{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T04:44:55Z","timestamp":1792903495026,"version":"4.5.0"},"reference-count":134,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS Grant-in-Aid for Exploratory Research","doi-asserted-by":"publisher","award":["18K18454"],"award-info":[{"award-number":["18K18454"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The brain-derived neurotrophic factor (BDNF) is an extensively studied neurotrophin es sential for both developing the brain and maintaining adult brain function. In the adult hippocampus, BDNF is critical for maintaining adult neurogenesis. Adult hippocampal neurogenesis is involved not only in memory formation and learning ability, but also mood regulation and stress responses. Accordingly, decreased levels of BDNF, accompanied by low levels of adult neurogenesis, occurs in brains of older adults with impaired cognitive function and in those of patients with major depression disorder. Therefore, elucidating the mechanisms that maintain hippocampal BDNF levels is biologically and clinically important. It has been revealed that signalling from peripheral tissues contribute to the regulation of BDNF expression in the brain across the blood\u2013brain barrier. Moreover, recent studies indicated evidence that neuronal pathways can also be a mechanism by which peripheral tissues signal to the brain for the regulation of BDNF expression. In this review, we give an overview of the current status in the regulation of central BDNF expression by peripheral signalling, with a special interest in the regulation of hippocampal BDNF levels by signals via the vagus nerve. Finally, we discuss the relationship between signalling from peripheral tissues and age-associated control of central BDNF expression.<\/jats:p>","DOI":"10.3390\/ijms24043543","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T02:56:13Z","timestamp":1675997773000},"page":"3543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Peripheral Regulation of Central Brain-Derived Neurotrophic Factor Expression through the Vagus Nerve"],"prefix":"10.3390","volume":"24","author":[{"given":"Yoko","family":"Amagase","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichi","family":"Kambayashi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3024-460X","authenticated-orcid":false,"given":"Yoshinori","family":"Takei","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6854","DOI":"10.1523\/JNEUROSCI.2976-17.2018","article-title":"Adult Neurogenesis Conserves Hippocampal Memory Capacity","volume":"38","author":"Alam","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"852680","DOI":"10.3389\/fnins.2022.852680","article-title":"What Is Adult Hippocampal Neurogenesis Good for","volume":"16","author":"Kempermann","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ynstr.2014.11.003","article-title":"Role of adult hippocampal neurogenesis in stress resilience","volume":"1","author":"Levone","year":"2015","journal-title":"Neurobiol. Stress"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41380-021-01136-8","article-title":"Adult hippocampal neurogenesis shapes adaptation and improves stress response: A mechanistic and integrative perspective","volume":"27","author":"Surget","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41539-022-00133-y","article-title":"Dissecting the role of adult hippocampal neurogenesis towards resilience versus susceptibility to stress-related mood disorders","volume":"7","author":"Jones","year":"2022","journal-title":"NPJ Sci. Learn."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5967","DOI":"10.1523\/JNEUROSCI.0110-07.2007","article-title":"Epigenetic modulation of seizure-induced neurogenesis and cognitive decline","volume":"27","author":"Jessberger","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1523\/JNEUROSCI.5655-09.2010","article-title":"The developmental stage of dentate granule cells dictates their contribution to seizure-induced plasticity","volume":"30","author":"Kron","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_8","first-page":"552","article-title":"Neurogenesis within the adult hippocampus under physiological conditions and in depression","volume":"7","author":"Dokter","year":"2012","journal-title":"Neural Regen. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/hipo.20153","article-title":"Is there a link between adult neurogenesis and learning","volume":"16","author":"Leuner","year":"2006","journal-title":"Hippocampus"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"a018812","DOI":"10.1101\/cshperspect.a018812","article-title":"Neurogenesis in the Adult Hippocampus","volume":"7","author":"Kempermann","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40035-018-0109-9","article-title":"Factors that influence adult neurogenesis as potential therapy","volume":"7","author":"Shohayeb","year":"2018","journal-title":"Transl. Neurodegener."