endothelin-1 and Cognitive-Dysfunction

Vascular risk factors, including inflammation, may contribute to dementia development. We investigated the associations between peripheral inflammatory biomarkers and cognitive decline in five domains (memory, construction, language, psychomotor speed, and executive function).. Community-dwelling older adults from the Ginkgo Evaluation of Memory Study (n = 1,159, aged 75 or older) free of dementia at baseline were included and followed for up to 7 years. Ten biomarkers were measured at baseline representing different sources of inflammation: vascular inflammation (pentraxin 3 and serum amyloid P), endothelial function (endothelin-1), metabolic function (adiponectin, resistin, and plasminogen activating inhibitor-1), oxidative stress (receptor for advanced glycation end products), and general inflammation (interleukin-6, interleukin-2, and interleukin-10). A combined z-score was created from these biomarkers to represent total inflammation across these sources. We utilized generalized estimating equations that included an interaction term between z-scores and time to assess effect of inflammation on cognitive decline, adjusting for demographics (such as age, race/ethnicity, and sex), cardiovascular risk factors, and apolipoprotein E ε4 carrier status. A Bonferroni-adjusted significance level of .01 was used. We explored associations between individual biomarkers and cognitive decline without adjustment for multiplicity.. The combined inflammation z-score was significantly associated with memory and psychomotor speed (p < .01). Pentraxin 3, serum amyloid P, endothelin-1, and interleukin-2 were associated with change in at least one cognitive domain (p < .05).. Our results suggest that total inflammation is associated with memory and psychomotor speed. In particular, systemic inflammation, vascular inflammation, and altered endothelial function may play roles in domain-specific cognitive decline of nondemented individuals.

Topics: Adiponectin; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Cognitive Dysfunction; Endothelin-1; Endothelium, Vascular; Female; Follow-Up Studies; Humans; Inflammation; Interleukins; Male; Neuropsychological Tests; Plasminogen Activator Inhibitor 1; Receptor for Advanced Glycation End Products; Resistin; Serum Amyloid P-Component

The study aimed to investigate the plasma apolipoprotein A-1 (ApoA-1) and endothelin -1 (ET-1) changes in early Parkinson disease (PD), and analyze their relationship with cognitive function and cerebral white matter structure (WMS) change. 76 early PD patients were selected as group PD, and 30 cases of healthy persons were selected as control group. They all scanned with magnetic resonance imaging (MRI) diffusion tensor. The ApoA-1, ET-1, WMS changes, and Montreal Cognitive Assessment (MoCA) scores were recorded in the two groups of subjects. The results revealed that ApoA-1 level and Mo CA score in PD group decreased, FA value in bilateral temporal lobe, left anterior cingulate tract, corpus callosum, and other cerebral WMS area in PD group were also decreased, and ET-1 level in PD group increased (P<0.05). Compared with those of PD group patients with Mo CA≥26, plasma ApoA-1 levels and cerebral WMS FA values of the patients with Mo CA<26 were decreased, (P<0.05); the MoCA score of PD group was positively correlated with the cerebral WMS FA values (P<0.05). In short, the ApoA-1 level in patients with early PD decreased, while the ET-1 level increased, and both were related to cognitive function and WMS.

Topics: Aged; Apolipoprotein A-I; Case-Control Studies; Cognition; Cognitive Dysfunction; Diffusion Tensor Imaging; Endothelin-1; Female; Humans; Male; Mental Status and Dementia Tests; Middle Aged; Parkinson Disease; White Matter

Topics: Animals; Blood Glucose; Cell Hypoxia; Cell Line; Cognitive Dysfunction; Culture Media; Diabetes Complications; Disease Models, Animal; Endothelin-1; Humans; Inflammation; Ischemic Stroke; Lipopolysaccharides; Mice; Microglia; Signal Transduction

The endothelin (ET) system has been implicated to contribute to the pathophysiology of cognitive impairment and stroke in experimental diabetes. Our goals were to test the hypotheses that (1) circulating and (or) periinfarct ET-1 levels are elevated after stroke in both sexes and this increase is greater in diabetes, (2) ET receptors are differentially regulated in the diabetic brain, (3) brain microvascular endothelial cells (BMVEC) of female and male origin express the ETA receptor subtype, and (4) diabetes- and stroke-mimicking conditions increase ET-1 levels in BMVECs of both sexes. Control and diabetic rats were randomized to sham or stroke surgery. BMVECs of male (hBEC5i) and female (hCMEC/D3) origin, cultured under normal and diabetes-mimicking conditions, were exposed to normoxia or hypoxia. Circulating ET-1 levels were higher in diabetic animals and this was more pronounced in the male cohort. Stroke did not further increase plasma ET-1. Tissue ET-1 levels were increased after stroke only in males, whereas periinfarct ET-1 increased in both control and diabetic females. Male BMVECs secreted more ET-1 than female cells and hypoxia increased ET-1 levels in both cell types. There was sexually dimorphic regulation of ET receptors in both tissue and cell culture samples. There are sex differences in the stroke- and diabetes-mediated changes in the brain ET system at the endothelial and tissue levels.

Topics: Animals; Brain; Cell Line; Cognitive Dysfunction; Diabetes Mellitus, Experimental; Diet, High-Fat; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Female; Humans; Ischemic Stroke; Male; Microvessels; Rats; Rats, Wistar; Receptor, Endothelin A; Receptor, Endothelin B; Sex Factors; Streptozocin

Stroke patients often suffer from delayed disturbances of mood and cognition. In rodents, the prefrontal cortex (PFC) is involved in both higher order cognition and emotion. Our objective was to determine if bilateral focal ischaemic lesions restricted to the medial prefrontal cortex (mPFC) could be used to model post-stroke anxiety and/or cognitive deficits.. Groups of adult male Sprague-Dawley rats (n=9) received bilateral injections of either endothelin-1 (ET-1) (400 pmol) or vehicle (artificial cerebrospinal fluid) into the mPFC and were tested at various times using both a test of temporal order memory and in an elevated plus maze. Lesions were verified histologically.. ET-1 lesioned rats had reduced mobility on post-surgery day 8 that had resolved by day 29 at which time they spent significantly more time in the closed arm of the plus maze CONCLUSION: We conclude that ischaemic lesions localised to the mPFC can be used to model post-stroke anxiety in rats.

Topics: Animals; Anxiety; Behavior, Animal; Brain Ischemia; Cognitive Dysfunction; Disease Models, Animal; Endothelin-1; Male; Maze Learning; Memory; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Stroke