{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:30:28Z","timestamp":1790299828437,"version":"4.1.0"},"reference-count":97,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["CEEC IND\/02428\/2018"],"award-info":[{"award-number":["CEEC IND\/02428\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["443257\/2023\\u20130"],"award-info":[{"award-number":["443257\/2023\\u20130"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019598","name":"Portuguese Society of Diabetology","doi-asserted-by":"publisher","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}],"id":[{"id":"10.13039\/100019598","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019598","name":"Portuguese Society of Diabetology","doi-asserted-by":"publisher","award":["UID\/4462\/2025"],"award-info":[{"award-number":["UID\/4462\/2025"]}],"id":[{"id":"10.13039\/100019598","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003381","name":"Minist\u00e9rio da Educa\u00e7\u00e3o e Ci\u00eancia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["2022.11376"],"award-info":[{"award-number":["2022.11376"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["2022.12291"],"award-info":[{"award-number":["2022.12291"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.phrs.2026.108140","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:10:24Z","timestamp":1770970224000},"page":"108140","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Chronic caffeine consumption prevents obesity-induced cognitive and memory impairments by reducing neuroinflammation and enhancing neuronal activity in the hippocampus"],"prefix":"10.1016","volume":"225","author":[{"given":"Adriana M.","family":"Capucho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Ponce","family":"de Le\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine Correa","family":"Flor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gon\u00e7alo M.","family":"Melo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Vinicius","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana F.","family":"Sacramento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00edlvia V.","family":"Conde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phrs.2026.108140_bib1","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/731685","article-title":"Beyond obesity and lifestyle: a review of 21st century chronic disease determinants","volume":"2014","author":"Egger","year":"2014","journal-title":"Biomed. Res Int."},{"issue":"4","key":"10.1016\/j.phrs.2026.108140_bib2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.beem.2005.07.010","article-title":"Link between obesity and type 2 diabetes","volume":"19","author":"Golay","year":"2005","journal-title":"Best. Pr. Res Clin. Endocrinol. Metab."},{"issue":"7","key":"10.1016\/j.phrs.2026.108140_bib3","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1001\/jama.2014.8040","article-title":"The mental health comorbidities of diabetes","volume":"312","author":"Ducat","year":"2014","journal-title":"JAMA"},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib4","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41398-023-02447-w","article-title":"Obesity as pleiotropic risk state for metabolic and mental health throughout life","volume":"13","author":"Leutner","year":"2023","journal-title":"Transl. Psychiatry"},{"issue":"6","key":"10.1016\/j.phrs.2026.108140_bib5","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/dme.13611","article-title":"Prevalence and correlates of depressive disorders in people with Type 2 diabetes: results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study, a collaborative study carried out in 14 countries","volume":"35","author":"Lloyd","year":"2018","journal-title":"Diabet. Med."},{"issue":"2","key":"10.1016\/j.phrs.2026.108140_bib6","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jpsychores.2012.11.013","article-title":"Association of diabetes with anxiety: a systematic review and meta-analysis","volume":"74","author":"Smith","year":"2013","journal-title":"J. Psychosom. Res"},{"issue":"2","key":"10.1016\/j.phrs.2026.108140_bib7","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/ijo.2008.268","article-title":"Depression and anxiety among US adults: associations with body mass index","volume":"33","author":"Zhao","year":"2009","journal-title":"Int J. Obes. (Lond. )"},{"issue":"3","key":"10.1016\/j.phrs.2026.108140_bib8","doi-asserted-by":"crossref","first-page":"726","DOI":"10.2337\/diacare.28.3.726","article-title":"The effects of type 1 diabetes on cognitive performance: a meta-analysis","volume":"28","author":"Brands","year":"2005","journal-title":"Diabetes Care"},{"key":"10.1016\/j.phrs.2026.108140_bib9","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1042\/BST0331041","article-title":"Utrecht Diabetic Encephalopathy Study Group. Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology?","volume":"33","author":"Biessels","year":"2005","journal-title":"Biochem Soc. Trans."},{"issue":"8","key":"10.1016\/j.phrs.2026.108140_bib10","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1001\/archneur.59.8.1258","article-title":"Caloric intake and the risk of Alzheimer disease","volume":"59","author":"Luchsinger","year":"2002","journal-title":"Arch. Neurol."},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib11","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neurobiolaging.2005.08.019","article-title":"Obesity, diabetes and cognitive deficit: The Framingham Heart Study","volume":"26","author":"Elias","year":"2005","journal-title":"Neurobiol. Aging"},{"issue":"2-3","key":"10.1016\/j.phrs.2026.108140_bib12","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000082659","article-title":"Interactive effect of obesity indexes on cognition","volume":"19","author":"Jeong","year":"2005","journal-title":"Dement Geriatr. Cogn. Disord."},{"key":"10.1016\/j.phrs.2026.108140_bib13","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3389\/fnins.2014.00375","article-title":"Obesity and cognitive decline: role of inflammation and vascular changes","volume":"8","author":"Nguyen","year":"2014","journal-title":"Front Neurosci."},{"issue":"2","key":"10.1016\/j.phrs.2026.108140_bib14","doi-asserted-by":"crossref","first-page":"474","DOI":"10.2337\/diabetes.53.2.474","article-title":"Increased risk of type 2 diabetes in Alzheimer disease","volume":"53","author":"Janson","year":"2004","journal-title":"Diabetes"},{"key":"10.1016\/j.phrs.2026.108140_bib15","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.3389\/fnins.2018.01015","article-title":"Impact of caffeine consumption on Type 2 diabetes-induced spatial memory impairment and neurochemical alterations in the hippocampus","volume":"12","author":"Duarte","year":"2019","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.phrs.2026.108140_bib16","first-page":"237","article-title":"Brain insulin signaling and cognition: Possible links","volume":"22","author":"Yaribeygi","year":"2023","journal-title":"EXCLI J."},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib17","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/WAD.0000000000000182","article-title":"High Hemoglobin A1c and Diabetes Predict Memory Decline in the Health and Retirement Study","volume":"31","author":"Marden","year":"2017","journal-title":"Alzheimer Dis. Assoc. Disord."},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib18","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00125-019-04986-8","article-title":"Association between visit-to-visit variability of HbA1c and cognitive decline: a pooled analysis of two prospective population-based cohorts","volume":"63","author":"Yu","year":"2020","journal-title":"Diabetologia"},{"issue":"4","key":"10.1016\/j.phrs.2026.108140_bib19","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.tins.2017.02.005","article-title":"Obesity-Induced Neuroinflammation: Beyond the Hypothalamus","volume":"40","author":"Guillemot-Legris","year":"2017","journal-title":"Trends Neurosci."},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib20","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3390\/metabo13010086","article-title":"Obesity-Induced Brain Neuroinflammatory and Mitochondrial Changes","volume":"13","author":"Schmitt","year":"2023","journal-title":"Metabolites"},{"key":"10.1016\/j.phrs.2026.108140_bib21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/bs.irn.2023.04.006","article-title":"Effects of adenosine A2A receptors on cognitive function in health and disease","volume":"170","author":"Garcia","year":"2023","journal-title":"Int Rev. Neurobiol."},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/jnc.14841","article-title":"The role of adenosine receptors in mood and anxiety disorders","volume":"151","author":"van Calker","year":"2019","journal-title":"J. Neurochem."},{"key":"10.1016\/j.phrs.2026.108140_bib23","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neuropharm.2017.08.027","article-title":"Cognitive impairments associated with alterations in synaptic proteins induced by the genetic loss of adenosine A2A receptors in mice","volume":"126","author":"Moscoso-Castro","year":"2017","journal-title":"Neuropharmacology"},{"issue":"8","key":"10.1016\/j.phrs.2026.108140_bib24","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.3390\/biom13081173","article-title":"Adenosine A2A Receptor Up-Regulation Pre-Dates Deficits of Synaptic Plasticity and of Memory in Mice Exposed to A\u03b21-42 to Model Early Alzheimer's Disease","volume":"13","author":"Lopes","year":"2023","journal-title":"Biomolecules"},{"key":"10.1016\/j.phrs.2026.108140_bib25","article-title":"Adenosine A2A signaling in mood disorders: how far have we come?","author":"Bevilacqua","year":"2024","journal-title":"IBRO Neurosci. Rep."