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https://www.readbyqxmd.com/read/29782959/targeting-central-%C3%AE-2-receptors-ameliorates-streptozotocin-induced-neuroinflammation-via-inhibition-of-glycogen-synthase-kinase3-pathway-in-mice
#1
Nora O Abdel Rasheed, Nesrine S El-Sayed, Aiman S El-Khatib
Alzheimer's disease (AD) is portrayed by progressive cognitive decline and pathological deposition of amyloid plaques as well as neurofibrillary tangles. Most of AD cases are sporadic, resulting from overlap of various environmental and genetic factors. Intra-cerebroventricular injection of streptozotocin (STZ) leads to insulin resistance brain state accompanied by memory decline, oxidative stress, and neuro-degeneration which mimic the pathologies associated with sporadic Alzheimer's disease (SAD). In the current study, protective effects of formoterol in STZ-induced SAD were studied...
May 18, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29778668/thinking-about-brain-insulin-resistance
#2
REVIEW
Reem M Al Haj Ahmad, Hayder A Al-Domi
INTRODUCTION: Dementia and type 2 diabetes mellitus (T2DM) are two of the epidemics of our time; in which insulin resistance (IR) is playing the central role. Epidemiological studies found that different types of dementia development may be promoted by the presence of T2DM. OBJECTIVES: We aimed in this review to highlight the role of insulin and the IR in the brain as a pathophysiological factor of dementia development and also to expand our understanding of T2DM as a mediator of IR in the brain and to review the possible mechanisms of action that may explain the association...
May 6, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29773001/combined-administration-of-monosodium-glutamate-and-high-sucrose-diet-accelerates-the-induction-of-type-2-diabetes-vascular-dysfunction-and-memory-impairment-in-rats
#3
Kaja Saikrishna, Ringu Kumari, Kantamaneni Chaitanya, Subhankar Biswas, Pawan G Nayak, Jayesh Mudgal, Anoop Kishore, Krishnadas Nandakumar
In this study, we aimed to develop an experimental animal model for type 2 diabetes mellitus (T2DM) using a combination of monosodium glutamate (MSG) and high sucrose diet (HSD). Young male Wistar rats (20-30 g) were injected with MSG (2 or 4 mg/g, i.p. for 4 days). These rats were also fed an HSD, while the control group was fed a starch diet (SFD) for 150 days. Parameters assessed periodically were body weight, feed intake, blood glucose level, and oral glucose tolerance test (OGTT), lipid profile, liver and kidney function tests, skeletal muscle glucose uptake, cognitive function tests, and microvascular changes using isolated rat aorta...
2018: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29748034/ampk-induced-memory-improvements-in-the-diabetic-population-a-case-study
#4
Alicia Halikas, Kelly J Gibas
Diabetics in mid-life carry a 1.5 times higher risk of developing Alzheimer's disease than those diagnosed with diabetes (T2D) later in life [1]. Recent research points to accelerated cognitive decline within a range of 20%-50% for middle-aged diabetics as compared to non-diabetic populations [2,3]. Metabolic syndrome (MetS), a type 2 diabetes (T2D) precursor, is also linked to MCI and AD pathologies via hypo-metabolic brain circuitry that inhibits glucose metabolism and attenuates cognitive function [4]. Dysregulation of intracellular and extracellular signaling as mediated by the mTOR and AMPK pathways is the result...
