scholarly journals Mitochondrial Perturbation Contributing to Cognitive Decline in Streptozotocin-Induced Type 1 Diabetic Rats

2018 ◽  
Vol 46 (4) ◽  
pp. 1668-1682 ◽  
Author(s):  
Yu Zhou ◽  
Siheng Lian ◽  
Jin Zhang ◽  
Donghai Lin ◽  
Caihua Huang ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Metabolic Pathways ◽  
Mitochondrial Dynamics ◽  
Diabetic Rats ◽  
Morris Water Maze Test ◽  
Mitochondrial Morphology ◽  
Underlying Mechanisms ◽  
And Function ◽  
Energy Failure

Background/Aims: Mitochondrial perturbation is a well-established cause of cognitive decline, but as yet it is unclear how mitochondria-associated neuronal abnormalities in type 1 diabetic (T1DM) brain contribute to cognitive decline. Methods: The streptozotocin (STZ)-induced mouse model of T1DM was used. The Morris water maze test was applied to assess the effect of T1DM on learning and memory. We detected changes in mitochondrial morphology, function and dynamics. Furthermore, we employed metabolomic analysis to reveal the underlying mechanisms of mitochondrial perturbation which contribute to cognitive decline. Results: Our results show that T1DM impairs mitochondrial dynamics, morphology and function in neurons, associated with a decline in cognitive ability. Metabolomic analyses revealed that T1DM mainly affects metabolic pathways involved in mitochondrial energy failure and impairs the antioxidative system. Conclusion: These results lay the basis for understanding the underlying mitochondria-associated causes of T1DM-associated cognitive decline and may provide a potential treatment strategy for this condition in future.

scholarly journals A comprehensive approach for artifact-free sample preparation and assessment of mitochondrial morphology in tissue and cultured cells

2021 ◽  
Author(s):  
Antentor Hinton ◽  
Prasanna Katti ◽  
Trace A. Christensen ◽  
Margaret Mungai ◽  
Jianqiang Shao ◽  
...  
Keyword(s):  
Structural Changes ◽  
Cultured Cells ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Morphology ◽  
Specimen Preparation ◽  
Preparation Methods ◽  
Cellular Environment ◽  
Stress Changes ◽  
Precise Relationship ◽  
And Function

Mitochondrial dynamics and morphology (fission, fusion, and the formation of nanotunnels) are very sensitive to the cellular environment and may be adversely affected by oxidative stress, changes in calcium levels, and hypoxia. Investigating the precise relationship between the organelle structure and function requires methods that can adequately preserve the structure while providing accurate, quantitative measurements of mitochondrial morphological attributes. Here, we demonstrate a practical approach for preserving and measuring fine structural changes in two-dimensional electron micrographs, obtained using transmission electron microscopy, highlighting the specific advantages of this technique. Additionally, this study defines a set of quantifiable metrics that can be applied to measure mitochondrial architecture and other organellar structures. Finally, we validated specimen preparation methods that avoid the introduction of morphological artifacts in mitochondrial appearance that do not require whole-animal perfusion.

scholarly journals Supplementation of Type 1 Diabetic Rats with Carrot Powder Lowers Blood Glucose without Improving Cardiac Structure and Function

2018 ◽  
Vol 23 (2) ◽  
pp. 115-121
Author(s):  
Xavier Lieben Louis ◽  
Pema Raj ◽  
Kathleen J. McClinton ◽  
Liping Yu ◽  
Miyoung Suh ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Diabetic Rats ◽  
Structure And Function ◽  
Cardiac Structure ◽  
Cardiac Structure And Function ◽  
And Function

Mitochondrial Injury and Targeted Intervention in Septic Cardiomyopathy

2019 ◽  
Vol 25 (18) ◽  
pp. 2060-2070 ◽  
Author(s):  
Ying Tan ◽  
Sainan Chen ◽  
Jiankai Zhong ◽  
Jun Ren ◽  
Maolong Dong
Keyword(s):  
Clinical Work ◽  
Multiple Organ ◽  
Mitochondrial Morphology ◽  
Septic Cardiomyopathy ◽  
Mitochondrial Injury ◽  
Main Culprit ◽  
Cardiac Contractile Dysfunction ◽  
Underlying Mechanisms ◽  
Sepsis And Septic Shock ◽  
And Function