},{"key":"10.1016\/j.phrs.2026.108140_bib26","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3389\/fncel.2020.00202","article-title":"Neuroprotective Effects of Adenosine A1 Receptor Signaling on Cognitive Impairment Induced by Chronic Intermittent Hypoxia in Mice","volume":"14","author":"Zhang","year":"2020","journal-title":"Front. Cell Neurosci."},{"issue":"4","key":"10.1016\/j.phrs.2026.108140_bib27","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.1007\/s12035-017-0571-x","article-title":"Adenosine A1 Receptors Play an Important Protective Role Against Cognitive Impairment and Long-Term Potentiation Inhibition in a Pentylenetetrazol Mouse Model of Epilepsy","volume":"55","author":"Zhou","year":"2018","journal-title":"Mol. Neurobiol."},{"issue":"8023","key":"10.1016\/j.phrs.2026.108140_bib28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41586-024-07611-w","article-title":"Adenosine signalling to astrocytes coordinates brain metabolism and function","volume":"632","author":"Theparambil","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.phrs.2026.108140_bib29","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0031-6997(24)01396-6","article-title":"Actions of caffeine in the brain with special reference to factors that contribute to its widespread use","volume":"51","author":"Fredholm","year":"1999","journal-title":"Pharm. Rev."},{"key":"10.1016\/j.phrs.2026.108140_bib30","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1017\/S0007114511002406","article-title":"Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats","volume":"107","author":"Conde","year":"2012","journal-title":"Br. J. Nutr."},{"issue":"10","key":"10.1016\/j.phrs.2026.108140_bib31","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.nut.2012.02.013","article-title":"Caffeine attenuates metabolic syndrome in diet-induced obese rats","volume":"28","author":"Panchal","year":"2012","journal-title":"Nutrition"},{"issue":"5","key":"10.1016\/j.phrs.2026.108140_bib32","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1007\/s11357-012-9475-x","article-title":"Chronic caffeine intake reverses age-induced insulin resistance in the rat: effect on skeletal muscle Glut4 transporters and AMPK activity","volume":"35","author":"Guarino","year":"2013","journal-title":"Age"},{"issue":"2","key":"10.1016\/j.phrs.2026.108140_bib33","doi-asserted-by":"crossref","first-page":"569","DOI":"10.2337\/dc13-1203","article-title":"Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis","volume":"37","author":"Ding","year":"2014","journal-title":"Diabetes Care"},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib34","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1001\/jama.294.1.97","article-title":"Coffee consumption and risk of type 2 diabetes: a systematic review","volume":"294","author":"van Dam","year":"2005","journal-title":"JAMA"},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib35","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.124.034365","article-title":"Swiss-AF investigators. Coffee Consumption Correlates With Better Cognitive Performance in Patients With a High Incidence for Stroke","volume":"14","author":"Barbagallo","year":"2025","journal-title":"J. Am. Heart Assoc."},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib36","doi-asserted-by":"crossref","first-page":"S95","DOI":"10.3233\/JAD-2010-1408","article-title":"Chronic caffeine consumption prevents memory disturbance in different animal models of memory decline","volume":"20","author":"Cunha","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.phrs.2026.108140_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.psychres.2023.115307","article-title":"The association between coffee consumption and risk of incident depression and anxiety: Exploring the benefits of moderate intake","volume":"326","author":"Min","year":"2023","journal-title":"Psychiatry Res"},{"issue":"2","key":"10.1016\/j.phrs.2026.108140_bib38","doi-asserted-by":"crossref","first-page":"413","DOI":"10.3233\/JAD-122371","article-title":"Caffeine and cognitive decline in elderly women at high vascular risk","volume":"35","author":"Vercambre","year":"2013","journal-title":"J. Alzheimers Dis."},{"issue":"3","key":"10.1016\/j.phrs.2026.108140_bib39","doi-asserted-by":"crossref","first-page":"C375","DOI":"10.1152\/ajpcell.00379.2020","article-title":"Adipose tissue inflammation and metabolic dysfunction in obesity","volume":"320","author":"Kawai","year":"2021","journal-title":"Am. J. Physiol. Cell Physiol."