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1073\/pnas.1015950108","article-title":"Exercise training increases size of hippocampus and improves memory","volume":"108","author":"Erickson","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/ageing\/afu010","article-title":"The effects of multimodal exercise on cognitive and physical functioning and brain-derived neurotrophic factor in older women: A randomised controlled trial","volume":"43","author":"Vaughan","year":"2014","journal-title":"Age Ageing"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.celrep.2018.02.001","article-title":"Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain","volume":"22","author":"Gontier","year":"2018","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1126\/science.1251141","article-title":"Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors","volume":"344","author":"Katsimpardi","year":"2014","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/s41591-019-0440-4","article-title":"Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1","volume":"25","author":"Yousef","year":"2019","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.neuron.2019.02.008","article-title":"Gut Microbe to Brain Signaling: What Happens in Vagus\u2026","volume":"101","author":"Dinan","year":"2019","journal-title":"Neuron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1007\/s11357-022-00579-3","article-title":"Alteration in peritoneal cells with the chemokine CX3CL1 reverses age-associated impairment of recognition memory","volume":"44","author":"Takei","year":"2022","journal-title":"Geroscience"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrn3379","article-title":"Neurotrophin regulation of neural circuit development and function","volume":"14","author":"Park","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_20","first-page":"799","article-title":"Studies on the physiological role of brain-derived neurotrophic factor and neurotrophin-3 in knockout mice","volume":"39","author":"Ernfors","year":"1995","journal-title":"Int. J. Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1111\/j.1460-9568.1997.tb01687.x","article-title":"Learning deficit in BDNF mutant mice","volume":"9","author":"Linnarsson","year":"1997","journal-title":"Eur. J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1046\/j.1471-4159.2002.01085.x","article-title":"Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice","volume":"82","author":"Lee","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/sj.mp.4001957","article-title":"Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories","volume":"12","author":"Heldt","year":"2007","journal-title":"Mol. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e253","DOI":"10.1038\/tp.2013.30","article-title":"BDNF overexpression in mouse hippocampal astrocytes promotes local neurogenesis and elicits anxiolytic-like activities","volume":"3","author":"Quesseveur","year":"2013","journal-title":"Transl. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8856","DOI":"10.1073\/pnas.92.19.8856","article-title":"Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor","volume":"92","author":"Korte","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"14318","DOI":"10.1523\/JNEUROSCI.0709-12.2012","article-title":"BDNF promotes differentiation and maturation of adult-born neurons through GABAergic transmission","volume":"32","author":"Waterhouse","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1212\/WNL.0000000000002387","article-title":"Higher brain BDNF gene expression is associated with slower cognitive decline in older adults","volume":"86","author":"Buchman","year":"2016","journal-title":"Neurology"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Numakawa, T., and Odaka, H. (2022). The Role of Neurotrophin Signaling in Age-Related Cognitive Decline and Cognitive Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147726"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Suda, K., and Matsuda, K. (2022). How Microbes Affect Depression: Underlying Mechanisms via the Gut-Brain Axis and the Modulating Role of Probiotics. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031172"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/nrneurol.2009.54","article-title":"Brain-derived neurotrophic factor in neurodegenerative diseases","volume":"5","author":"Zuccato","year":"2009","journal-title":"Nat. Rev. Neurol."},{"key":"ref_31","unstructured":"Tubbs, R.S., Rizk, E., Shoja, M.M., Loukas, M., Barbaro, N., and Spinner, R.J. (2015). Nerves and Nerve Injuries: Vol 1: History, Embryology, Anatomy, Imaging, and Diagnostics, Academic Press."