Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants

Nature Medicine, Journal Year: 2016, Volume and Issue: 22(3), P. 238 - 249

Published: March 1, 2016

Language: Английский

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The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson's disease: mechanisms of action

Drug Discovery Today, Journal Year: 2016, Volume and Issue: 21(5), P. 802 - 818

Published: Feb. 3, 2016

Growing evidence suggests that agonists of the glucagon-like peptide 1 (GLP-1) receptor provide neuroprotection across a range experimental models Parkinson's disease (PD) and, recently, small proof-of-concept, open-label human trial exenatide in treatment moderate severity PD appeared to show persistent improvements motor and cognitive function. The underlying mechanisms action remain unclear, but as for potential use GLP-1 treating several neurodegenerative mounts, with clinical trials analogues Alzheimer's (AD) currently underway, here we review molecular neuroprotective effects laboratory their therapeutic utility particular relevance dementia (PDD).

Language: Английский

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Insulin resistance and Parkinson’s disease: A new target for disease modification?

Progress in Neurobiology, Journal Year: 2016, Volume and Issue: 145-146, P. 98 - 120

Published: Oct. 1, 2016

Language: Английский

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The menace of obesity to depression and anxiety prevalence

Trends in Endocrinology and Metabolism, Journal Year: 2021, Volume and Issue: 33(1), P. 18 - 35