April 27, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29743868/insulin-resistance-as-a-therapeutic-target-in-the-treatment-of-alzheimer-s-disease-a-state-of-the-art-review
#5
REVIEW
Christian Benedict, Claudia A Grillo
Research in animals and humans has shown that type 2 diabetes and its prodromal state, insulin resistance, promote major pathological hallmarks of Alzheimer's disease (AD), such as the formation of amyloid plaques and neurofibrillary tangles (NFT). Worrisomely, dysregulated amyloid beta (Aβ) metabolism has also been shown to promote central nervous system insulin resistance; although the role of tau metabolism remains controversial. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted insulin signaling...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29740969/peripheral-cannabinoid-1-receptor-blockade-mitigates-adipose-tissue-inflammation-via-nlrp3-inflammasome-in-mouse-models-of-obesity
#6
Ji Hye Han, Hanho Shin, Jun Gi Rho, Jung-Eun Kim, Dong Hwee Son, Juhwan Yoon, Yong Jae Lee, Jung-Hyuck Park, Byung Jeong Song, Chang-Sik Choi, Seul Gi Yoon, Il Yong Kim, Eun Kyung Lee, Je Kyung Seong, Ki Woo Kim, Wook Kim
AIMS: Cannabinoid 1 receptor (CB1R) antagonists have been shown to improve insulin resistance and the associated metabolic abnormalities, but their therapeutic development was discontinued due to neuropsychiatric side effects. This study evaluated AJ5018 as the peripherally restricted CB1R antagonist, synthesized by modifying the structure of its brain-penetrant parent compound rimonabant, and analyzed the metabolic parameters and adipose tissue inflammation via NLRP3 inflammasome following chronic treatment of mouse models of obesity with AJ5018...
May 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29740395/maternal-diet-metabolic-state-and-inflammatory-response-exert-unique-and-long-lasting-influences-on-offspring-behavior-in-non-human-primates
#7
Jacqueline R Thompson, Hanna C Gustafsson, Madison DeCapo, Diana L Takahashi, Jennifer L Bagley, Tyler A Dean, Paul Kievit, Damien A Fair, Elinor L Sullivan
Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes) increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD), metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29738527/defensive-effect-of-microrna-200b-c-against-amyloid-beta-peptide-induced-toxicity-in-alzheimer-s-disease-models
#8
Sayuri Higaki, Masashi Muramatsu, Akio Matsuda, Kenji Matsumoto, Jun-Ichi Satoh, Makoto Michikawa, Shumpei Niida
MiRNA molecules are important post-transcriptional regulators of gene expression in the brain function. Altered miRNA profiles could represent a defensive response against the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD). Endogenous miRNAs have lower toxic effects than other gene silencing methods, thus enhancing the expression of defensive miRNA could be an effective therapy. However, little is known about the potential of targeting miRNAs for the treatment of AD. Here, we examined the function of the miR-200 family (miR-200a, -141, -429, -200b, -200c), identified using miRNA microarray analysis of cortical tissue from Tg2576 transgenic mice...
2018: PloS One
https://www.readbyqxmd.com/read/29736736/the-medial-septum-is-insulin-resistant-in-the-ad-presymptomatic-phase-rescue-by-nerve-growth-factor-driven-irs-1-activation
#9
Valentina Sposato, Nadia Canu, Elena Fico, Salvatore Fusco, Giulia Bolasco, Maria Teresa Ciotti, Matteo Spinelli, Delio Mercanti, Claudio Grassi, Viviana Triaca, Pietro Calissano
Basal forebrain cholinergic neurons (BFCN) are key modulators of learning and memory and are high energy-demanding neurons. Impaired neuronal metabolism and reduced insulin signaling, known as insulin resistance, has been reported in the early phase of Alzheimer's disease (AD), which has been suggested to be "Type 3 Diabetes." We hypothesized that BFCN may develop insulin resistance and their consequent failure represents one of the earliest event in AD. We found that a condition reminiscent of insulin resistance occurs in the medial septum of 3 months old 3×Tg-AD mice, reported to develop typical AD histopathology and cognitive deficits in adulthood...