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e12643","DOI":"10.1111\/jne.12643","article-title":"The role of the vagus nerve in appetite control: Implications for the pathogenesis of obesity","volume":"30","author":"Cork","year":"2018","journal-title":"J. Neuroendocr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3389\/fpsyt.2018.00044","article-title":"Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders","volume":"9","author":"Breit","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1080\/10253890.2020.1859475","article-title":"Brain mechanisms of HPA axis regulation: Neurocircuitry and feedback in context Richard Kvetnansky lecture","volume":"23","author":"Herman","year":"2020","journal-title":"Stress"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"143770","DOI":"10.1172\/JCI143770","article-title":"Gut-brain communication and obesity: Understanding functions of the vagus nerve","volume":"131","author":"Berthoud","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.euroneuro.2017.12.004","article-title":"The vagus nerve modulates BDNF expression and neurogenesis in the hippocampus","volume":"28","author":"Ogbonnaya","year":"2018","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s13577-019-00241-9","article-title":"Age-dependent decline in neurogenesis of the hippocampus and extracellular nucleotides","volume":"32","author":"Takei","year":"2019","journal-title":"Hum. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/j.1365-2982.2008.01104.x","article-title":"Vagal and hormonal gut-brain communication: From satiation to satisfaction","volume":"20","author":"Berthoud","year":"2008","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.biopsych.2011.07.020","article-title":"Serotonergic and noradrenergic pathways are required for the anxiolytic-like and antidepressant-like behavioral effects of repeated vagal nerve stimulation in rats","volume":"70","author":"Furmaga","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"ref_40","first-page":"272","article-title":"Enhancement of the function of rat serotonin and norepinephrine neurons by sustained vagus nerve stimulation","volume":"34","author":"Manta","year":"2009","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1111\/ejn.14368","article-title":"Hippocampal activation of 5-HT1B receptors and BDNF production by vagus nerve stimulation in rats under chronic restraint stress","volume":"50","author":"Shin","year":"2019","journal-title":"Eur. J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tins.2007.06.011","article-title":"Exercise builds brain health: Key roles of growth factor cascades and inflammation","volume":"30","author":"Cotman","year":"2007","journal-title":"Trends Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.cmet.2012.08.012","article-title":"Energy intake and exercise as determinants of brain health and vulnerability to injury and disease","volume":"16","author":"Mattson","year":"2012","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/1467-9280.t01-1-01430","article-title":"Fitness effects on the cognitive function of older adults: A meta-analytic study","volume":"14","author":"Colcombe","year":"2003","journal-title":"Psychol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1212\/WNL.0b013e318225ab66","article-title":"Does vigorous exercise have a neuroprotective effect in Parkinson disease","volume":"77","author":"Ahlskog","year":"2011","journal-title":"Neurology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"607","DOI":"10.2165\/00007256-200838070-00006","article-title":"Physical activity and epilepsy: Proven and predicted benefits","volume":"38","author":"Arida","year":"2008","journal-title":"Sports Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1212\/WNL.0b013e3182535d35","article-title":"Total daily physical activity and the risk of AD and cognitive decline in older adults","volume":"78","author":"Buchman","year":"2012","journal-title":"Neurology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S0893-133X(99)00059-7","article-title":"Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression","volume":"21","author":"Beard","year":"1999","journal-title":"Neuropsychopharmacology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuroscience.2011.12.053","article-title":"Exercise induces mitochondrial biogenesis after brain ischemia in rats","volume":"205","author":"Zhang","year":"2012","journal-title":"Neuroscience"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8680","DOI":"10.1523\/JNEUROSCI.1731-05.2005","article-title":"Exercise enhances learning and hippocampal neurogenesis in aged mice","volume":"25","author":"Shubert","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/373109a0","article-title":"Exercise and brain neurotrophins","volume":"373","author":"Neeper","year":"1995","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1111\/j.1460-9568.2004.03720.x","article-title":"Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition","volume":"20","author":"Vaynman","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.brainres.2005.11.062","article-title":"Exercise differentially regulates synaptic proteins associated to the function of BDNF","volume":"1070","author":"Vaynman","year":"2006","journal-title":"Brain Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3389\/fncel.2017.00013","article-title":"Intense Exercise Promotes Adult Hippocampal Neurogenesis But Not Spatial