Published: Nov. 5, 2021

Obesity increases the incidence of depression and anxiety as a function extent metabolic dysfunction.Diets that include excess saturated fat sugar intake promote dysfunction, neuroinflammation, mental health impairments.Adipose- gut-derived inflammation changes in brain nutrient composition stimulate neuroinflammation.Neuroinflammation alters structure, excitability, connectivity corticolimbic networks controlling mood, motivation, emotion. The is amplified by obesity. Mounting evidence reveals psychiatric consequences obesity stem from poor diet, inactivity, visceral adipose accumulation. Resulting vascular including inflammation, insulin leptin resistance, hypertension, have emerged key risks to development. Recent research advancements are exposing important contribution these different corollaries their impact on neuroimmune status neural circuits mood emotional states. Along lines, this review connects clinical manifestations our current understanding origins biology immunometabolic threats central nervous system behavior. peril disorders receiving increasing attention beyond psychological practice, an expansion encouraging constructive awareness discussion public forums. centrality overall wellbeing substantial external stressors has never been more apparent. major influence internal, biological originating alterations energy metabolism also earned significant consideration. In keeping with its extensive physiology health, growing accentuating threat risk illness. Depression prevalent disabling conditions increased hazard they pose for obese individuals far-reaching. Beyond hindering personal welfare quality life, depressed can diminish will seek out adhere therapeutic interventions. interchange between dysfunction perpetuate cycle despair, overeating physical inactivity enhances severity numerous associated risks. view limitations available therapies, it critical improve knowledge dietary, metabolic, neurobiological effectors development progression implement better preventative treatment strategies. An elevated body mass index (BMI) predictive chronic course depressive symptoms [1.Zhao G. et al.Depression among US adults: associations index.Int. J. Obes. 2009; 33: 257-266Crossref PubMed Scopus (161) Google Scholar,2.Milaneschi Y. obesity: shared mechanisms.Mol. Psychiatry. 2019; 24: 18-33Crossref (157) Scholar]. odds developing disorder (MDD) increase number coexisting impairments, such those characteristic syndrome [3.Jokela M. al.Association metabolically healthy symptoms: pooled analysis eight studies.Mol. 2014; 19: 910-914Crossref (60) Scholar,4.Tang F. syndrome: systematic meta-analysis epidemiological studies.Psychoneuroendocrinology. 2017; 77: 112-121Crossref (0) coupled various structural functional remarkably similar observed disorders, region-specific cell density compromised excitability [5.Rapuano K.M. al.Nucleus accumbens cytoarchitecture predicts weight gain children.Proc. Natl. Acad. Sci. U. S. A. 2020; 117: 26977-26984Crossref (8) Scholar,6.Opel N. al.Brain abnormalities relation age, genetic risk, common disorders: through univariate multivariate mega-analysis 6420 participants ENIGMA MDD working group.Mol. 2021; 26: 4839-4852Crossref (15) Several lines suggest prolonged caused dietary lifestyle resulting required outcomes. Clinical observations combined rodent models exhibiting depressive- anxiety-like behaviors proving valuable uncovering mechanisms involved. review, we focus how (for cognitive corollaries, see [7.Farruggia M.C. Small D.M. Effects adiposity cognition: review.Physiol. Behav. 208: 112578Crossref (25) Scholar,8.Kendig M.D. al.Unravelling impacts western-style diets brain, gut microbiota cognition.Neurosci. Biobehav. Rev. 128: 233-243Crossref Scholar]), aim illuminate diverse culprits behavioral processes giving rise deficits. (or depression) debilitating condition genetic, epigenetic, environmental contributions. manifest ways, modulating homeostatic functions appetite sleep turn further alter mood. Anxiety accompanies most cases indicative poorer prognosis. Melancholic depression, form, distinguished hypophagia, hyposomnia, anhedonia (decreased capacity experience anticipate pleasure). addition anhedonia, characteristics atypical subtype hyperphagia, lethargy, hypersomnia. Obese individuals, particularly presenting attributes (abdominal obesity, hyperglycemia, triglycerides), tend develop [9.Milaneschi al.Genetic association features obesity-related dysregulations.JAMA 74: 1214-1225Crossref (90) Scholar] (Box 1). This form stronger links peripheral [10.Rudolf al.Elevated IL-6 levels patients but not typical depression.Psychiatry Res. 217: 34-38Crossref (31) Scholar,11.Yoon H.K. al.Role cytokines depression.Nord. 2012; 66: 183-188Crossref [12.Woelfer al.The role subtypes within neuroinflammation hypothesis disorder.Neuroscience. 403: 93-110Crossref (46) inflammation. Individuals often unrelenting [13.Thase M.E. Recognition diagnosis depression.J. Clin. 2007; 68: 11-16Crossref Scholar], part because show response antidepressants [14.Henkel V. al.Treatment features: meta-analytic approach.Psychiatry 2006; 141: 89-101Crossref As gain, be intensified antidepressant treatments encourage vicious disease progression.Box 1Sex, gender, risksThe frequency diagnoses approximately double women compared men Scholar,157.Scott al.Age patterns prevalence DSM-IV depressive/anxiety without co-morbidity.Psychol. Med. 2008; 38: 1659-1669Crossref divergence corresponds lifetime independent weight. sex distinction narrows considerably severe (BMI ≥ 40) While differences well characterized, only recently dissimilar underlying emerging [158.Bangasser D.A. Cuarenta Sex depression: mechanisms.Nat. Neurosci. 22: 674-684Crossref Scholar]). Adiposity serves predictor than [149.Ul-Haq Z. al.Gender probable cross-sectional study 140,564 UK Biobank participants.BMC 14: 153Crossref (16) Women likely male counterparts [150.Kokras Dalla C. Preclinical response: implications research.J. 95: 731-736Crossref outcome effects stress palatable food [119.Dallman M.F. Stress-induced system.Trends Endocrinol. Metab. 2010; 21: 159-165Abstract Full Text PDF (479) both sexes, negative state robustly impairments resistance rather itself Correspondingly, nearly twice high people type 2 diabetes [159.Wang al.Prevalence comorbid diabetes: comparative studies.Diabet. 