Human amnion epithelial cell therapy reduces hypertension-induced vascular stiffening and cognitive impairment
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1041469 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26856118_1.fastq.gz | Fastqsanger.gz | |||
| SRR26856118_2.fastq.gz | Fastqsanger.gz | |||
| SRR26856119_1.fastq.gz | Fastqsanger.gz | |||
| SRR26856119_2.fastq.gz | Fastqsanger.gz | |||
| SRR26856120_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:We investigated the effect of amnion epithelial cells on hypertension-induced transcriptomic changes in the brain
2023-12-30 | GSE248059 | GEO
Project description:Arterial hypertension is a leading cause of cognitive impairment, attributed to hemodynamic insufficiency, blood-brain barrier disruption, and white matter damage. However, the molecular mechanisms by which hypertension affects brain cells remain unclear. Using scRNA-seq in a mouse model of hypertension induced by angiotensin II, we mapped neocortical transcriptomic changes before (3 days) and after (42 days) onset of neurovascular and cognitive deficits. Surprisingly, evidence of endothelial transport disruption and senescence, stalled oligodendrocyte differentiation, interneuronal hypofunction and network imbalance emerged after just 3 days. By 42 days, when cognitive impairment becomes apparent, deficits in myelination and axonal conduction, as well as neuronal mitochondrial dysfunction, developed. These findings reveal a previously unrecognized early vulnerability of endothelial cells, interneurons, and oligodendrocytes, and provide the molecular bases for the subsequent neurovascular dysfunction and cognitive impairment in hypertension. In addition, the data constitute a valuable resource for future mechanistic studies and therapeutic target validation.
2025-04-17 | GSE294795 | GEO
Project description:Vascular inflammation and fibrosis are hallmarks of hypertension and contribute to the development of cardiovascular disease and cognitive impairment. However, current anti-hypertensive drugs do not treat the underlying tissue damage, such as inflammation-associated fibrosis. Human amnion epithelial cells have several properties amenable for treating vascular pathology. This study tested the effect of amnion epithelial cells on vascular pathology and cognitive impairment during hypertension. Male C57Bl6 mice (8-12 weeks) were administered vehicle (saline; n = 58) or angiotensin II (0.7 mg/kg/d, n = 56) subcutaneously for 14 d. After surgery, a subset of mice were injected with 106 amnion epithelial cells intravenously. Angiotensin II infusion increased systolic blood pressure, aortic pulse wave velocity, accumulation of aortic leukocytes, and aortic mRNA expression of collagen subtypes compared to vehicle-infused mice (n = 9-11, P < 0.05). Administration of amnion epithelial cells attenuated these effects of angiotensin II (P < 0.05). Angiotensin II-induced cognitive impairment was prevented by amnion epithelial cell therapy (n = 7-9, P < 0.05). In the brain, amnion epithelial cells modulated some of the inflammatory genes that angiotensin II promoted differential expression of (n = 6, p-adjusted < 0.05). These findings suggest that amnion epithelial cells could be explored as a potential therapy to inhibit vascular pathology and cognitive impairment during hypertension.
| S-EPMC10800338 | biostudies-literature
Project description:Hypertension (HTN) has been associated with cerebrovascular dysfunction and cognitive impairment. To understand how HTN affects the brain, the coupling between oxygen consumption and cerebral blood flow in multiple brain regions was firstly analyzed using functional MRI, in patients with HTN and healthy controls. It indicated less functional hyperemia in the cortical areas of HTN group, but showed no difference in their hippocampus. We then used deoxycorticosterone acetate (DOCA)-salt model, in which HTN is developed via sympathetic overactivity, and confirmed HTN-associated cognitive decline and reduction in functional hyperemia of pia arterioles in both male and female mice. Notably, maze test-based cognitive function was partially protected in female mice. In the sensory cortex and hippocampus of male HTN mice, we detected higher reactiveness of glial cells, compared to sham controls. But microglia in the hippocampus reacted more to DOCA-salt, showing a sub-population characterized by high expression of Apoe, B2m, Ramp1, and S100a8/a9, which was not detected in the cortex. With further analyzing the gene profile of immune cells, it revealed disease-associated types of monocyte and macrophage only in the hippocampus, and pinpointed an involvement of peripheral reservoir of immune cells. Next, to determine possible contribution from sympathetic agitation of the peripheral immune system, we tested mice lacking neuron-expressed type 1 angiotensin-II receptors (AT1R), a line that previously showed blunted sympathoexcitation under DOCA-salt treatment. In addition to improved cognitive function, DOCA-salt-induced upregulation of glial reactiveness and pro-inflammatory markers were not seen, and Bdnf expression was preserved in the hippocampus of those mice. To test the role of spleen, which deployed leukocytes upon splenic sympathoexcitation in DOCA-salt HTN, splenectomy was performed and it attenuated hippocampal inflammation and cognitive impairment, in a similar manner as neuronal AT1R knockout. Together, our data provide evidence that the cortex and hippocampus were differently affected by HTN, and proposed a neural mechanism for HTN-associated cognitive impairment that involves sympathoexcitation-induced immune response, thus highlighting that autonomic regulation of the immune system could be a therapeutic target for improving hippocampal health during HTN.