Discrimination","volume":"11","author":"So","year":"2017","journal-title":"Front. Cell Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","article-title":"A PGC1-\u03b1-dependent myokine that drives brown-fat-like development of white fat and thermogenesis","volume":"481","author":"Wu","year":"2012","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7671","DOI":"10.1074\/jbc.M114.617399","article-title":"SMAD3 negatively regulates serum irisin and skeletal muscle FNDC5 and peroxisome proliferator-activated receptor \u03b3 coactivator 1-\u03b1 (PGC-1\u03b1) during exercise","volume":"290","author":"Tiano","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cmet.2013.09.008","article-title":"Exercise induces hippocampal BDNF through a PGC-1\u03b1\/FNDC5 pathway","volume":"18","author":"Wrann","year":"2013","journal-title":"Cell Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/dvdy.10099","article-title":"Mouse PeP: A novel peroxisomal protein linked to myoblast differentiation and development","volume":"224","author":"Chien","year":"2002","journal-title":"Dev. Dyn."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.neuroscience.2013.02.050","article-title":"Irisin-immunoreactivity in neural and non-neural cells of the rodent","volume":"240","author":"Dun","year":"2013","journal-title":"Neuroscience"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s40279-014-0293-4","article-title":"Chronic Exercise Training and Circulating Irisin in Adults: A Meta-Analysis","volume":"45","author":"Qiu","year":"2015","journal-title":"Sports Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.cmet.2016.05.025","article-title":"Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function","volume":"24","author":"Moon","year":"2016","journal-title":"Cell Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1152\/physiolgenomics.00174.2013","article-title":"Identification of human exercise-induced myokines using secretome analysis","volume":"46","author":"Catoire","year":"2014","journal-title":"Physiol. Genom."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Hashimoto, T., Tsukamoto, H., Ando, S., and Ogoh, S. (2021). Effect of Exercise on Brain Health: The Potential Role of Lactate as a Myokine. Metabolites, 11.","DOI":"10.3390\/metabo11120813"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3233\/BPL-210133","article-title":"Muscle-to-Brain Signaling Via Myokines and Myometabolites","volume":"8","author":"Rai","year":"2022","journal-title":"Brain Plast."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1073\/pnas.1010529108","article-title":"Normal gut microbiota modulates brain development and behavior","volume":"108","author":"Wang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.bbi.2015.04.004","article-title":"Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour","volume":"48","author":"Desbonnet","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3920\/BM2011.0015","article-title":"BDNF expression in the hippocampus of maternally separated rats: Does Bifidobacterium breve 6330 alter BDNF levels","volume":"2","author":"Barrett","year":"2011","journal-title":"Benef. Microbes"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.4014\/jmb.1805.05025","article-title":"Lactobacillus johnsonii CJLJ103 Attenuates Scopolamine-Induced Memory Impairment in Mice by Increasing BDNF Expression and Inhibiting NF-\u03baB Activation","volume":"28","author":"Lee","year":"2018","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_69","first-page":"145","article-title":"Effect of the probiotic Lactobacillus plantarum IS-10506 on BDNF and 5HT stimulation: Role of intestinal microbiota on the gut-brain axis","volume":"11","author":"Ranuh","year":"2019","journal-title":"Iran J. Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.neuint.2013.10.006","article-title":"Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine","volume":"63","author":"Savignac","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/syn.21880","article-title":"Neonatal prebiotic (BGOS) supplementation increases the levels of synaptophysin, GluN2A-subunits and BDNF proteins in the adult rat hippocampus","volume":"70","author":"Williams","year":"2016","journal-title":"Synapse"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/j.1365-2982.2010.01620.x","article-title":"Reduced anxiety-like behavior and central neurochemical change in germ-free mice","volume":"23","author":"Neufeld","year":"2011","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1053\/j.gastro.2011.04.052","article-title":"The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice","volume":"141","author":"Bercik","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7801","DOI":"10.18632\/aging.103093","article-title":"Age-related shifts in gut microbiota contribute to cognitive decline in aged rats","volume":"12","author":"Li","year":"2020","journal-title":"Aging"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Distrutti, E., O\u2019Reilly, J.A., McDonald, C., Cipriani, S., Renga, B., Lynch, M.A., and