36: 961-969Crossref (19) threefold higher 1 without, greater rates diabetic [160.Roy T. Lloyd C.E. Epidemiology review.J. Affect. Disord. 142: S8-S21Crossref (538) Diabetes 48% likelihood 20% [20.Gariepy longitudinal results 12-year National Population Health Survey.Obesity (Silver Spring). 18: 1033-1038Crossref (48) consistent manner, characterized (normal blood pressure, C-reactive protein, triglycerides, glycaemia) present either no [161.Hamer al.Risk future who healthy: English ageing.Mol. 17: 940-945Crossref (81) or modest nonobese controls. However, stigmatization self-image may still contribute states problem evident women. link established. There bidirectional being overweight 25–29.99) women, relationship 30) [15.Luppino F.S. al.Overweight, studies.Arch. Gen. 67: 220-229Crossref (2217) A overview illustrates adults self-reporting 23–36% controls, whereas clinically diagnosed 14–34% [2.Milaneschi when evaluating waist-to-hip ratio [16.Zhao al.Waist circumference, abdominal U.S. Nutrition Examination Survey 2005-2006.BMC 2011; 11: 130Crossref Scholar,17.Xu Q. general population: meta-analysis.Obes. Pract. 5: e267-e360Crossref which provides estimate BMI [18.Ross R. circumference vital sign practice: consensus statement IAS ICCR Working Group Visceral Obesity.Nat. 16: 177-189Crossref (167) Emphasizing importance early detection treatment, suggests adolescents 40% [19.Mannan al.Prospective adolescent males females- studies.PLoS One. 2016; 11e0157240Crossref (37) positive anxiety: heightens (e.g., dread, unease) 30% 40%, respectively Scholar,20.Gariepy other variables moderate anxiety, degree presence cardiometabolic comorbidities, anxiety. Indeed, there 35) Contemporary environments offer abundance processed foods very tasty abnormally energy-dense, convey gustatory information learned caloric value then fall short post-ingestion noncaloric sweeteners). Sensory cues remind us affective bombard about proximity comparatively low effort cost obtain. These relatively recent world perilously intersect feeding, components favor emotion reduction facilitate encoding memories related access make feel contexts. Residing midbrain circuits, highly recruited modern environment posited largely responsible disease. symptomology [21.Wang al.Dietary inflammatory meta-analysis.Public Nutr. 2018; 1-7Google Scholar,22.Chen G.Q. health: dose-response meta-analysis.Front. 8: 662357Crossref Dietary fats endocrine, according lipid class. Prolonged interfere homeostasis stimulating deposition humans [23.Rosqvist al.Overfeeding polyunsaturated causes distinct liver accumulation humans.Diabetes. 63: 2356-2368Crossref (206) impairing signaling rodents [24.Benoit S.C. al.Palmitic acid mediates hypothalamic altering PKC-theta subcellular localization rodents.J. Invest. 119: 2577-2589Crossref (239) Scholar,25.Kleinridders al.MyD88 CNS fatty acid-induced diet-induced obesity.Cell 10: 249-259Abstract (346) Consumption [26.Lai J.S. al.Inflammation older women.Nutr. 234-245Crossref plasma concentrations palmitate [27.Tsuboi H. al.Associations serum proportions palmitic arachidonic acids, alpha-tocopherol population--a preliminary study.Clin. 2013; 32: 289-293Abstract positively correlate acute phase reactant protein (CRP) humans. causal (DIO) human studies indirect. To end, revealed high-fat diet (HFD) elicits anxiety- depressive-like [28.Sharma Fulton Diet-induced promotes behaviour adaptations reward circuitry.Int. 37: 382-389Crossref (242) Scholar, 29.Andre al.Diet-induced progressively cognition, behavior lipopolysaccharide-induced behavior: indoleamine 2,3-dioxygenase activation.Brain Immun. 41: 10-21Crossref (69) 30.da Costa Estrela D. al.Predictive female Wistar rats subjected cafeteria stress.Physiol. 2015; 151: 252-263Crossref (9) 31.Sivanathan al.Chronic feeding reduces transcript glucocorticoid signalling genes hippocampus rats.Behav. Brain 286: 265-270Crossref 32.Dutheil al.High-fat induced anhedonia: inflammation.Neuropsychopharmacology. 1874-1887Crossref (33) 33.Zemdegs impairs 5-HT mice.Br. Pharmacol. 173: 2095-2110Crossref (63) 34.Decarie-Spain L. anxiodepressive compulsive sucrose seeking elicited fat.Mol. 1-13Crossref 35.Zemdegs al.Metformin anxiolytic antidepressant-like responses insulin-resistant mice decreasing circulating branched-chain amino acids.J. 39: 5935-5948Crossref 36.Nakajima al.Saturated principal cause lysophosphatidyl choline level.Int. 44: 727-738Crossref (7) hypothalamic–pituitary–adrenal (HPA) [37.Sharma Adaptations circuitry underlie cravings withdrawal.Int. 1183-1191Crossref (135) Scholar,38.Hryhorczuk hypothalamus-pituitary-adrenal axis behaviour.Psychoneuroendocrinology. 83: 142-149Crossref triggers neurobehavioral deficits blunted mesolimbic dopamine [39.Davis J.F. al.Exposure attenuates psychostimulant turnover rat.Behav. 122: 1257-1263Crossref (234) 40.Sartorius al.Monounsaturated acids prevent aversive locomotion, activity, behavior.Diabetes. 61: 1669-1679Crossref (34) 41.Hryhorczuk al.Dampened monounsaturated lipids.Neuropsychopharmacology. 811-821Crossref (64) outcomes appear immune-stimulating properties propagate disturbances enhance neuroinflammation. Numerous findings point benefits Mediterranean-like rich unsaturated fats. Oleate, enriched olive oil, glycemic control profiles protect against [34.Decarie-Spain Scholar,42.Soriguer al.Olive oil beneficial effect impaired glucose regulation factors. [email protected] study.Eur. 911-916Crossref Omega-3 (n-3) (PUFA), docosahexaenoic (DHA) eicosapentaenoic (EPA), well-known anti-inflammatory actions. Increased n-3 sensitivity [43.Gao al.Fish supplementation sensitivity: meta-analysis.Lipids Dis. 131Crossref significantly CRP, interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα) [44.Li K. al.Effect marine-derived interleukin 6 alpha: meta-analysis.PLoS 9e88103Crossref (138) reports consumption lower [45.Grosso PUFA, fish observational studies.J. 205: 269-281Crossref demonstrate dampens indices [46.Zemdegs al.Anxiolytic- oil-enriched brain-derived neurotrophic deficient mice.Front. 12: 974Crossref Scholar,47.Laye al.Anti-inflammatory omega-3 brain: physiological relevance pharmacology.Pharmacol. 70: 12-38Crossref (150) contrast, PUFA