},{"issue":"9","key":"10.1016\/j.phrs.2026.108140_bib40","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1007\/s13205-025-04468-2","article-title":"Implicating neuroinflammation in hippocampus, prefrontal cortex and amygdala with cognitive deficit: a narrative review","volume":"15","author":"Blossom","year":"2025","journal-title":"3 Biotech"},{"issue":"6","key":"10.1016\/j.phrs.2026.108140_bib41","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.3390\/nu11061197","article-title":"Evaluating the Impact of Different Hypercaloric Diets on Weight Gain, Insulin Resistance, Glucose Intolerance, and its Comorbidities in Rats","volume":"11","author":"Melo","year":"2019","journal-title":"Nutrients"},{"key":"10.1016\/j.phrs.2026.108140_bib42","article-title":"Chronic caffeine intake restores insulin sensitivity in high-sucrose diet rats through adaptations in adipose tissue metabolism","volume":"58","author":"Coelho","year":"2015","journal-title":"Diabetologia"},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib43","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/s00125-016-4133-y","article-title":"Functional abolition of carotid body activity restores insulin action and glucose homeostasis in rats: key roles for visceral adipose tissue and the liver","volume":"60","author":"Sacramento","year":"2017","journal-title":"Diabetologia"},{"issue":"3","key":"10.1016\/j.phrs.2026.108140_bib44","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1007\/s00125-017-4533-7","article-title":"Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes","volume":"61","author":"Sacramento","year":"2018","journal-title":"Diabetologia"},{"issue":"8","key":"10.1016\/j.phrs.2026.108140_bib45","doi-asserted-by":"crossref","first-page":"866","DOI":"10.6026\/97320630019866","article-title":"A short review on behavioural assessment methods in rodents","volume":"19","author":"K S V","year":"2023","journal-title":"Bioinformation"},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib46","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3390\/nu16010067","article-title":"Overnutrition during Pregnancy and Lactation Induces Gender-Dependent Dysmetabolism in the Offspring Accompanied by Heightened Stress and Anxiety","volume":"16","author":"Melo","year":"2023","journal-title":"Nutrients"},{"issue":"21","key":"10.1016\/j.phrs.2026.108140_bib47","doi-asserted-by":"crossref","first-page":"3590","DOI":"10.1021\/acschemneuro.0c00466","article-title":"Western Diet Accelerates the Impairment of Odor-Related Learning and Olfactory Memory in the Mouse","volume":"11","author":"Lietzau","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.phrs.2026.108140_bib48","series-title":"The Rat Brain in Stereotaxic Coordinates","author":"Paxinos","year":"1982"},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib49","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0147733","article-title":"A Comprehensive Behavioral Test Battery to Assess Learning and Memory in 129S6\/Tg2576 Mice","volume":"11","author":"Wolf","year":"2016","journal-title":"PLoS One"},{"issue":"11","key":"10.1016\/j.phrs.2026.108140_bib50","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1073\/pnas.1500877112","article-title":"Insulin resistance in brain alters dopamine turnover and causes behavioral disorders","volume":"112","author":"Kleinridders","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.phrs.2026.108140_bib51","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3389\/fpsyt.2019.00057","article-title":"Insulin Resistance as a Shared Pathogenic Mechanism Between Depression and Type 2 Diabetes","volume":"10","author":"Lyra E Silva","year":"2019","journal-title":"Front Psychiatry"},{"key":"10.1016\/j.phrs.2026.108140_bib52","doi-asserted-by":"crossref","first-page":"629","DOI":"10.3389\/fnins.2019.00629","article-title":"Altered Insulin Signaling in Alzheimer's Disease Brain - Special Emphasis on PI3K-Akt Pathway","volume":"13","author":"Gabbouj","year":"2019","journal-title":"Front Neurosci."},{"issue":"51","key":"10.1016\/j.phrs.2026.108140_bib53","doi-asserted-by":"crossref","first-page":"15731","DOI":"10.1073\/pnas.1511593112","article-title":"Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function","volume":"112","author":"Bocarsly","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"4","key":"10.1016\/j.phrs.2026.108140_bib54","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0021899","article-title":"Caffeine consumption prevents diabetes-induced memory impairment and synaptotoxicity in the hippocampus of NONcZNO10\/LTJ mice","volume":"7","author":"Duarte","year":"2012","journal-title":"PLoS One"},{"issue":"6","key":"10.1016\/j.phrs.2026.108140_bib55","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1038\/s41390-021-01924-6","article-title":"Caffeine treatment started before injury reduces hypoxic-ischemic white-matter damage in neonatal rats by regulating phenotypic microglia polarization","volume":"92","author":"Yang","year":"2022","journal-title":"Pedia Res"},{"key":"10.1016\/j.phrs.2026.108140_bib56","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fncel.2018.00049","article-title":"Caffeine and Modafinil Ameliorate the Neuroinflammation and Anxious Behavior in Rats during Sleep Deprivation by Inhibiting the Microglia Activation","volume":"12","author":"Wadhwa","year":"2018","journal-title":"Front Cell Neurosci."},{"key":"10.1016\/j.phrs.2026.108140_bib57","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/4761081","article-title":"Having a Coffee Break: The Impact of Caffeine Consumption on Microglia-Mediated Inflammation in Neurodegenerative Diseases","volume":"2017","author":"Madeira","year":"2017","journal-title":"Mediat. Inflamm."},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib58","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s12031-021-01894-8","article-title":"Caffeine Inhibits Activation of the NLRP3 Inflammasome via Autophagy to Attenuate Microglia-Mediated Neuroinflammation in Experimental Autoimmune Encephalomyelitis","volume":"72","author":"Wang","year":"2022","journal-title":"J. Mol. Neurosci."},{"key":"10.1016\/j.phrs.2026.108140_bib59","doi-asserted-by":"crossref","DOI":"10.1016\/j.physbeh.2024.114697","article-title":"Therapeutic effects of alpha lipoic acid and\/or caffeine-loaded chitosan nanoparticles on memory impairment and neurochemical changes in high-fat diet-induced obese rats","volume":"287","author":"Hosny","year":"2024","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.phrs.2026.108140_bib60","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.physbeh.2012.11.008","article-title":"Caffeine prevents weight gain and cognitive impairment caused by a high-fat diet while elevating hippocampal BDNF","volume":"109","author":"Moy","year":"2013","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.phrs.2026.108140_bib61","doi-asserted-by":"crossref","DOI":"10.2174\/1567205020666230605113856","article-title":"Caffeine improves memory and cognition via modulating neural progenitor cell survival and decreasing oxidative stress in Alzheimer's rat model","author":"Tiwari","year":"2023","journal-title":"Curr. Alzheimer Res"},{"issue":"12","key":"10.1016\/j.phrs.2026.108140_bib62","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.3390\/molecules27123737","article-title":"Neuroprotective Effect of Caffeine in Alzheimer's Disease","volume":"27","author":"M Yelanchezian","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.phrs.2026.108140_bib63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pbr.2024.06.001","article-title":"Coffee and Parkinson's disease","volume":"289","author":"Asuku","year":"2024","journal-title":"Prog. Brain Res"},{"key":"10.1016\/j.phrs.2026.108140_bib64","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2020.602697","article-title":"Caffeine and Parkinson's Disease: Multiple Benefits and Emerging Mechanisms","volume":"14","author":"Ren","year":"2020","journal-title":"Front Neurosci."},{"issue":"5","key":"10.1016\/j.phrs.2026.108140_bib65","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1093\/gerona\/gly090","article-title":"Age Modulates the Association of Caffeine Intake With Cognition and With Gray Matter in Elderly Diabetics","volume":"74","author":"West","year":"2019","journal-title":"J. Gerontol. A Biol. Sci. Med Sci."},{"issue":"25","key":"10.1016\/j.phrs.2026.108140_bib66","doi-asserted-by":"crossref","first-page":"7833","DOI":"10.1073\/pnas.1423088112","article-title":"Caffeine acts through neuronal adenosine A2A receptors to prevent mood and memory dysfunction triggered by chronic stress","volume":"112","author":"Kaster","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib67","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3390\/biom13010106","article-title":"Effects of chronic caffeine consumption on synaptic function, metabolism and adenosine modulation in different brain areas","volume":"13","author":"Lopes","year":"2023","journal-title":"Biomolecules"},{"issue":"5","key":"10.1016\/j.phrs.2026.108140_bib68","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1007\/s10519-020-10003-1","article-title":"Effects of Chronic Caffeine Administration on Behavioral and Molecular Adaptations to Sensory Contact Model Induced Stress in Adolescent Male Mice","volume":"50","author":"Ibrahim","year":"2020","journal-title":"Behav. Genet"},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib69","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1038\/s41598-024-52599-y","article-title":"Caffeine supplementation improves the cognitive abilities and shooting performance of elite e-sports players: a crossover trial","volume":"14","author":"Wu","year":"2024","journal-title":"Sci. Rep."