Fiorucci, S. (2014). Modulation of intestinal microbiota by the probiotic VSL#3 resets brain gene expression and ameliorates the age-related deficit in LTP. PLoS ONE., 9.","DOI":"10.1371\/journal.pone.0106503"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Corpuz, H.M., Ichikawa, S., Arimura, M., Mihara, T., Kumagai, T., Mitani, T., Nakamura, S., and Katayama, S. (2018). Long-Term Diet Supplementation with Lactobacillus paracasei K71 Prevents Age-Related Cognitive Decline in Senescence-Accelerated Mouse Prone 8. Nutrients, 10.","DOI":"10.3390\/nu10060762"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Dehghani, F., Abdollahi, S., Shidfar, F., Clark, C.C.T., and Soltani, S. (2022). Probiotics supplementation and brain-derived neurotrophic factor (BDNF): A systematic review and meta-analysis of randomized controlled trials. Nutr. Neurosci., 1\u201311.","DOI":"10.1080\/1028415X.2022.2110664"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1017\/S1461145710000738","article-title":"Blood BDNF concentrations reflect brain-tissue BDNF levels across species","volume":"14","author":"Klein","year":"2011","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0165-1781(02)00005-7","article-title":"Decreased serum brain-derived neurotrophic factor levels in major depressed patients","volume":"109","author":"Karege","year":"2002","journal-title":"Psychiatry Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.jad.2011.06.041","article-title":"Correlations between brain-derived neurotrophic factor and clinical symptoms in medicated patients with major depression","volume":"135","author":"Satomura","year":"2011","journal-title":"J. Affect. Disord."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1038\/npp.2015.85","article-title":"Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors","volume":"40","author":"Hill","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1126\/science.1083328","article-title":"Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants","volume":"301","author":"Santarelli","year":"2003","journal-title":"Science"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.21037\/atm-20-5599","article-title":"Antidepressant functions of Jie Yu Chu Fan capsule in promoting hippocampal nerve cell neurogenesis in a mouse model of chronic unpredictable mild stress","volume":"8","author":"Ji","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.pnpbp.2004.11.009","article-title":"The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: A preliminary study","volume":"29","author":"Aydemir","year":"2005","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S0006-3223(03)00181-1","article-title":"Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants","volume":"54","author":"Shimizu","year":"2003","journal-title":"Biol. Psychiatry."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0091-3057(96)00169-4","article-title":"Antidepressant-like effect of brain-derived neurotrophic factor (BDNF)","volume":"56","author":"Siuciak","year":"1997","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8415","DOI":"10.1021\/acs.jafc.8b02462","article-title":"Clostridium butyricum Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behavior in Mice via the Gut-Brain Axis","volume":"66","author":"Sun","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.psyneuen.2019.02.025","article-title":"Faecalibacterium prausnitzii (ATCC 27766) has preventive and therapeutic effects on chronic unpredictable mild stress-induced depression-like and anxiety-like behavior in rats","volume":"104","author":"Hao","year":"2019","journal-title":"Psychoneuroendocrinology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jnutbio.2019.01.007","article-title":"Bifidobacterium with the role of 5-hydroxytryptophan synthesis regulation alleviates the symptom of depression and related microbiota dysbiosis","volume":"66","author":"Tian","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"416","DOI":"10.3389\/fnagi.2018.00416","article-title":"Probiotics and Prebiotics as a Therapeutic Strategy to Improve Memory in a Model of Middle-Aged Rats","volume":"10","author":"Borlongan","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jnutbio.2019.03.021","article-title":"Probiotics mixture increases butyrate, and subsequently rescues the nigral dopaminergic neurons from MPTP and rotenone-induced neurotoxicity","volume":"69","author":"Srivastav","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/gerona\/glaa090","article-title":"Probiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial","volume":"76","author":"Kim","year":"2021","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-1-4939-0897-4_5","article-title":"Vagal pathways for microbiome-brain-gut axis communication","volume":"817","author":"Forsythe","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/nn.4030","article-title":"Host microbiota constantly control maturation and function of microglia in the CNS","volume":"18","author":"Erny","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1113\/jphysiol.2004.063388","article-title":"Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice","volume":"558","author":"Sudo","year":"2004","journal-title":"J. Physiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1080\/19490976.2017.1353849","article-title":"Serum cortisol mediates the relationship between fecal Ruminococcus and brain N-acetylaspartate in the young pig","volume":"8","author":"Mudd","year":"2017","journal-title":"Gut Microbes"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nn.4476","article-title":"Interactions between the microbiota, immune and nervous systems in health and disease","volume":"20","author":"Fung","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.neuint.2016.06.011","article-title":"The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis","volume":"99","author":"Stilling","year":"2016","journal-title":"Neurochem. Int."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.2147\/IJN.S374024","article-title":"Selenium Nanoparticles-Enriched Lactobacillus casei ATCC 393 Prevents Cognitive Dysfunction in Mice Through Modulating Microbiota-Gut-Brain Axis","volume":"17","author":"Qiao","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bbr.2014.07.027","article-title":"Serotonin, tryptophan metabolism and the brain-gut-microbiome axis","volume":"277","author":"Clarke","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/nyas.13416","article-title":"Recent developments in understanding the role of the gut microbiota in brain health and disease","volume":"1420","author":"Sherwin","year":"2018","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3389\/fmed.2018.00053","article-title":"Of Microbes and Minds: A Narrative Review on the Second Brain Aging","volume":"5","author":"Calvani","year":"2018","journal-title":"Front. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"G907","DOI":"10.1152\/ajpgi.2001.281.4.G907","article-title":"Vagal afferent responses to fatty acids of different chain length in the rat","volume":"281","author":"Lal","year":"2001","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jnutbio.2018.03.009","article-title":"Short-chain fatty acids suppress food intake by activating vagal afferent neurons","volume":"57","author":"Goswami","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.tim.2021.02.001","article-title":"Microbial Regulation of Host Physiology by Short-chain Fatty Acids","volume":"29","author":"Wells","year":"2021","journal-title":"Trends Microbiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3389\/fimmu.2019.00277","article-title":"Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases","volume":"10","author":"Landskron","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s12020-018-1605-5","article-title":"Microbiota and metabolic diseases","volume":"61","author":"Pascale","year":"2018","journal-title":"Endocrine"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"973","DOI":"10.3389\/fmicb.2020.00973","article-title":"An Overview on Fecal Branched Short-Chain Fatty Acids Along Human Life and as Related With Body Mass Index: Associated Dietary and Anthropometric Factors","volume":"11","author":"Nogacka","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/jam.12415","article-title":"Summer Meeting 2013: Growth and physiology of bifidobacteria","volume":"116","author":"Moens","year":"2014","journal-title":"J. Appl. Microbiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.tim.2014.03.001","article-title":"Phylogeny, culturing, and metagenomics of the human gut microbiota","volume":"22","author":"Walker","year":"2014","journal-title":"Trends Microbiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.2174\/13816128113199990462","article-title":"Role of monocarboxylate transporters in drug delivery to the brain","volume":"20","author":"Vijay","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1194\/jlr.R067629","article-title":"Short- and medium-chain fatty acids in energy metabolism: The cellular perspective","volume":"57","author":"Wojtczak","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1136\/gut.28.10.1221","article-title":"Short chain fatty acids in human large intestine, portal, hepatic and venous blood","volume":"28","author":"Cummings","year":"1987","journal-title":"Gut"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1152\/ajplegacy.1973.224.6.1450","article-title":"Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids","volume":"224","author":"Oldendorf","year":"1973","journal-title":"Am. J. Physiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1128\/aem.62.5.1589-1592.1996","article-title":"Pathways of acetate, propionate, and butyrate formation by the human fecal microbial flora","volume":"62","author":"Miller","year":"1996","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0009-8981(79)90109-8","article-title":"Short chain fatty acids in plasma and brain: Quantitative determination by gas chromatography","volume":"92","author":"Bachmann","year":"1979","journal-title":"Clin. Chim. Acta"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"412946","DOI":"10.1155\/2015\/412946","article-title":"Neuroprotective Effects of Clostridium butyricum against Vascular Dementia in Mice via Metabolic Butyrate","volume":"2015","author":"Liu","year":"2015","journal-title":"Biomed Res. Int."