Background: Sepsis and septic shock are known to prompt multiple organ failure including cardiac contractile dysfunction, which is typically referred to as septic cardiomyopathy. Among various theories postulated for the etiology of septic cardiomyopathy, mitochondrial injury (both morphology and function) in the heart is perceived as the main culprit for reduced myocardial performance and ultimately heart failure in the face of sepsis. Methods: Over the past decades, ample of experimental and clinical work have appeared, focusing on myocardial mitochondrial changes and related interventions in septic cardiomyopathy. Results and Conclusion: Here we will briefly summarize the recent experimental and clinical progress on myocardial mitochondrial morphology and function in sepsis, and discuss possible underlying mechanisms, as well as the contemporary interventional options.

P3-315 Synaptic AMPA receptor dysfunction: a mechanism for cognitive decline in type-1-diabetic rats

2004 ◽  
Vol 25 ◽  
pp. S444-S445
Author(s):  
Thirumalini Vaithianathan ◽  
Deepa Bedi ◽  
Kanju M. Patrick ◽  
Kodeeswaran Parameshwaran ◽  
Lori L. McMahon ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Ampa Receptor ◽  
Diabetic Rats

scholarly journals Losartan Reverses Hippocampal Increase of Kynurenic Acid in Type 1 Diabetic Rats: A Novel Procognitive Aspect of Sartan Action

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Iwona Chmiel-Perzyńska ◽  
Adam Perzyński ◽  
Bartosz Olajossy ◽  
Paulina Gil-Kulik ◽  
Janusz Kocki ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Kynurenic Acid ◽  
De Novo ◽  
Neuroprotective Effect ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Expression Of Genes ◽  
Genes Encoding

Patients with diabetes mellitus (DM) type 1 and 2 are at a higher risk of cognitive decline and dementia; however, the underlying pathology is poorly understood. Kynurenic acid (KYNA), endogenous kynurenine metabolite, displays pleiotropic effects, including a blockade of glutamatergic and cholinergic receptors. Apart from well-known glial origin, kynurenic acid is robustly synthesized in the endothelium and its serum levels correlate with homocysteine, a risk factor for cognitive decline. Studies in an experimental DM model suggest that a selective, hippocampal increase of the kynurenic acid level may be an important factor contributing to diabetes-related cognitive impairment. The aim of this study was to assess the effects of chronic, four-week administration of losartan, angiotensin receptor blocker (ARB), on the brain KYNA in diabetic rats. Chromatographic and rt-PCR techniques were used to measure the level of KYNA and the expression of genes encoding kynurenine aminotransferases, KYNA biosynthetic enzymes, in the hippocampi of rats with streptozotocin-induced DM, treated with losartan. The effect of losartan on KYNA synthesis de novo was also evaluated in vitro, in brain cortical slices. The hippocampal increase of KYNA content occurred in diabetic rats treated and nontreated with insulin. Losartan did not affect KYNA levels when administered per se to naïve or diabetic animals but normalized KYNA content in diabetic rats receiving concomitantly insulin. The expression of CCBL1 (kat 1), AADAT (kat 2), and KAT3 (kat 3) genes did not differ between analyzed groups. Low concentrations of losartan did not affect KYNA production in vitro. The neuroprotective effect of ARBs in diabetic individuals may be, at least partially, linked to modulation of KYNA metabolism. The ability of ARB to modulate synthesis of KYNA in diabetic brain does not seem to result from changed expression of genes encoding KATs. We propose possible involvement of angiotensin AT4 receptors in the observed action of losartan.