May 7, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29731703/metabolic-syndrome-and-neuroprotection
#10
REVIEW
Melisa Etchegoyen, Mariana H Nobile, Francisco Baez, Barbara Posesorski, Julian González, Néstor Lago, José Milei, Matilde Otero-Losada
Introduction: Over the years the prevalence of metabolic syndrome (MetS) has drastically increased in developing countries as a major byproduct of industrialization. Many factors, such as the consumption of high-calorie diets and a sedentary lifestyle, bolster the spread of this disorder. Undoubtedly, the massive and still increasing incidence of MetS places this epidemic as an important public health issue. Hereon we revisit another outlook of MetS beyond its classical association with cardiovascular disease (CVD) and Diabetes Mellitus Type 2 (DM2), for MetS also poses a risk factor for the nervous tissue and threatens neuronal function...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29721854/abscisic-acid-supplementation-rescues-high-fat-diet-induced-alterations-in-hippocampal-inflammation-and-irss-expression
#11
Alberto Ribes-Navarro, Mariam Atef, Sandra Sánchez-Sarasúa, María Teresa Beltrán-Bretones, Francisco Olucha-Bordonau, Ana María Sánchez-Pérez
Accumulated evidence indicates that neuroinflammation induces insulin resistance in the brain. Moreover, both processes are intimately linked to neurodegenerative disorders, including Alzheimer's disease. Potential mechanisms underlying insulin resistance include serine phosphorylation of the insulin receptor substrate (IRS) or insulin receptor (IR) misallocation. However, only a few studies have focused on IRS expression in the brain and its modulation in neuroinflammatory processes. This study used the high-fat diet (HFD) model of neuroinflammation to study the alterations of IR, an insulin-like growth factor receptor (IGF1R) and IRS expressions in the hippocampus...
May 2, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29712510/modulation-of-brain-insulin-signaling-in-alzheimer-s-disease-new-insight-on-the-protective-role-of-green-coffee-bean-extract
#12
Hoda E Mohamed, Mervat E Asker, Nahla N Younis, Mohamed A Shaheen, Rana G Eissa
OBJECTIVE: Alzheimer's disease (AD), a neurodegenerative disorder, involves brain insulin signaling cascades and insulin resistance (IR). Because of limited treatment options, new treatment strategies are mandatory. Green coffee bean extract (GCBE) was reported to attenuate IR and improve brain energy metabolism. We aimed to investigate the possible use of GCBE as a prophylactic strategy to delay the onset of AD or combined with pioglitazone (PIO) as a strategy to retard the progression of AD...
May 1, 2018: Nutritional Neuroscience
https://www.readbyqxmd.com/read/29710715/targeting-insulin-for-alzheimer-s-disease-mechanisms-status-and-potential-directions
#13
Jung Hyun Lee, Jordan B Jahrling, Larry Denner, Kelly T Dineley
Insulin resistance can occur when the body is unable to respond to insulin even in excess. In the brain, insulin manages glucose metabolism in regions such as the hippocampus and plays a key role in directly regulating ERK, a kinase required for the type of memory compromised in early Alzheimer's disease (AD). Human imaging studies show that brain glucose utilization declines with age and is notably impaired in subjects with early AD. Likewise, animal models of AD or insulin resistance, or both, demonstrate that dysfunctional insulin signaling and insulin resistance in the brain have reciprocity with neuroinflammation and aberrant accumulation of amyloid-β (Aβ), pathological hallmarks in AD...
April 27, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29706312/metabolic-syndrome-marks-early-risk-for-cognitive-decline-with-apoe4-gene-variation-a-case-study
#14
Dawson Brown, Kelly J Gibas
A vast amount of research has been done on the APOE4 genetic marker for Alzheimer's disease (AD), but its connection to metabolic processes associated with peripheral insulin resistance and cerebral glucose metabolism is still relatively unknown. The APOE4 allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, particularly in individuals who have inherited two copies of the gene (Zhao et al., 2017). In this case study, a 38 year old male with metabolic syndrome (MetS), the APOE4 gene, early stage memory problems and a family history of Alzheimer's Disease (AD) was placed on a ketogenic diet combined with high intensity interval training (HIIT) for 10 weeks...
