Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway
Open accessAbstract
Exercise can improve cognitive function and has been linked to the increased expression of brain-derived neurotrophic factor (BDNF). However, the underlying molecular mechanisms driving the elevation of this neurotrophin remain unknown. Here we show that FNDC5, a previously identified muscle protein that is induced in exercise and is cleaved and secreted as irisin, is also elevated by endurance exercise in the hippocampus of mice. Neuronal Fndc5 gene expression is regulated by PGC-1α, and Pgc1a(-/-) mice show reduced Fndc5 expression in the brain. Forced expression of FNDC5 in primary cortical neurons increases Bdnf expression, whereas RNAi-mediated knockdown of FNDC5 reduces Bdnf. Importantly, peripheral delivery of FNDC5 to the liver via adenoviral vectors, resulting in elevated blood irisin, induces expression of Bdnf and other neuroprotective genes in the hippocampus. Taken together, our findings link endurance exercise and the important metabolic mediators, PGC-1α and FNDC5, with BDNF expression in the brain.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
FNDC5 crosses the blood-brain barrier, inducing BDNF expression in the hippocampus, and BDNF plays a role in neurogenesis and reward-related learning and motivation.
“FNDC5 cross the blood–brain barrier inducing BDNF expression in the hippocampus, in this way BDNF plays a role in neurogenesis and reward-related learning and motivation [238].”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [238]
The Results section reports that peripheral FNDC5 delivery increased hippocampal Bdnf expression in mice. The Discussion says this suggests a circulating form crosses the blood–brain barrier; it does not establish crossing directly. The Introduction links BDNF to learning and brain development, but the passages do not support the more specific attribution of reward-related learning and motivation or a direct BDNF role in neurogenesis. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDuring exercise, peripheral muscle-secreted proteins such as cathepsin B and FNDC5/irisin cross the blood brain barrier to mediate BDNF expression in the hippocampus and subsequent neurogenesis and memory improvement.
“Furthermore, during exercise, proteins and their metabolic derivatives secreted from peripheral muscles, such as cathepsin B and FNDC5/irisin, also cross the blood brain barrier to mediate BDNF expression in the hippocampus and subsequent neurogenesis and memory improvement (Wrann et al., 2013; Moon et al., 2016).”
From Exercise-Mediated Neurogenesis in the Hippocampus via BDNF (2018) · cites this paper as Wrann et al., 2013
The Results section reports that peripheral FNDC5 delivery raised circulating irisin and hippocampal Bdnf expression in mice. The Discussion suggests that a circulating form crosses the blood–brain barrier, but says its identity remains uncertain; it does not establish that FNDC5/irisin subsequently causes neurogenesis or memory improvement. The paper does not address cathepsin B, which the citing sentence also cites Moon et al. for. (LLM, conf=0.88)
Experimental — accuracy not yet measuredStudies using aged animal models have verified that elevating the levels of circulating osteocalcin, GDF11, and FNDC5 is associated with an augmentation in BDNF levels and enhancement of neurogenesis.
“Studies using aged animal models have verified that elevating the levels of circulating OCN, GDF11, and FNDC5 is associated with an augmentation in BDNF levels and enhancement of neurogenesis.380–382”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [382]
Exercises increase transcription of PGC1α, which in complex with estrogen-related receptor alpha can stimulate expression of FNDC5 in the brain.
“In addition, exercises increase transcription of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), a protein that regulates mitochondrial biogenesis, which, in complex with estrogen-related receptor alpha, can stimulate the expression of myokine, the fibronectin type III domain-containing protein 5 (FNDC5) in the brain [187].”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [187]
Physical activity may be neuroprotective by activating the PGC1a/FNDC5/BDNF/ERK1/2 pathway.
“Data were also presented which indicate that physical activity may be neuroprotective by activating the PGC1a/FNDC5/BDNF/ERK1/2 pathway [187,188].”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [187]
Evidence is accumulating that factors released from non-neuronal tissue and delivered to the brain via the vasculature may have important roles in synaptic plasticity, memory function and mood regulation.
“Evidence is now accumulating that factors released from non-neuronal tissue148–152 and delivered via the vasculature to the brain might have important roles in synaptic plasticity, memory function and mood regulation150.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [152]
In mice, increasing intrinsic irisin expression in neurons or increasing plasma irisin elevates hippocampal Bdnf gene expression.
“For instance, in mice, increasing intrinsic irisin expression in neurons or increasing plasma levels of irisin elevates hippocampal Bdnf gene expression152.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [152]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., Rasbach, K. A., Boström, E. A., Choi, J. H., Long, J. Z., et al. (2012) · Nature · doi:10.1038/nature10777 · Cited by 4,810 · see citing works
Self-citationda Luz, A. C. D. D. S., Dias, G. P., Bevilaqua, M. C. D. N., Cocks, G. D., Gardino, P. F., Thuret, S., & Nardi, A. E. (2013) · Neuropsychobiology · doi:10.1159/000353269 · Cited by 4,012 · see citing works
Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00035-7 · Cited by 3,888 · see citing works
A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864 · see citing works
Self-citationFitness Effects on the Cognitive Function of Older Adults: A Meta-Analytic Study
Colcombe, S., & Kramer, A. F. (2003) · Psychological Science · doi:10.1111/1467-9280.t01-1-01430 · Cited by 3,782 · see citing works
Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human
Wu, J., Boström, P., Sparks, L. M., Li, Y., Choi, J. H., Giang, A.-H., Khandekar, M. J., Virtanen, K. A., Nuutila, P., Schaart, G., et al. (2012) · Cell · doi:10.1016/j.cell.2012.05.016 · Cited by 3,299 · see citing works
Self-citationExercise builds brain health: key roles of growth factor cascades and inflammation
Cotman, C. W., Berchtold, N. C., & Christie, L.-A. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.06.011 · Cited by 2,268 · see citing works
St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., Handschin, C., Zheng, K., Lin, J., Yang, W., et al. (2006) · Cell · doi:10.1016/j.cell.2006.09.024 · Cited by 2,233 · see citing works
Self-citationNeurotrophin regulation of neural circuit development and function
Park, H., & Poo, M.-M. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3379 · Cited by 2,060 · see citing works
Induction of c-fos-like protein in spinal cord neurons following sensory stimulation
Hunt, S. P., Pini, A., & Evan, G. I. (1987) · Nature · doi:10.1038/328632a0 · Cited by 1,986 · see citing works
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C. R., