Bridging metabolic syndrome and cognitive dysfunction: role of astrocytes

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Май 10, 2024

Metabolic syndrome (MetS) and cognitive dysfunction pose significant challenges to global health the economy. Systemic inflammation, endocrine disruption, autoregulatory impairment drive neurodegeneration microcirculatory damage in MetS. Due their unique anatomy function, astrocytes sense integrate multiple metabolic signals, including peripheral hormones nutrients. Astrocytes synapses engage a complex dialogue of energetic immunological interactions. act as bridge between MetS dysfunction, undergoing diverse activation response dysfunction. This article summarizes alterations astrocyte phenotypic characteristics across pathological factors It also discusses clinical value critical pathologic diagnostic marker potential therapeutic target for MetS-associated

Язык: Английский

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Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures

Translational Psychiatry, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 10, 2024

Abstract Antipsychotic (AP)-naive first-episode psychosis (FEP) patients display early dysglycemia, including insulin resistance and prediabetes. Metabolic dysregulation may therefore be intrinsic to spectrum disorders (PSDs), independent of the metabolic effects APs. However, potential biological pathways that overlap between PSDs dysglycemic states remain identified. Using meta-analytic approaches transcriptomic datasets, we investigated whether AP-naive FEP share overlapping gene expression signatures with non-psychiatrically ill dysglycemia individuals. We meta-analyzed peripheral datasets subjects identify common signatures. Common underwent pathway enrichment analysis were then used new pharmacological compounds via Integrative Library Integrated Network-Based Cellular Signatures (iLINCS). Our search results yielded 5 studies 4 which met inclusion criteria. discovered exhibiting shared 221 signatures, enriched for related endoplasmic reticulum stress abnormal brain energetics. Nine FDA-approved drugs identified as drug treatments, antidiabetic metformin, first-line treatment type 2 diabetes, has evidence attenuate dysfunction in PSDs. Taken together, our findings support changes associating disorders. These data suggest pathobiology overlaps potentially contributes dysglycemia. Finally, find metformin a

Язык: Английский

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Potential role of ghrelin in neuroprotection and cognitive function: implications for diabetic cognitive impairment

PeerJ, Год журнала: 2025, Номер 13, С. e18898 - e18898

Опубликована: Фев. 21, 2025

Ghrelin is a class of brain and intestinal peptides. It regulates food intake body glucose levels maintains cellular homeostasis. In recent years, research has revealed that ghrelin may positively impact learning memory. Despite ghrelin’s multiple functions in the central nervous system, its use as therapeutic agent for neurologic dysfunction remains unclear. Diabetic cognitive impairment (DCI) severe neurological complication diabetes mellitus. Its incidence increasing comorbidity endocrinology neurology. Additionally, it risk factor Alzheimer’ s disease (AD). are altered patients with mellitus combined impairment. Furthermore, modulation improved function rats DCI. These findings suggest potential importance pathogenesis This article presents comprehensive review DCI by mimics. this study elucidates prospects mimics DCI, aiming to identify novel targets avenues prevention management future.

Язык: Английский

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Neuroprotective Effect of Perillyl alcohol in Sporadic Alzheimer’s disease in Rats

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177558 - 177558

Опубликована: Апрель 1, 2025

Язык: Английский

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MKK3 K329 Mutation Attenuates Diabetes-Associated Cognitive Dysfunction by Blocking the MKK3-RAGE Interaction and Inhibiting Neuroinflammation

Aging and Disease, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

The receptor for advanced glycation end products (RAGE) contributes to diabetes-associated cognitive dysfunction (DACD) through the interaction of its C-terminal AAs 2-5 with mitogen-activated protein kinase 3 (MKK3). However, associated MKK3 binding site is unknown. Here, db/db mice were used as a model type 2 diabetes. GST pull-down assays and AutoDock Vina simulations conducted identify key RAGE in MKK3. This was mutated investigate effects on DACD elucidate underlying mechanisms. RAGE, levels inflammatory factors, activation microglia astrocytes tested. Synaptic morphology plasticity hippocampal neurons assessed via electrophysiological recordings Golgi staining. Behavioral tests assess function. In this study, bound directly lysine 329 (K329), leading nuclear factor-κB (NF-κB) signaling pathway, which turn triggered neuroinflammation synaptic dysfunction, ultimately contributed DACD. mutation at K329 reversed deficits by downregulating NF-κB pathway inhibiting neuroinflammation. These results confirm that hippocampus rely direct RAGE. We conclude (ct-RAGE) mechanism are induced hippocampus. study presents novel proposes therapeutic avenue neuroprotection

Язык: Английский

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Alzheimer’s Disease, Obesity, and Type 2 Diabetes: Focus on Common Neuroglial Dysfunctions (Critical Review and New Data on Human Brain and Models)

Brain Sciences, Год журнала: 2024, Номер 14(11), С. 1101 - 1101

Опубликована: Окт. 30, 2024

Obesity, type 2 diabetes (T2D), and Alzheimer's disease (AD) are pathologies that affect millions of people worldwide. They have no effective therapy difficult to prevent control when they develop. It has been known for many years these diseases pathogenic aspects in common. We highlight this review neuroglial cells (astroglia, oligodendroglia, microglia) play a vital role the origin, clinical-pathological development, course brain neurodegeneration. Moreover, we include new results T2D-AD mouse model (APP+PS1 mice on high-calorie diet) investigating.