April 20, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29701665/adropin-contributes-to-anti-atherosclerosis-by-suppressing-monocyte-endothelial-cell-adhesion-and-smooth-muscle-cell-proliferation
#15
Kengo Sato, Tomoyuki Yamashita, Remina Shirai, Koichiro Shibata, Taisuke Okano, Maho Yamaguchi, Yusaku Mori, Tsutomu Hirano, Takuya Watanabe
Adropin, a peptide hormone expressed in liver and brain, is known to improve insulin resistance and endothelial dysfunction. Serum levels of adropin are negatively associated with the severity of coronary artery disease. However, it remains unknown whether adropin could modulate atherogenesis. We assessed the effects of adropin on inflammatory molecule expression and human THP1 monocyte adhesion in human umbilical vein endothelial cells (HUVECs), foam cell formation in THP1 monocyte-derived macrophages, and the migration and proliferation of human aortic smooth muscle cells (HASMCs) in vitro and atherogenesis in Apoe -/- mice in vivo...
April 26, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29698389/importance-of-integrating-nanotechnology-with-pharmacology-and-physiology-for-innovative-drug-delivery-and-therapy-an-illustration-with-firsthand-examples
#16
REVIEW
Rui Xue Zhang, Jason Li, Tian Zhang, Mohammad A Amini, Chunsheng He, Brian Lu, Taksim Ahmed, HoYin Lip, Andrew M Rauth, Xiao Yu Wu
Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies...
May 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29696164/the-design-and-rationale-of-the-beijing-vascular-disease-patients-evaluation-study-best-study
#17
Huan Liu, Jinbo Liu, Hongwei Zhao, Lihong Li, Guangyun Shang, Yingyan Zhou, Hongyu Wang
Aims: Arteriosclerosis and arterial stiffness increasing are the basic pathophysiological changes of vascular-related diseases, and also the predictor factors of future cardiovascular events. Plasma biomarkers such as glucose, lipids, Homocysteine (Hcy), N-terminal pro-brain natriuretic peptide (NT-proBNP) have been shown to be involved the development of arteriosclerosis. The present study is a prospective observational and follow-up study of the characteristics of subclinical vascular disease detected by non-invasive methods that can predict progression of clinical overt vascular events in a Chinese population...
September 2017: Contemporary Clinical Trials Communications
https://www.readbyqxmd.com/read/29687902/impact-of-metabolic-diseases-on-cerebral-circulation-structural-and-functional-consequences
#18
Maha Coucha, Mohammed Abdelsaid, Rebecca Ward, Yasir Abdul, Adviye Ergul
Metabolic diseases including obesity, insulin resistance, and diabetes have profound effects on cerebral circulation. These diseases not only affect the architecture of cerebral blood arteries causing adverse remodeling, pathological neovascularization, and vasoregression but also alter the physiology of blood vessels resulting in compromised myogenic reactivity, neurovascular uncoupling, and endothelial dysfunction. Coupled with the disruption of blood brain barrier (BBB) integrity, changes in blood flow and microbleeds into the brain rapidly occur...
March 25, 2018: Comprehensive Physiology
https://www.readbyqxmd.com/read/29678606/ketogenic-diet-high-intensity-interval-training-hiit-and-memory-training-in-the-treatment-of-mild-cognitive-impairment-a-case-study
#19
Kaitlyn Dahlgren, Kelly J Gibas
Alzheimer's disease (AD) deaths have increased by 89% since 2000. This alarming trajectory of neurological disease highlights the failure of current best practice. Deteriorating brain fuel supply is the nemesis of intact neurological health. Cerebral hypo-metabolism associated with AD occurs years before onset. Both the ketogenic diet and calorie restriction (fasting) lead to a compensatory rise in ketones to improve energy deficits in the brain derived from cerebral insulin resistance. Two forms of ketone bodies, β-hydroxybutyrate and acetoacetate, fuel the brain during starvation, fasting and strenuous exercise...
April 11, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29678475/both-oophorectomy-and-obesity-impaired-solely-hippocampal-dependent-memory-via-increased-hippocampal-dysfunction
#20
Duangkamol Mantor, Wasana Pratchayasakul, Wanitchaya Minta, Wissuta Sutham, Siripong Palee, Jirapas Sripetchwandee, Sasiwan Kerdphoo, Thidarat Jaiwongkum, Sirawit Sriwichaiin, Warunsorn Krintratun, Nipon Chattipakorn, Siriporn C Chattipakorn
Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats...
April 17, 2018: Experimental Gerontology
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