Molecular and biochemical mechanisms of diabetic encephalopathy

Acta Biochimica Polonica, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 22, 2023

Diabetes mellitus is one of the important independent risk factors for development neurological disorders such as ischemic stroke, transient attacks, vascular dementia and neurodegenerative processes. Hyperglycemia plays a crucial role trigger in pathogenesis these disorders. In this review, we summarize existing data on molecular mechanisms diabetic encephalopathy development, consider features oxidative nitrosative stresses, changes thiol-disulfide system, well mitochondrial endothelial dysfunction diabetes. We focus HSP 70 cellular responses encephalopathy. HSP70 protein an component endogenous system neuroprotection. It acts intracellular chaperone, providing folding, retention, transport synthesized proteins, their degradation under both normoxic stress-induced denaturation conditions. can be considered marker promising therapeutic target treatment diabetes mellitus.

Language: Английский

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The potential role and mechanism of Rhizoma Coptidis in prevention of diabetic encephalopathy: targeting sodium ion and channels

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 14, 2025

Rhizoma Coptidis (RC) is an edible and medicinal herb with anti-hyperglycemia, which has potential application in the prevention of diabetic encephalopathy (DE). However, its efficacy underlying mechanism DE have not been elucidated yet. The objective current study to investigate preventive effect RC on DE, thereby focusing target through method network pharmacology molecular docking. Sixty 4-week-old, male C57BL/6 mice were randomly allocated six groups: control, model, metformin (200 mg/kg), RCL (0.75 g/kg), RCM (1.5 RCH (3 g/kg). DE-model induced by streptozocin combined a high-fat diet. In addition, neuroprotective was determined both vivo vitro. Network analysis used screen RC. Thereafter, action explored docking prediction Western blot analysis. An patients performed validate it from another perspective. results showed that cognitive state model improved neuronal injury ameliorated after administration. Active compounds RC, berberine coptisine, found ameliorate HT22 high glucose. suggest voltage-gated sodium channel subtypes (Nav1.1, Nav1.2, Nav1.6) may be targets for DE. Furthermore, revealed significantly upregulated Nav1.1 while Nav1.6 could not. serum related status patients, can as diagnostic index mild moderate-severe functional food or adjuvant drug prevention, Nav1.2 are promising intervention targets.

Language: Английский

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Nerolidol rescues hippocampal injury of diabetic rats through inhibiting NLRP3 inflammasome and regulation of MAPK/AKT pathway

BioFactors, Journal Year: 2024, Volume and Issue: unknown

Published: April 16, 2024

Abstract Despite the observation of diabetes‐induced brain tissue damage and impaired learning memory, underlying mechanism remains elusive, effective, targeted therapeutics are lacking. Notably, NLRP3 inflammasome is highly expressed in hippocampus diabetic individuals. Nerolidol, a naturally occurring compound with anti‐inflammatory antioxidant properties, has been identified as potential therapeutic option for metabolic disorders. However, ameliorative capacity nerolidol on hippocampal injury its remain unclear. Network pharmacology molecular docking was used to predict signaling pathways targets treatment diabetes. Then established rat model using streptozotocin (STZ) combined high‐fat diet administered. Morris water maze assess spatial memory capacity. Hematoxylin eosin Nissl staining detect neuronal hippocampus. Transmission electron microscopy extent mitochondria, endoplasmic reticulum (ER) synapses. Immunofluorescence GFAP, IBA1, expression Western blot apoptosis (Bcl‐2, BAX, Cleaved‐Caspase‐3); synapses (postsynaptic densifying protein 95, SYN1, Synaptophysin); mitochondria (DRP1, OPA1, MFN1, MFN2); ER (GRP78, ATF6, CHOP, caspase‐12); (NLRP3, ASC, caspase‐1); inflammatory cytokines (IL‐18, IL‐1β, TNF‐α); AKT (P‐AKT); mitogen‐activated kinase (MAPK) pathway (P‐ERK, P‐p38, P‐JNK) related expression. showed that nerolidol's possible mechanisms treating diabetes MAPK/AKT effects. Animal experiments demonstrated could improve blood glucose, lipids, rats. Furthermore, synaptic, mitochondrial, ultrastructure rats by potentially affecting ER‐related proteins. Further studies revealed decreased neuroinflammation, factor while also decreasing MAPK enhancing improves cannot be shown cognitive function. In conclusion, our study reveals first time can ameliorate damage, ER, mitochondrial we suggest may inhibit affected AKT. These findings provide new experimental basis use associated disease.

Language: Английский

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High glucose- or AGE-induced oxidative stress inhibits hippocampal neuronal mitophagy through the Keap1–Nrf2–PHB2 pathway in diabetic encephalopathy

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 14, 2024

Diabetic encephalopathy (DE) is a severe complication of diabetes, but its pathogenesis remains unclear. This study aimed to investigate the roles and underlying mechanisms high glucose (HG)- advanced glycosylation end product (AGE)-induced oxidative stress (OS) in cognitive decline DE. The DE mouse model was established using high-fat diet streptozotocin, functions were evaluated Morris Water Maze, novel object recognition, Y-maze test. results revealed increased reactive oxygen species (ROS) generation, mitophagy inhibition, decreased prohibitin 2 (PHB2) expression hippocampal neurons mice HG- or AGE-treated HT-22 cells. However, overexpression PHB2 reduced ROS reversed improved mitochondrial function cells ameliorated decline, structural damage, inhibition mice. Further analysis that Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related (Nrf2) pathway involved AGE-mediated downregulation These demonstrate AGE-induced OS inhibits via Keap1-Nrf2-PHB2 pathway, thereby contributing