2025-11-18 | GSE255082 | GEO
Project description:Ginsenoside CK improves cognitive impairment
| PRJNA916218 | ENA
Project description:Hypertension promotes hippocampal inflammation and cognitive impairment via sympathetic activation of peripheral immune system
| PRJNA1073482 | ENA
Project description:Alzheimer case-control samples originate from the EU funded AddNeuroMed Cohort, which is a large cross-European AD biomarker study relying on human blood as the source of RNA. The design is case-control. Cases are either Alzheimer's disease patients, subjects with mild cognitive impairment or age and gender matched controls.
2015-08-05 | E-GEOD-63061 | biostudies-arrayexpress
Project description:Hypertension is a major risk factor for both stroke and cognitive impairment, but it is unclear whether it may specifically affect post-stroke cognitive impairment. We assessed the effect of hypertension and/or stroke on brain injury, cognitive outcome, and the brain transcriptomic profile. C57BL/6J mice (n=117; 3-5 mo.) received s.c. infusion of either saline or angiotensin II (for 14 d or 28 d) followed by sham surgery or photothrombotic stroke targeting the prefrontal cortex seven days later. Cognitive function was assessed with the Barnes maze. RNA sequencing was used to quantify transcriptomic changes in the brain. Angiotensin II treatment produced spontaneous hemorrhaging on the stroke brain. In the Barnes maze, hypertensive mice that received stroke surgery had an increased escape latency compared to other groups (day 3: hypertensive + stroke=166.6±6.0 s vs. hypertensive + sham=122.8±13.8 s vs. normotensive + stroke=139.9±10.1 s vs. normotensive + sham=101.9±16.7 s), consistent with a greater learning impairment. RNA sequencing revealed >800 differentially expressed genes related to neuroinflammation in hypertensive + stroke vs. hypertensive + sham, which included genes associated with apoptosis, microRNAs, autophagy, anti-cognitive biomarkers and Wnt signaling. The combination of hypertension and stroke resulted in greater learning impairment and brain injury.
2024-11-27 | GSE247789 | GEO
Project description:It is important to maintain cognitive integrity during underwater operations, which may also trigger cognitive alterations. Cognitive effect of underwater operations and the underlying mechanism remain elusive. Here, we found a single underwater operation affects cognition in a time-dependent model. Prolonged exposure elicits significant cognitive impairment and hippocampal dysfunction, which was accompanied by activation of microglia and upregulation of pro-inflammatory cytokines. RNA-sequencing supported the involvement of neuroinflammation and indicated the critical role of CCR3. Knockdown of CCR3 significantly rescued cognitive impairment and hippocampal dysfunction. Furthermore, the upregulation of pro-inflammatory cytokines was also reversed. Mechanistically, CCR3 knockdown switched the activated microglia from a pro-inflammatory to neuroprotective phenotype. Taken together, these results highlighted the time-dependent effects of a single underwater operation on cognitive function. Knocking down CCR3 can attenuate neuroinflammation by regulating polarization of activated microglia, thereby alleviating prolonged underwater operation-induced cognitive impairment.
2024-05-20 | GSE247651 | GEO
Project description:Persistent central nervous system (CNS) immune dysregulation and consequent dysfunction of multiple neural cell types is central to the neurobiological underpinnings of a cognitive impairment syndrome, colloquially referred to as “brain fog”, that can occur following traditional cancer therapies or certain infections. Immunotherapies have revolutionized cancer care for many tumor types, but the potential long-term cognitive sequelae are incompletely understood. Here, we demonstrate in mouse models that chimeric antigen receptor (CAR) T-cell therapy for both CNS and non-CNS cancers can impair cognitive function and induce a persistent CNS immune response characterized by white matter microglial reactivity, microglial chemokine expression, and elevated cerebrospinal fluid (CSF) cytokines and chemokines. Consequently, oligodendroglial homeostasis and hippocampal neurogenesis are disrupted. Single nucleus sequencing studies of human frontal cortex and subcortical white matter from brain tumor patients with or without previous CAR T-cell therapy confirm reactive states of microglia and oligodendrocytes in patients treated with CAR T cell therapy. In mice, transient microglial depletion or CCR3 chemokine receptor blockade rescues oligodendroglial deficits and cognitive performance in a behavioral test of attention and short-term memory function following CAR T-cell therapy. Taken together, these findings illustrate similar mechanisms underlying immunotherapy-related cognitive impairment (IRCI) and cognitive impairment following traditional cancer therapies and other immune challenges.
2025-02-18 | GSE286221 | GEO