Metabolic Stress and Inflammation: Implication in Treatment for Neurological Disorders

Kumar, Ashutosh; Datusalia, Ashok Kumar

doi:10.2174/187152731709180926121555

Cited by 9 publications

(6 citation statements)

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“…Dolors Puigoriol-Illamola 1,3 , Rosana Leiva 2,4 , Manel Vázquez-Carrera 1,4,5,6 , Santiago Vázquez 2,4 , Christian Griñán-Ferré 1,3*…”

Section: β-Hsd1 Inhibition Rescues Samp8 Cognitive Impairment Induced By Metabolic Stressunclassified

“…Obesity has recently been considered to play an essential role in mild cognitive impairment (MCI) and dementia [2,3]. Abundant pieces of evidence suggest that pathological glucocorticoids (GCs) excess not only is associated with age-related cognitive decline but also with metabolic stress, obesity, and diabetes [4][5][6][7]. Thus, it has been described that prolonged exposure to increased levels of GCs exerts deleterious effects on hippocampal electrophysiology, structure and function, both in rodents [8] and humans [9], being part of altered intercellular communication, considered one of the nine hallmarks of aging [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, several hypotheses argument a link between altered glucose metabolism and dementia, considering an altered metabolic pathway as a potential contributor to persistent oxidative stress (OS) that culminates into neuronal dysfunction and dementia [22]. Increased OS, neuroinflammation, endoplasmic reticulum (ER) stress, misfolded proteins removal pathways, and autophagy, have been identified as components of neuronal metabolic stress, thus developing and aggravating neurological disorders and cognitive impairment, pointing to their implication in the dysregulated energy metabolism characteristic of ageing [23]. Thus, recent studies have focused on the pathology of cognitive decline and neurodegeneration through high-fat diet (HFD) intervention that leads to metabolic stress [24,25].…”

Section: Introductionmentioning

confidence: 99%

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11β-HSD1 Inhibition Rescues SAMP8 Cognitive Impairment Induced by Metabolic Stress

et al. 2019

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Aging and obesity have been shown to increase the risk of cognitive decline and Alzheimer's disease (AD). Besides, elevated glucocorticoids (GCs) levels cause metabolic stress and have been associated with the neurodegenerative process. Direct pieces of evidence link the reduction of GCs caused by the inhibition of 11β-HSD type 1 (11β-HSD1) with cognitive improvement.In the present study, we investigated the beneficial effects of 11β-HSD1 inhibitor (i) RL-118 after high-fat diet (HFD) treatment in the senescence-accelerated mouse prone 8 (SAMP8). We found an improvement in glucose intolerance induced by HFD in mice treated with RL-118, a significant reduction in 11β-HSD1 and glucocorticoid receptor (GR) protein levels. Furthermore, specific modifications in the FGF21 activation after treatment with 11β-HSD1i, RL-118, which induced changes in SIRT1/PGC1α/AMPKα pathway, were found. Oxidative stress (OS) and reactive oxygen species (ROS), as well as inflammatory markers and microglial activation, were significantly diminished in HFD mice treated with 11β-HSD1i. Remarkably, treatment with 11β-HSD1i altered PERK pathway in both diet groups, increasing autophagy only in HFD mice group.After RL-118 treatment, a decrease in glycogen synthase kinase 3 (GSK3β) activation, Tau hyperphosphorylation, BACE1 protein levels and the product β-CTF were found. Increases in the non-amyloidogenic secretase ADAM10 protein levels and the product sAPPα were found in both treated mice, regardless of the diet. Consequently, beneficial effects on social behaviour and cognitive performance were found in treated mice. Thus, our results support the therapeutic strategy of selective 11β-HSD1i for the treatment of age-related cognitive decline and AD.

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“…Dolors Puigoriol-Illamola 1,3 , Rosana Leiva 2,4 , Manel Vázquez-Carrera 1,4,5,6 , Santiago Vázquez 2,4 , Christian Griñán-Ferré 1,3*…”

Section: β-Hsd1 Inhibition Rescues Samp8 Cognitive Impairment Induced By Metabolic Stressunclassified