Language: Английский

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The effectiveness of hesperidin on bisphenol A-induced spinal cord toxicity in a diabetic rat model

Toxicon, Journal Year: 2024, Volume and Issue: 243, P. 107724 - 107724

Published: April 21, 2024

Language: Английский

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Chemokine CX3CL1 (Fractalkine) Signaling and Diabetic Encephalopathy

Published: June 3, 2024

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence increasing worldwide parallel with obesity pandemic. A lack of insulin or resistance, consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) a long-term complication central nervous system (CNS), characterized by cognitive impairment motor dysfunctions. The role oxidative stress neuroinflammation pathomechanism DE has been proven. Fractalkine (CX3CL1) unique properties as an adhesion molecule chemoattractant, acting on only receptor, CX3CR1, it regulates activity microglia physiological states neuroinflammation. Depending clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects inhibiting inflammatory process or, conversely, maintaining/intensifying inflammation neurotoxicity. This review discusses evidence supporting that pair other neurotoxic. Interrupting vicious cycle within neuron-microglia interactions be therapeutic goal limiting response.

Language: Английский

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Chemokine CX3CL1 (Fractalkine) Signaling and Diabetic Encephalopathy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7527 - 7527

Published: July 9, 2024

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence increasing worldwide parallel with obesity pandemic. A lack of insulin or resistance, consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) a long-term complication central nervous system (CNS), characterized by cognitive impairment motor dysfunctions. The role oxidative stress neuroinflammation pathomechanism DE has been proven. Fractalkine (CX3CL1) unique properties as an adhesion molecule chemoattractant, acting on only receptor, CX3CR1, it regulates activity microglia physiological states neuroinflammation. Depending clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects inhibiting inflammatory process or, conversely, maintaining/intensifying inflammation neurotoxicity. This review discusses evidence supporting that pair other neurotoxic. Therefore, interrupting vicious cycle within neuron–microglia interactions promoting neurotoxic axis be therapeutic goal limiting response. However, optimal approach prevent simply tight glycemic control, because elimination dysglycemic CNS abolishes fundamental mechanisms induce this cycle.

Language: Английский

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Neuroactive Steroid–Gut Microbiota Interaction in T2DM Diabetic Encephalopathy

Biomolecules, Journal Year: 2023, Volume and Issue: 13(9), P. 1325 - 1325

Published: Aug. 29, 2023

The pathological consequences of type 2 diabetes mellitus (T2DM) also involve the central nervous system; indeed, T2DM patients suffer from learning and memory disabilities with a higher risk developing dementia. Although several factors have been proposed as possible contributors, how neuroactive steroids gut microbiome impact brain pathophysiology in remain unexplored. On this basis, male Zucker diabetic fatty (ZDF) rats, we studied whether alters abilities using novel object recognition test, steroid levels by liquid chromatography-tandem mass spectrometry, hippocampal parameters molecular assessments, composition 16S next-generation sequencing. Results obtained reveal that worsens these are correlated increased corticosterone plasma decrease allopregnanolone hippocampus, where neuroinflammation, oxidative stress, mitochondrial dysfunction were reported. Interestingly, our analysis highlighted small group taxa strictly related to both impairment levels. Overall, data underline an interesting role for microbiota may represent candidates development therapeutic strategies.

Language: Английский

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The Role of Insulin Deficiency in Cognitive Dysfunction in Patients with Type 1 Diabetes Mellitus

Fundamental and Clinical Medicine, Journal Year: 2024, Volume and Issue: 9(2), P. 94 - 102

Published: June 21, 2024

Type 1 diabetes mellitus is a chronic autoimmune disease with onset in childhood and adolescence. Neurological disorders are among the most frequent complications of type might lead to cognitive impairment termed as diabetic encephalopathy. Besides regulating blood glucose, insulin have neuroprotective pro-cognitive effects through its action on receptors brain, promoting production neurotransmitters, long-term potentiation, synaptic plasticity, neuronal differentiation. By enhancing abovementioned processes responsible for learning memory, improves functioning. Insulin deficiency triggers dysfunction encephalopathy via mitochondrial dysfunction, oxidative stress, disorganisation glucose metabolism which alter functioning transporter proteins induce pericyte loss, ultimately compromising integrity blood-brain barrier. Intranasal delivery exogenous insulin, bypasses bloodbrain barrier, may serve an efficient therapeutic strategy correcting patients Further research needed uncover understand functions mellitus.

Language: Английский

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The neuroprotective role of celastrol on hippocampus in diabetic rats by inflammation restraint, insulin signaling adjustment, Aβ reduction and synaptic plasticity alternation

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117397 - 117397

Published: Sept. 3, 2024

Celastrol, the primary constituent of Tripterygium wilfordii, has demonstrated neuroprotective properties in rats with dementia by reducing inflammation. A high-fat diet and streptozotocin injection were utilized to establish a diabetic rat model, which was then employed investigate possible protective effect celastrol against development diabetes-induced learning memory deficits. Afterwards, experimental animals received dose gavage (4 mg/kg/d). An animal study showed that enhanced insulin sensitivity glucose tolerance rats. In Morris water maze test, diabetes performed poorly terms spatial memory; treatment improved these outcomes. Additionally, administration downregulated expression inflammatory-related proteins (NF-κB, IKKα, TNF-α, IL-1β, IL-6) greatly reduced generation Aβ hippocampus tissue. Moreover, signaling pathway-related PI3K, AKT, GSK-3β significantly upregulated after administered. Also, prevented damage brain structures increased synthesis synaptic like PSD-95 SYT1. conclusion, exerts modulating system inflammatory responses, helps ameliorate cognitive impairment associated diabetes.

Language: Английский

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