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neulet.2015.12.047","article-title":"Clostridium butyricum pretreatment attenuates cerebral ischemia\/reperfusion injury in mice via anti-oxidation and anti-apoptosis","volume":"613","author":"Sun","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.neuropharm.2009.04.008","article-title":"Effects of the histone deacetylase inhibitor sodium butyrate in models of depression and anxiety","volume":"57","author":"Gundersen","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"458","DOI":"10.3109\/15622975.2011.585663","article-title":"Antidepressant-like effect of sodium butyrate (HDAC inhibitor) and its molecular mechanism of action in the rat hippocampus","volume":"13","author":"Yamawaki","year":"2012","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2174\/1567202611666140829162158","article-title":"Sodium butyrate functions as an antidepressant and improves cognition with enhanced neurotrophic expression in models of maternal deprivation and chronic mild stress","volume":"11","author":"Valvassori","year":"2014","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"pyu032","DOI":"10.1093\/ijnp\/pyu032","article-title":"Antidepressant-like effect of sodium butyrate is associated with an increase in TET1 and in 5-hydroxymethylation levels in the Bdnf gene","volume":"18","author":"Wei","year":"2014","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.12659\/MSM.902770","article-title":"Apigenin Ameliorates Post-Stroke Cognitive Deficits in Rats through Histone Acetylation-Mediated Neurochemical Alterations","volume":"23","author":"Tu","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.bbi.2003.08.002","article-title":"Brain response to cecal infection with Campylobacter jejuni: Analysis with Fos immunohistochemistry","volume":"18","author":"Gaykema","year":"2004","journal-title":"Brain Behav. Immun."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Cruz-Mendoza, F., Jauregui-Huerta, F., Aguilar-Delgadillo, A., Garc\u00eda-Estrada, J., and Luquin, S. (2022). Immediate Early Gene c-fos in the Brain: Focus on Glial Cells. Brain Sci., 12.","DOI":"10.3390\/brainsci12060687"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"16050","DOI":"10.1073\/pnas.1102999108","article-title":"Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve","volume":"108","author":"Bravo","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.neuron.2018.11.018","article-title":"Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder","volume":"101","author":"Sgritta","year":"2019","journal-title":"Neuron"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/j.1365-2982.2011.01796.x","article-title":"The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication","volume":"23","author":"Bercik","year":"2011","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.neuroimage.2010.03.004","article-title":"Age-related changes in grey and white matter structure throughout adulthood","volume":"51","author":"Giorgio","year":"2010","journal-title":"Neuroimage"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.1038\/npp.2016.126","article-title":"The Role of BDNF in Age-Dependent Changes of Excitatory and Inhibitory Synaptic Markers in the Human Prefrontal Cortex","volume":"41","author":"Oh","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nm.1912","article-title":"Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer\u2019s disease","volume":"15","author":"Nagahara","year":"2009","journal-title":"Nat. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1016\/j.neurobiolaging.2013.06.014","article-title":"Reduced neuroplasticity in aged rats: A role for the neurotrophin brain-derived neurotrophic factor","volume":"34","author":"Calabrese","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s12974-020-01887-1","article-title":"BDNF reverses aging-related microglial activation","volume":"17","author":"Wu","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molbrainres.2005.06.014","article-title":"Regional expression of brain derived neurotrophic factor (BDNF) is correlated with dynamic patterns of promoter methylation in the developing mouse forebrain","volume":"140","author":"Dennis","year":"2005","journal-title":"Brain Res. Mol. Brain Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3543\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:29:38Z","timestamp":1760120978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,10]]},"references-count":134,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043543"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043543","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,10]]}}}