},{"issue":"19","key":"10.1016\/j.phrs.2026.108140_bib70","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1111\/bph.13919","article-title":"Glutamatergic regulation of cognition and functional brain connectivity: insights from pharmacological, genetic and translational schizophrenia research","volume":"174","author":"Dauvermann","year":"2017","journal-title":"Br. J. Pharm."},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib71","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2174\/1570159X113119990045","article-title":"Purinergic signaling and hippocampal long-term potentiation","volume":"12","author":"D\u00fcster","year":"2014","journal-title":"Curr. Neuropharmacol."},{"issue":"7","key":"10.1016\/j.phrs.2026.108140_bib72","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1093\/scan\/nsr058","article-title":"Storm in a coffee cup: caffeine modifies brain activation to social signals of threat","volume":"7","author":"Smith","year":"2012","journal-title":"Soc. Cogn. Affect Neurosci."},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib73","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2174\/1570159X13666141210215655","article-title":"M. Caffeine: cognitive and physical performance enhancer or psychoactive drug?","volume":"13","author":"Cappelletti","year":"2015","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.phrs.2026.108140_bib74","article-title":"Caffeine intake and anxiety: a meta-analysis","volume":"15","author":"Liu","year":"2024","journal-title":"Front Psychol."},{"issue":"2","key":"10.1016\/j.phrs.2026.108140_bib75","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s002130050037","article-title":"The anxiogenic-like effect of caffeine in two experimental procedures measuring anxiety in the mouse is not shared by selective A(2A) adenosine receptor antagonists","volume":"148","author":"El Yacoubi","year":"2000","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.phrs.2026.108140_bib76","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ejps.2015.01.011","article-title":"Disclosing caffeine action on insulin sensitivity: effects on rat skeletal muscle","volume":"70","author":"Sacramento","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib77","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s12929-021-00766-y","article-title":"Emerging roles of dysregulated adenosine homeostasis in brain disorders with a specific focus on neurodegenerative diseases","volume":"28","author":"Chang","year":"2021","journal-title":"J. Biomed. Sci."},{"key":"10.1016\/j.phrs.2026.108140_bib78","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.116996","article-title":"Adenosine and adenosine receptors in metabolic imbalance-related neurological issues","volume":"177","author":"Jang","year":"2024","journal-title":"Biomed. Pharm."},{"issue":"24","key":"10.1016\/j.phrs.2026.108140_bib79","doi-asserted-by":"crossref","first-page":"9697","DOI":"10.3390\/ijms21249697","article-title":"A2B Adenosine Receptors: When Outsiders May Become an Attractive Target to Treat Brain Ischemia or Demyelination","volume":"21","author":"Coppi","year":"2020","journal-title":"Int J. Mol. Sci."},{"key":"10.1016\/j.phrs.2026.108140_bib80","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2020.588757","article-title":"Protective effect of adenosine A2B receptor agonist, BAY60-6583, against transient focal brain ischemia in rat","volume":"11","author":"Dettori","year":"2021","journal-title":"Front Pharm."},{"key":"10.1016\/j.phrs.2026.108140_bib81","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.brainresbull.2019.05.018","article-title":"Functional characterization of a novel adenosine A2B receptor agonist on short-term plasticity and synaptic inhibition during oxygen and glucose deprivation in the rat CA1 hippocampus","volume":"151","author":"Fusco","year":"2019","journal-title":"Brain Res Bull."},{"issue":"3","key":"10.1016\/j.phrs.2026.108140_bib82","first-page":"108","article-title":"Adenosine kinase is a new therapeutic target to prevent ischemic neuronal death","volume":"2","author":"Boison","year":"2010","journal-title":"Open Drug Discov. J."},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib83","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/cercor\/bhs284","article-title":"Homeostatic control of synaptic activity by endogenous adenosine is mediated by adenosine kinase","volume":"24","author":"Di\u00f3genes","year":"2014","journal-title":"Cereb. Cortex"},{"issue":"10","key":"10.1016\/j.phrs.2026.108140_bib84","doi-asserted-by":"crossref","DOI":"10.1111\/obr.13490","article-title":"Pathophysiology roles for adenosine 2A receptor in obesity and related diseases","volume":"23","author":"Cai","year":"2022","journal-title":"Obes. Rev."