Defective intracellular Ca2+ signaling contributes to cardiomyopathy in Type 1 diabetic rats

2002 ◽  
Vol 283 (4) ◽  
pp. H1398-H1408 ◽  
Author(s):  
Kin M. Choi ◽  
Yan Zhong ◽  
Brian D. Hoit ◽  
Ingrid L. Grupp ◽  
Harvey Hahn ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
Diabetic Rat ◽  
Channel Current ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Rat Myocytes ◽  
Systolic And Diastolic Function ◽  
And Function ◽  
Contraction And Relaxation

The goal of the study was to determine whether defects in intracellular Ca2+ signaling contribute to cardiomyopathy in streptozotocin (STZ)-induced diabetic rats. Depression in cardiac systolic and diastolic function was traced from live diabetic rats to isolated individual myocytes. The depression in contraction and relaxation in myocytes was found in parallel with depression in the rise and decline of intracellular free Ca2+ concentration ([Ca2+]i). The sarcoplasmic reticulum (SR) Ca2+ store and rates of Ca2+ release and resequestration into SR were depressed in diabetic rat myocytes. The rate of Ca2+ efflux via sarcolemmal Na+/Ca2+ exchanger was also depressed. However, there was no change in the voltage-dependent L-type Ca2+ channel current that triggers Ca2+ release from the SR. The depression in SR function was associated with decreased SR Ca2+-ATPase and ryanodine receptor proteins and increased total and nonphosphorylated phospholamban proteins. The depression of Na+/Ca2+ exchanger activity was associated with a decrease in its protein level. Thus it is concluded that defects in intracellular Ca2+ signaling caused by alteration of expression and function of the proteins that regulate [Ca2+]i contribute to cardiomyopathy in STZ-induced diabetic rats. The increase in phospholamban, decrease in Na+/Ca2+ exchanger, and unchanged L-type Ca2+ channel activity in this model of diabetic cardiomyopathy are distinct from other types of cardiomyopathy.

scholarly journals Skeletal Muscle Health and Cognitive Function: A Narrative Review

2020 ◽  
Vol 22 (1) ◽  
pp. 255
Author(s):  
Sophia X. Sui ◽  
Lana J. Williams ◽  
Kara L. Holloway-Kew ◽  
Natalie K. Hyde ◽  
Julie A. Pasco
Keyword(s):  
Risk Factors ◽  
Skeletal Muscle ◽  
Cognitive Decline ◽  
Targeted Interventions ◽  
Lifestyle Risk Factors ◽  
Muscle Health ◽  
Lifestyle Risk ◽  
Underlying Mechanisms ◽  
And Function ◽  
The Relationship

Sarcopenia is the loss of skeletal muscle mass and function with advancing age. It involves both complex genetic and modifiable risk factors, such as lack of exercise, malnutrition and reduced neurological drive. Cognitive decline refers to diminished or impaired mental and/or intellectual functioning. Contracting skeletal muscle is a major source of neurotrophic factors, including brain-derived neurotrophic factor, which regulate synapses in the brain. Furthermore, skeletal muscle activity has important immune and redox effects that modify brain function and reduce muscle catabolism. The identification of common risk factors and underlying mechanisms for sarcopenia and cognition may allow the development of targeted interventions that slow or reverse sarcopenia and also certain forms of cognitive decline. However, the links between cognition and skeletal muscle have not been elucidated fully. This review provides a critical appraisal of the literature on the relationship between skeletal muscle health and cognition. The literature suggests that sarcopenia and cognitive decline share pathophysiological pathways. Ageing plays a role in both skeletal muscle deterioration and cognitive decline. Furthermore, lifestyle risk factors, such as physical inactivity, poor diet and smoking, are common to both disorders, so their potential role in the muscle–brain relationship warrants investigation.

scholarly journals SLC40A1 mediates ferroptosis and cognitive dysfunction in type 1 diabetes

2020 ◽  
Author(s):  
Lijun Hao ◽  
Jun Mi ◽  
Liping Song ◽  
Yinnan Guo ◽  
Yanli Li ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cognitive Dysfunction ◽  
Low Frequency ◽  
Latency Period ◽  
Diabetic Rats ◽  
Blood Oxygenation ◽  
Morris Water Maze Test ◽  
Diabetic Rat ◽  
Dependent Signal