Language: Английский

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Therapies for Prevention and Treatment of Alzheimer’s Disease

BioMed Research International, Journal Year: 2016, Volume and Issue: 2016, P. 1 - 17

Published: Jan. 1, 2016

Alzheimer’s disease (AD) is the most common cause of dementia associated with a progressive neurodegenerative disorder, prevalence 44 million people throughout world in 2015, and this figure estimated to double by 2050. This characterized blood-brain barrier disruption, oxidative stress, mitochondrial impairment, neuroinflammation, hypometabolism; it related amyloid- β peptide accumulation tau hyperphosphorylation as well decrease acetylcholine levels reduction cerebral blood flow. Obesity major risk factor for AD, because induces adipokine dysregulation, which consists release proinflammatory adipokines decreased anti-inflammatory adipokines, among other processes. The pharmacological treatments AD can be divided into two categories: symptomatic such acetylcholinesterase inhibitors N-methyl-D-aspartate (NMDA) receptor antagonists etiology-based secretase inhibitors, amyloid binders, therapies. Strategies prevention through nonpharmacological are lifestyle interventions exercise, mental challenges, socialization caloric restriction healthy diet. an important health issue on all should informed so that strategies minimize its development may implemented.

Language: Английский

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Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease

JAMA Neurology, Journal Year: 2019, Volume and Issue: 76(4), P. 420 - 420

Published: Jan. 14, 2019

Importance

Exenatide, a glucagon-like peptide 1 agonist used in type 2 diabetes, was recently found to have beneficial effects on motor function randomized, placebo-controlled trial Parkinson disease (PD). Accumulating evidence suggests that impaired brain insulin and protein kinase B (Akt) signaling play role PD pathogenesis; however, exploring the extent which drugs engage with putative mechnisms vivo remains challenge.

Objective

To assess whether participants Exenatide-PD augmented activity Akt pathways.

Design, Setting, Participants

Serum samples were collected from 60 single-center (June 18, 2014, June 16, 2016), compared patients moderate randomized mg of exenatide once weekly or placebo for 48 weeks followed by 12-week washout period. extracellular vesicles, including exosomes, extracted, precipitated, enriched neuronal source anti–L1 cell adhesion molecule antibody absorption, proteins interest evaluated using electrochemiluminescence assays. Statistical analysis performed May 1, 2017, August 31, 2017.

