs. Top3b mutation has been linked to schizophrenia, autism, epilepsy, and cognitive impairment. However, whether and how Top3b mutations are causal to these disorders remain unclear. Here we show that Top3b knockout mice exhibit behavioral phenotypes related to psychiatric disorders and cognitive impairment, including increased anxiety and fear, abnormal social interactions, impaired context discrimination, and defective spatial learning and memory. In addition, these mice display deficits in adult hippocampal neurogenesis and synaptic plasticity. Notably, the brains of the mutant mice exhibit impaired global neuronal activity-dependent transcription in response to fear conditioning stress, and the affected genes include many that are critical for neuronal functions and mental health. Our data suggest that Top3b is essential for normal brain function in multiple domains, and defective neuronal activity-dependent transcription may be a mechanism by which Top3b deletion causes cognitive impairment and psychiatric disorders.
2020-05-22 | GSE145730 | GEO
Project description:Obesity is a growing global concern in adults and youth along with a parallel rise in associated complications, including cognitive impairment. Obesity induces brain inflammation and activates microglia, which contribute to cognitive impairment by aberrantly phagocytosing synaptic spines. Local and systemic signals, such as inflammatory cytokines and metabolites likely participate in obesity-induced microglial activation. However, the precise mechanisms mediating microglial activation during obesity remain incompletely understood. Herein, we leveraged our mouse model of high-fat diet (HFD)-induced obesity, which mirrors human obesity, and develops hippocampal-dependent cognitive impairment. We assessed hippocampal microglial activation by morphological and single-cell transcriptomic analysis to evaluate this heterogeneous, functionally diverse, and dynamic class of cells over time after 1 and 3 months of HFD. HFD altered cell-to-cell communication, particularly immune modulation and cellular adhesion signaling, and induced a differential gene expression signature of protein processing in the endoplasmic reticulum in a time-dependent manner.
2023-02-17 | GSE217464 | GEO
Project description:Objective Obesity is a multidimensional condition that is treatable by the restoration of a lean phenotype; however, some obesity-related outcomes may persist after weight normalization. Among the organs of the human body, the brain possesses a relatively low regenerative capacity and could retain perturbations established as a result of developmental obesity. Calorie restriction (CR) or a restricted ketogenic diet (KD) are successfully used as weight loss approaches, but their impact on obesity-related effects in the brain have not been previously evaluated. Methods We performed a series of experiments in a rat model of developmental obesity induced by a 12-week cafeteria diet, followed by CR to implement weight loss. First, we assessed the impact of obesity on neurogenesis (BrdU incorporation into the hippocampus), cognitive function (water maze), and concomitant changes in hippocampal protein expression (GC/MS-MS, western blot). Next, we repeated these experiments in a rat model of weight loss induced by CR. We also measured mitochondrial enzyme activity in rats after weight loss during the fed or fasting state. By using a modified version of the water maze we evaluated cognitive abilities in rats subjected to weight loss by CR or a restricted KD. Results In this study, obesity affected metabolic processes, upregulated hippocampal NF-κB, and induced proteomic differences which were associated with impaired cognition and neurogenesis. Weight loss improved neurogenesis and enhanced cognition. While the expression pattern of some proteins persisted after weight loss, most of the changes appeared de novo revealing metabolic adjustment by overactivation of citrate synthase and downregulation of ATP synthase. As a consequence of fasting, the activity of these enzymes indicated hippocampal adaptation to negative energy balance during the weight loss phase of CR. Moreover, the effects on cognitive abilities measured after weight loss were negatively correlated with the obesity level and were alleviated by KD, which improved cognition when used as a weight loss approach. Conclusions The study shows that cognition and mitochondrial metabolism in the hippocampus are affected by CR- or KD-induced weight loss.
