angiotensin-i and Cognition-Disorders

To explore effects of the brain renin-angiotensin system (RAS) on cognition.. Systematic review of experimental (non-human) studies assessing cognitive effects of RAS peptides angiotensin-(3-8) [Ang IV] and angiotensin-(1-7) [Ang-(1-7)] and their receptors, the Ang IV receptor (AT4R) and the Mas receptor.. Of 450 articles identified, 32 met inclusion criteria. Seven of 11 studies of normal animals found Ang IV had beneficial effects on tests of passive or conditioned avoidance and object recognition. In models of cognitive deficit, eight of nine studies found Ang IV and its analogs (Nle. Studies of cognitive impairment show salutary effects of acute administration of Ang IV and its analogs, as well as AT4R activation. Brain RAS peptides appear most effective administered intracerebroventricularly, close to the time of learning acquisition or retention testing. Ang-(1-7) shows anti-dementia qualities.

Topics: Angiotensin I; Angiotensin II; Animals; Cognition Disorders; Databases, Bibliographic; Dementia; Disease Models, Animal; Humans; Memory, Short-Term; Peptide Fragments

Brain angiotensin-(1-7) (Ang-(1-7)) concentration has been shown to be reduced and inversely correlated with tau pathology in a mouse model of Alzheimer's disease (AD). In this study, to determine whether the concentration of Ang-(1-7) and the activity of its converting enzyme angiotensin-converting enzyme 2 were altered in plasma under AD context, the plasma samples from 110 AD patients and 128 age- and gender-matched controls were screened. In AD patients, the plasma concentration of Ang-(1-7) was significantly reduced (15.63±4.35pg/mL vs. 19.58±3.22pg/mL, P<0.001) and positively correlated with cognitive functions (R=0.66, P<0.001). Meanwhile, receiver-operating characteristic analysis showed that the Ang-(1-7) concentration in plasma could distinguish AD patients from controls with the sensitivity and specificity of 69.1% and 74.2%, respectively, when the optimal cut-off value (18.2 pg/mL) was chosen. These findings indicate that plasma Ang-(1-7) may represent a potential biomarker for AD diagnosis, and further suggest an involvement of this heptapeptide in the pathogenesis of this disease.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Angiotensin I; Angiotensin-Converting Enzyme 2; Area Under Curve; Biomarkers; Case-Control Studies; Cognition Disorders; Female; Humans; Male; Neuropsychological Tests; Peptide Fragments; Peptidyl-Dipeptidase A; Psychiatric Status Rating Scales; Sensitivity and Specificity; Statistics as Topic

This work was performed to test our hypothesis that angiotensin-(1-7) can ameliorate cognitive impairment and cerebrovascular reactivity in 5XFAD mice, a useful model of Alzheimer's disease. 5XFAD mice received intracerebroventricular infusion of (1) vehicle, (2) angiotensin-(1-7), or (3) angiotensin-(1-7)+A779, a specific Mas receptor antagonist, for 4 weeks. Angiotensin-(1-7), through Mas receptor, significantly ameliorated cognitive impairment in 5XFAD mice. As estimated by acetazolamide-induced increase in cerebral blood flow, angiotensin-(1-7), through Mas receptor, enhanced cerebrovascular reactivity in 5XFAD mice. In conclusion, angiotensin-(1-7)/Mas receptor axis improves cognitive function and cerebrovascular function in a mouse model of Alzheimer's disease.

Topics: Acetazolamide; Alzheimer Disease; Amyloid beta-Peptides; Angiotensin I; Animals; Avoidance Learning; Carbonic Anhydrase Inhibitors; Cerebrovascular Circulation; Cognition Disorders; Disease Models, Animal; Drug Delivery Systems; Infusions, Intraventricular; Maze Learning; Memory Disorders; Mice; Mice, Transgenic; Peptide Fragments; Reaction Time; tau Proteins