},{"issue":"3","key":"10.1016\/j.phrs.2026.108140_bib85","doi-asserted-by":"crossref","first-page":"850","DOI":"10.2337\/db13-0573","article-title":"A2B adenosine receptors prevent insulin resistance by inhibiting adipose tissue inflammation via maintaining alternative macrophage activation","volume":"63","author":"Cs\u00f3ka","year":"2014","journal-title":"Diabetes"},{"issue":"3","key":"10.1016\/j.phrs.2026.108140_bib86","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1530\/JOE-18-0169","article-title":"Regulation of adipose tissue inflammation by adenosine 2A receptor in obese mice","volume":"239","author":"Pei","year":"2018","journal-title":"J. Endocrinol."},{"key":"10.1016\/j.phrs.2026.108140_bib87","doi-asserted-by":"crossref","first-page":"899","DOI":"10.3389\/fphar.2017.00899","article-title":"Caffeine Controls Glutamatergic Synaptic Transmission and Pyramidal Neuron Excitability in Human Neocortex","volume":"8","author":"Kerkhofs","year":"2018","journal-title":"Front Pharm."},{"issue":"4","key":"10.1016\/j.phrs.2026.108140_bib88","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s11302-020-09724-z","article-title":"Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus","volume":"16","author":"Martins","year":"2020","journal-title":"Purinergic Signal"},{"issue":"1","key":"10.1016\/j.phrs.2026.108140_bib89","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1096\/fj.11-190934","article-title":"Adenosine promotes alternative macrophage activation via A2A and A2B receptors","volume":"26","author":"Cs\u00f3ka","year":"2012","journal-title":"FASEB J."},{"issue":"7","key":"10.1016\/j.phrs.2026.108140_bib90","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/nn.2341","article-title":"Adenosine A(2A) receptor mediates microglial process retraction","volume":"12","author":"Orr","year":"2009","journal-title":"Nat. Neurosci."},{"issue":"6","key":"10.1016\/j.phrs.2026.108140_bib91","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1111\/jnc.13724","article-title":"How does adenosine control neuronal dysfunction and neurodegeneration?","volume":"139","author":"Cunha","year":"2016","journal-title":"J. Neurochem."},{"issue":"10","key":"10.1016\/j.phrs.2026.108140_bib92","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2017.451","article-title":"Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage","volume":"8","author":"Boia","year":"2017","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.phrs.2026.108140_bib93","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3389\/fnins.2015.00037","article-title":"Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods","volume":"9","author":"Barth","year":"2015","journal-title":"Front. Neurosci."},{"issue":"1-2","key":"10.1016\/j.phrs.2026.108140_bib94","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/jnr.23809","article-title":"Understanding the broad influence of sex hormones and sex differences in the brain","volume":"95","author":"McEwen","year":"2017","journal-title":"J. Neurosci. Res"},{"issue":"3","key":"10.1016\/j.phrs.2026.108140_bib95","doi-asserted-by":"crossref","DOI":"10.1093\/sleep\/zsab225","article-title":"Estradiol influences adenosinergic signaling and nonrapid eye movement sleep need in adult female rats","volume":"45","author":"Smith","year":"2022","journal-title":"Sleep"},{"issue":"4","key":"10.1016\/j.phrs.2026.108140_bib96","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/BF00165391","article-title":"Effect of long term caffeine treatment on A1 and A2 adenosine receptor binding and on mRNA levels in rat brain","volume":"347","author":"Johansson","year":"1993","journal-title":"Naunyn Schmiede Arch. Pharm."},{"issue":"1-2","key":"10.1016\/j.phrs.2026.108140_bib97","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0006-8993(93)91672-F","article-title":"Long-term caffeine treatment leads to a decreased susceptibility to NMDA-induced clonic seizures in mice without changes in adenosine A1 receptor number","volume":"612","author":"Georgiev","year":"1993","journal-title":"Brain Res"}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661826000551?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661826000551?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T03:28:57Z","timestamp":1777606137000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661826000551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":97,"alternative-id":["S1043661826000551"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2026.108140","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Chronic caffeine consumption prevents obesity-induced cognitive and memory impairments by reducing neuroinflammation and enhancing neuronal activity in the hippocampus","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2026.108140","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"108140"}}