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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11β-HSD1 Inhibition Rescues SAMP8 Cognitive Impairment Induced by Metabolic Stress

et al. 2019

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“…To date, the understanding of the underlying molecular mechanisms of some metabolic or neurological diseases and the deepening of knowledge on the role of inflammation in these disorders have radically changed our understanding of their etiology [1,2]. Alzheimer's (AD) and Parkinson's disease, type 1 and type 2 diabetes, and obesity are just some of the pathologies for which a well-defined role of inflammation has been identified, with consequent possible therapeutic implications [3,4]. For example, activated astrocytes and microglia are characteristically found in abundance near neurons and plaques in AD [5] and the block of the activation of insulin signaling receptors caused by the chronic exposure of pro-inflammatory mediators in β-cells of pancreatic islets has been evidenced in the pathogenesis of insulin resistance which underlies many metabolic diseases [6,7].…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Biomarkers are Correlated with Some Forms of Regressive Autism Spectrum Disorder

et al. 2019

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Background: Several studies have tried to investigate the role of inflammatory biomarkers in Autism Spectrum Disorder (ASD), and their correlations with clinical phenotypes. Despite the growing research in this topic, existing data are mostly contradictory. Methods: Eighty-five ASD preschoolers were assessed for developmental level, adaptive functioning, gastrointestinal (GI), socio-communicative and psychopathological symptoms. Plasma levels of leptin, resistin, plasminogen activator inhibitor-1 (PAI-1), macrophage chemoattractant protein-1 (CCL2), tumor necrosis factor-alfa (TNF-α), and interleukin-6 (IL-6) were correlated with clinical scores and were compared among different ASD subgroups according to the presence or absence of: (i) GI symptoms, (ii) regressive onset of autism. Results: Proinflammatory cytokines (TNF-α, IL-6 and CCL2) were lower than those reported in previous studies in children with systemic inflammatory conditions. GI symptoms were not correlated with levels of inflammatory biomarkers except for resistin that was lower in ASD-GI children (p = 0.032). Resistin and PAI-1 levels were significantly higher in the group with “regression plus a developmental delay” onset (Reg+DD group) compared to groups without regression or with regression without a developmental delay (p < 0.01 for all). Conclusions: Our results did not highlight the presence of any systemic inflammatory state in ASD subjects neither disentangling children with/without GI symptoms. The Reg + DD group significantly differed from others in some plasmatic values, but these differences failed to discriminate the subgroups as possible distinct ASD endo-phenotypes.

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“…Previous studies have shown that the consumption of a high-cholesterol and/or HFD is associated with an increase in the prevalence of vascular diseases [8][9][10]. Hypercholesterolemia is one of the most important risk factors for cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

Effect of dyslipidemia on vascular smooth muscle cell proliferation in a porcine coronary restenosis model

Jeong¹,

Kang²,

Lee³

et al. 2019

J Biomed Transl Res

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This study aimed to examine the effect of a mild elevation in serum cholesterol level in a porcine coronary overstretch restenosis model using a balloon angioplasty catheter or drug-eluting coronary stent. Pigs were divided into two groups and were fed a commercial normal diet (CND, n = 4) or a high-fat diet (HFD, n = 4) for 5 weeks. Coronary overstretch injury by balloon angioplasty or stent implantation was induced in the left anterior descending and left circumflex artery after 1 week of feeding. Histopathological analysis was performed at 4 weeks after coronary injury. During the experiment, the total cholesterol level in the HFD group increased by approximately 44.9% (from 65.9 ± 3.21 mg/dL at baseline to 95.5 ± 9.94 mg/dL at 5 weeks). The lumen area in the CND group was reduced in comparison with that in the HFD group after balloon angioplasty. After stent implantation, the injury score showed no significant difference. There were significant differences in the neointimal area (2.7 ± 0.33 mm 2 in the CND group vs. 3.3 ± 0.34 mm 2 in the HFD group, p<0.05), lumen area (2.6 ± 0.54 mm 2 in the CND group vs. 2.0 ± 0.33 mm 2 in the HFD group, p<0.05), and percent area stenosis (52.0 ± 7.96% in the CND group vs. 62.4 ± 5.15% in the HFD group, p<0.05). Body weight change was not different between the two groups.Increased serum cholesterol level activated vascular smooth muscle cell proliferation in the porcine coronary overstretch model.

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Metabolic Stress and Inflammation: Implication in Treatment for Neurological Disorders

Cited by 9 publications

References 0 publications

11β-HSD1 Inhibition Rescues SAMP8 Cognitive Impairment Induced by Metabolic Stress

11β-HSD1 Inhibition Rescues SAMP8 Cognitive Impairment Induced by Metabolic Stress

Inflammatory Biomarkers are Correlated with Some Forms of Regressive Autism Spectrum Disorder

Effect of dyslipidemia on vascular smooth muscle cell proliferation in a porcine coronary restenosis model

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