Abstract Objective: Cognitive dysfunction often accompanies diabetes. Both hypoglycemia and hyperglycemia cause cognitive dysfunctions. However, the underlying pathophysiology remains unclear. Recent evidence show that ferroptosis primarily triggers nerve cell death, Alzheimer's disease (AD), Huntington’s disease (HD), and Parkinson's disease (PD). We purposed to investigate whether ferroptosis is a vital pathogenic pathway in diabetes-induced cognitive dysfunction. Methods and results: Type 1 diabetic rat model was created by intraperitoneal injection of streptozotocin (STZ). Significant cognitive dysfunction was observed in the diabetic rats as evidenced by increase in latency period to find a hidden platform and decreased cumulative time spent in the target quadrant in the Morris water maze test. We detected the amplitude of low-frequency fluctuation (ALFF) of the BOLD (Blood Oxygenation Level-Dependent) signal using resting-state functional magnetic resonance imaging (rs-fMRI). Consequently, we found that the ALFF values, as well as the T2 relaxation time of the bilateral hippocampus, were reduced in Type 1 diabetic rats. We detected Fe2+ level and lipid peroxidation products (MDA and 4-HNE) in the hippocampus. Mitochondria and neuron injury in the STZ-induced diabetic rats were determined using a Transmission Electron Microscope and Nissl body staining. Iron overload and ferroptosis were detected in the hippocampus. Furthermore, mRNA microarray analysis revealed 201 dysregulated mRNAs in STZ-induced type 1 diabetes (T1D). Pathway enrichment analyses indicated that differentially expressed mRNAs associated-coding genes were associated with ferroptosis. Among ferroptosis signaling pathway genes, Slc40a1 gene (ferroportin) was downregulated.Conclusion: We show that ferroptosis is associated with diabetic cognitive dysfunction and Slc40a1 mediates ferroptosis in Type 1 diabetes.

scholarly journals Amyloid-Beta1-42 -Induced Increase in GABAergic Tonic Conductance in Mouse Hippocampal CA1 Pyramidal Cells

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 693 ◽  
Author(s):  
Beatriz Calvo-Flores Guzmán ◽  
SooHyun Kim ◽  
Bhavya Chawdhary ◽  
Katie Peppercorn ◽  
Warren P Tate ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cognitive Deficits ◽  
Gaba Receptors ◽  
Neurodegenerative Disorder ◽  
Pyramidal Cells ◽  
Gamma Aminobutyric Acid ◽  
Ca1 Region ◽  
Underlying Mechanisms ◽  
And Function

Alzheimer’s disease (AD) is a complex and chronic neurodegenerative disorder that involves a progressive and severe decline in cognition and memory. During the last few decades a considerable amount of research has been done in order to better understand tau-pathology, inflammatory activity and neuronal synapse loss in AD, all of them contributing to cognitive decline. Early hippocampal network dysfunction is one of the main factors associated with cognitive decline in AD. Much has been published about amyloid-beta1-42 (Aβ1-42)-mediated excitotoxicity in AD. However, increasing evidence demonstrates that the remodeling of the inhibitory gamma-aminobutyric acid (GABAergic) system contributes to the excitatory/inhibitory (E/I) disruption in the AD hippocampus, but the underlying mechanisms are not well understood. In the present study, we show that hippocampal injection of Aβ1-42 is sufficient to induce cognitive deficits 7 days post-injection. We demonstrate using in vitro whole-cell patch-clamping an increased inhibitory GABAergic tonic conductance mediated by extrasynaptic type A GABA receptors (GABAARs), recorded in the CA1 region of the mouse hippocampus following Aβ1-42 micro injection. Such alterations in GABA neurotransmission and/or inhibitory GABAARs could have a significant impact on both hippocampal structure and function, causing E/I balance disruption and potentially contributing to cognitive deficits in AD.

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