2021-07-01 | PXD023070 | Pride
Project description:Tissue stem cell senescence leads to stem cell exhaustion, which results in tissue homeostasis imbalance and a decline in regeneration capacity. However, whether neural stem cells (NSCs) senescence occurs and causes neurogenesis reduction during aging is unknown. In this study, mice at different ages were used to detect age-related hippocampal NSCs (H-NSCs) senescence, as well as the function and mechanism of embryonic stem cells derived small extracellular vesicles (ESC-sEVs) in rejuvenating H-NSCs senescence. We found a progressive cognitive impairment, as well as age-related H-NSCs senescence, in mice. ESC-sEVs treatment significantly alleviated H-NSCs senescence, recovered compromised self-renewal and neurogenesis capacities, and reversed cognitive impairment. Transcriptome analysis revealed that Myelin transcription factor 1 (MYT1) is downregulated in senescent H-NSCs but upregulated by ESC-sEV treatment. In addition, knockdown of MYT1 in young H-NSCs accelerated age-related phenotypes and impaired proliferation and differentiation capacities. Mechanistically, ESC-sEVs rejuvenated senescent H-NSCs partly by transferring SMAD4 and SMAD5 to activate MYT1, which downregulated Egln3, followed by activation of HIF2α, NAMPT, and Sirt1 successively. Taken together, our results indicated that H-NSCs senescence caused cellular exhaustion, neurogenesis reduction and cognitive impairment during aging, which can be reversed by ESC-sEVs. Thus, ESC-sEVs may be promising therapeutic candidates for age-related diseases.
2023-09-09 | GSE158000 | GEO
Project description:Hippocampal pathways in cognitive impairment
| PRJNA96943 | ENA
Project description:Failure of neural stem/progenitor cell (NSPC) activity and subsequently neurogenesis during brain development has been linked to cognitive impairment and intellectual disability. However, it remains unclear if changes in metabolism, recently discovered as a key regulator of somatic stem cell activity, contribute to altered neurogenesis and cognitive deficits in humans. To investigate a link between NSPC-associated lipid metabolism and brain development, we generated mice and human embryonic stem cells (hESCs) mimicking a variant in fatty acid synthase (FASN; R1819W), a metabolic regulator of rodent NSPC activity recently identified in humans with intellectual disability. Mice homozygous for the FASN R1812W variant have impaired hippocampal NSPC activity associated with cognitive impairment due to presumed toxic accumulation of lipids in NSPCs and subsequent lipogenic ER stress. Human NSPCs homozygous for the FASN R1819W variant show reduced rates of proliferation in embryonic 2D cultures and 3D forebrain regionalized organoids, revealing that the functional significance of lipid metabolism for neurogenic proliferation of progenitors is conserved between rodents and humans. By taking a disease modeling approach, using mouse and human tissue genome engineering, our data provide genetic evidence for a link between altered lipid metabolism, NSPC activity and brain function.
2020-03-18 | GSE115851 | GEO
Project description:Our findings suggested that exposure to CeCl3 led to hippocampal lesions, apoptosis, oxidative stress and impairment of spatial recognition memory. Furthermore, microarray data showed marked alterations in the expression of 154 genes involved in learning and memory, immunity and inflammation, signal transduction, apoptosis and response to stress in the 2 mg/kg CeCl3 exposed hippocampi. Cerium is widely used in many aspects of modern society, including agriculture, industry and medicine. It has been demonstrated to enter the ecological environment, is then transferred to humans through food chains, and causes toxic actions in several organs including the brain of animals. However, the neurotoxic molecular mechanisms are not clearly understood. In this study, mice were exposed to 0.5, 1, and 2 mg/kg BW cerium chloride (CeCl3) for 90 consecutive days, and their learning and memory ability as well as hippocampal gene expression profile were investigated. Our findings suggested that exposure to CeCl3 led to hippocampal lesions, apoptosis, oxidative stress and impairment of spatial recognition memory. Furthermore, microarray data showed marked alterations in the expression of 154 genes involved in learning and memory, immunity and inflammation, signal transduction, apoptosis and response to stress in the 2 mg/kg CeCl3 exposed hippocampi. Specifically, the significant up-regulation of Axud1, Cdc37, and Ube2v1 caused severe apoptosis, and great suppression of Adcy8, Fos, and Slc5a7 expression led to impairment of mouse cognitive ability. Therefore, Axud1, Cdc37, Ube2v1, Adcy8, Fos, and Slc5a7 may be potential biomarkers of hippocampal toxicity caused by CeCl3 exposure. In this study, mice were exposed to 0.5, 1, and 2 mg/kg BW cerium chloride (CeCl3) for 90 consecutive days, and their learning and memory ability as well as hippocampal gene expression profile were investigated.
2013-03-05 | E-GEOD-44906 | biostudies-arrayexpress