Main Outcomes Measures

The main outcome manifested as change tyrosine phosphorylated receptor substrate within vesicles at end treatment. Additional measures changes other expression mitogen-activated

Results

Sixty (mean [SD] age, 59.9 [8.4] years; 43 [72%] male) participated study: 31 group 29 (data patient excluded). Patients treated had phosphorylation (0.27 absorbance units [AU]; 95% CI, 0.09-0.44 AU;P = .003) (0.23 AU; 0.05-0.41 .01) receiving placebo. Exenatide-treated elevated downstream substrates, total (0.35 U/mL; 0.16-0.53 U/mL;P < .001) mechanistic target rapamycin (mTOR) (0.22 0.04-0.40 .02). Improvements Movement Disorders Society Unified Parkinson's Disease Rating Scale part 3 off-medication scores associated levels mTOR (F_4,50 5.343,P 4.384,P .04).

Conclusions Relevance

results this study are consistent engagement insulin, Akt, pathways provide context clinical findings trial. This potential exosome-based biomarkers objective trials

Language: Английский

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Brain Insulin Resistance and Hippocampal Plasticity: Mechanisms and Biomarkers of Cognitive Decline

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: July 31, 2019

In the last decade, much attention has been devoted to effects of nutrient-related signals on brain development and cognitive functions. A turning point was discovery that areas other than hypothalamus expressed receptors for hormones related metabolism. particular, insulin signaling demonstrated impact molecular cascades underlying hippocampal plasticity, learning memory. Here, we summarize evidence linking alteration sensitivity with changes both adult neurogenesis synaptic plasticity. We also review epidemiological studies experimental models emphasizing critical role resistance at crossroad between metabolic neurodegenerative disease. Finally, brief novel findings suggesting how biomarkers resistance, involving study brain-derived extracellular vesicles glucose metabolism, may predict onset and/or progression decline.

Language: Английский

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Role of the Blood-Brain Barrier in Central Nervous System Insulin Resistance

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: June 4, 2019

The blood-brain barrier (BBB) mediates the communication between periphery and central nervous system (CNS). Recently, CNS insulin resistance has been elucidated to play a role in neurodegenerative disease. This stimulated wealth of information on molecular impact brain, particularly improvement cognition. Since BBB regulates transport into brain thus, helps regulate levels, alterations response could resistance. In this review, we summarize effect some cell types that make up BBB, including endothelial cells, neurons, astrocytes, pericytes. We broadly discuss how these changes specific ultimately BBB. also can levels pathological hallmarks Alzheimer's disease, amyloid beta (Aβ) tau within each type. Finally, suggest interventional approaches overcome detrimental effects regards transport.

Language: Английский

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Insulin Resistance and Oxidative Stress in the Brain: What’s New?

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(4), P. 874 - 874

Published: Feb. 18, 2019

The latest studies have indicated a strong relationship between systemic insulin resistance (IR) and higher incidence of neurodegeneration, dementia, mild cognitive impairment. Although some these abnormalities could be explained by chronic hyperglycaemia, hyperinsulinemia, dyslipidaemia, and/or prolonged whole-body inflammation, the key role is attributed to neuronal redox imbalance oxidative damage. In this mini review, we provide schematic overview intracellular stress mitochondrial in IR brain. We highlight important correlations found so far brain stress, ceramide generation, β-amyloid accumulation, as well apoptosis conditions.

Language: Английский

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Insulin signaling in the hippocampus and amygdala regulates metabolism and neurobehavior

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(13), P. 6379 - 6384

Published: Feb. 14, 2019

Significance Loss of insulin receptors in the brain causes metabolic and behavioral abnormalities whereas loss IGF-1 leads to a developmental defect periphery. However, less is known about impact receptor (IR/IGF1R) adult mice, especially higher neural processing regions. Here, we show that IR/IGF1R hippocampus central amygdala mice results decrease glutamate receptors, accompanied by glucose intolerance, anxiety-like behavior, impaired cognition. In addition, identify an insulin/IGF-1 signaling-dependent circuit originating from amygdala, which regulates interscapular brown fat activity thermogenesis. Thus, signaling important for systemic metabolism.

Language: Английский

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