To explore the effects of angiotensin-(1-7) on the learning and memory abilities and the expressions of glial fibrillary acidic protein (GFAP) and glial cell line-derived neurotrophic factor (GDNF) in the hippocampus of diabetic rats.. Forty male SD rats were randomly assigned into 4 groups, namely the control group, diabetic group, Ang(1-7)-treated diabetic group (DM1 group), and Ang-(1-7)- and Mas receptor antagonist A779-treated diabetic group (DM2 group). Diabetic rat models were established by a single intraperitoneal injection of streptozotocin (60 mg/kg). The cognitive function of the rats was assessed with Morris water maze (MWM) test. The expressions of GDNF in the hippocampus were examined by RT-PCR and Western blot. Nissl staining was performed to evaluate the morphological changes in rat hippocampus. The expressions of glial fibrillary acidic protein (GFAP, a key indicator of astrocytic reactivity) and caspase-3 were measured by immunohistochemistry.. Compared with the control group, the diabetic rats exhibited significantly impaired learning and memory abilities (P<0.05) with lowered expression of GDNF and increased caspase-3 expression in the hippocampus (P<0.05) and significant hippocampal neuronal and astrocyte injuries (P<0.05). Treatment with Ang(1-7) obviously improved the learning and memory abilities of the diabetic rats (P<0.05), increased GDNF and GFAP expressions (P<0.05), lowered caspase-3 expression (P<0.05), and increased the number of surviving neurons in the hippocampus (P<0.05). Such effects of Ang(1-7) effect was blocked by treatment with A779 of the diabetic rats.. Ang(1-7) can alleviate cognitive dysfunction in diabetic rats possibly by up-regulating the expressions of GFAP and GDNF and promoting neuron survival in the hippocampus.

Topics: Angiotensin I; Animals; Astrocytes; Caspase 3; Cognition; Cognition Disorders; Diabetes Mellitus, Experimental; Glial Cell Line-Derived Neurotrophic Factor; Glial Fibrillary Acidic Protein; Hippocampus; Male; Memory; Neurons; Peptide Fragments; Rats; Rats, Sprague-Dawley; Streptozocin

Chronic cerebral hypoperfusion (CCH) is associated with cognitive decline in aging, vascular dementia and Alzheimer׳s disease. Recently, angiotensin-(1-7) (Ang-(1-7)), one of the physiological constituents of the brain, was found to protect against cognitive dysfunction and brain ischemia. However, the effects of Ang-(1-7) on CCH-induced cognitive deficits remained unknown. In the present study, Ang-(1-7) significantly alleviated CCH-induced cognitive deficits in rats subjected to permanent bilateral occlusion of the common carotid arteries (a model of CCH). This neuroprotective effect was associated with increased nitric oxide generation, attenuated neuronal loss and suppressed astrocyte proliferation in the hippocampus. These findings demonstrate that Ang-(1-7) is a promising therapeutic agent for CCH-induced cognitive deficits.

Topics: Angiotensin I; Animals; Astrocytes; Blood Pressure; Brain Ischemia; Carotid Artery, Common; Cell Death; Cell Proliferation; Chronic Disease; Cognition Disorders; Disease Models, Animal; Hippocampus; Male; Maze Learning; Neurons; Neuroprotective Agents; Nitric Oxide; Peptide Fragments; Rats, Wistar

We hypothesized that chronic administration of the angiotensin-converting enzyme inhibitor, ramipril, to young adult male rats would prevent/ameliorate fractionated whole-brain irradiation-induced perirhinal cortex-dependent cognitive impairment. Eighty 12-14-week-old young adult male Fischer 344 rats received either: (1) sham irradiation, (2) 40 Gy of fractionated whole-brain irradiation delivered as two 5 Gy fractions/week for 4 weeks, (3) sham irradiation plus continuous administration of 15 mg/L of ramipril in the drinking water starting 3 days before irradiation, or (4) fractionated whole-brain irradiation plus ramipril. Cognitive function was assessed using a perirhinal cortex-dependent version of the novel object recognition task 26 weeks after irradiation. Microglial activation was determined in the perirhinal cortex and the dentate gyrus of the hippocampus 28 weeks after irradiation using the ED1 antibody. Neurogenesis was assessed in the granular cell layer and subgranular zones of the dentate gyrus using a doublecortin antibody. Fractionated whole-brain irradiation led to: (1) a significant impairment in perirhinal cortex-dependent cognitive function, (2) a significant increase in activated microglia in the dentate gyrus but not in the perirhinal cortex, and (3) a significant decrease in neurogenesis. Continuous administration of ramipril before, during, and after irradiation prevented the fractionated whole-brain irradiation-induced changes in perirhinal cortex-dependent cognitive function, as well as in microglial activation in the dentate gyrus. Thus, as hypothesized, continuous administration of the angiotensin-converting enzyme inhibitor, ramipril, can prevent the fractionated whole-brain irradiation-induced impairment in perirhinal cortex-dependent cognitive function.

Topics: Angiotensin I; Angiotensin-Converting Enzyme Inhibitors; Animals; Body Weight; Cerebral Cortex; Cognition Disorders; Cranial Irradiation; Dose Fractionation, Radiation; Doublecortin Protein; Male; Radiation Injuries, Experimental; Ramipril; Rats; Rats, Inbred F344