Язык: Английский

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Insights from insulin resistance pathways: Therapeutic approaches against Alzheimer associated diabetes mellitus

Journal of Diabetes and its Complications, Год журнала: 2023, Номер 37(11), С. 108629 - 108629

Опубликована: Окт. 18, 2023

Язык: Английский

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Astaxanthin: A Marine Drug That Ameliorates Cerebrovascular-Damage-Associated Alzheimer’s Disease in a Zebrafish Model via the Inhibition of Matrix Metalloprotease-13

Marine Drugs, Год журнала: 2023, Номер 21(8), С. 433 - 433

Опубликована: Июль 31, 2023

Alzheimer's disease (AD) is a major type of dementia disorder. Common cognitive changes occur as result cerebrovascular damage (CVD) via the disruption matrix metalloproteinase-13 (MMP-13). In diabetic cases, progress vascular faster and AD rate higher. Patients with 2 diabetes are known to have higher risk factor for progression. Hence, this study designed investigate role astaxanthin (AST) in CVD-associated zebrafish inhibition MMP-13 activity. CVD was developed through intraperitoneal intracerebral injection streptozotocin (STZ). The AST (10 20 mg/L), donepezil (1 inhibitor (i.e., CL-82198; 10 μM) were exposed 21 consecutive days animals. evaluated light dark chamber tests, color recognition test, T-maze test. biomarkers pathology assessed estimation cerebral extravasation Evans blue, tissue nitrite, amyloid beta-peptide aggregation, activity, acetylcholinesterase results revealed that exposure leads ameliorative behavioral biochemical changes. can be used management due its multi-targeted actions, including inhibition.

Язык: Английский

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Structural and functional alterations of the hippocampal subfields in T2DM with mild cognitive impairment and insulin resistance: A prospective study

Journal of Diabetes, Год журнала: 2024, Номер 16(11)

Опубликована: Ноя. 1, 2024

Abstract Background Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR) and often accompanied mild cognitive impairment (MCI). The detrimental effects of T2DM IR on the hippocampus have been extensively demonstrated. Few studies examined structure function hippocampal subfields in T2DM‐MCI patients. Method A total 104 patients were recruited this prospective study divided into four groups (T2DM‐MCI‐higherIR, n = 17; T2DM‐MCI‐lowerIR, 32; T2DM‐nonMCI‐higherIR, 19; T2DM‐nonMCI‐lowerIR, 36). Structure MRI data captured. Clinical variables neuropsychological scores determined for all participants. Hippocampal subfield volume functional connectivity compared among groups. Partial correlation analysis was performed between imaging indicators, clinical variables, Results ‐ MCI higher group had smallest volumes bilateral tail, right subiculum‐body, GC ML DG ‐body, CA4 ‐body. ‐body exerted main effect. Furthermore, elevated found subiculum‐body dorsolateral prefrontal cortex anterior cingulate–medial cortex. positively correlates with cholesterol triglycerides negatively fasting insulin. Conclusion present that structural alterations subfields, a negative factor influencing alteration volume. These findings support importance might be potential neuroimaging biomarkers cerebral image

Язык: Английский

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Operational Modal Analysis of Near-Infrared Spectroscopy Measure of 2-Month Exercise Intervention Effects in Sedentary Older Adults with Diabetes and Cognitive Impairment

Brain Sciences, Год журнала: 2023, Номер 13(7), С. 1099 - 1099

Опубликована: Июль 20, 2023

The Global Burden of Disease Study (GBD 2019 Diseases and Injuries Collaborators) found that diabetes significantly increases the overall burden disease, leading to a 24.4% increase in disability-adjusted life years. Persistently high glucose levels can cause structural functional changes proteins throughout body, accumulation protein aggregates brain be associated with progression Alzheimer's (AD). To address this type 2 mellitus (T2DM), combined aerobic resistance exercise program was developed based on recommendations American College Sports Medicine. prospectively registered clinical trials (NCT04626453, NCT04812288) involved two groups: an Intervention group older sedentary adults T2DM Control healthy who could either active or sedentary. completion rate for 2-month high, participants completing average 89.14% sessions. This indicated practical, feasible, well tolerated, even during COVID-19 pandemic. It also safe, requiring minimal equipment no supervision. Our paper presents portable near-infrared spectroscopy (NIRS) measures showed muscle oxygen saturation (SmO2), i.e., balance between delivery consumption muscle, drop bilateral heel rise task (BHR) 6 min walk (6MWT) (

Язык: Английский

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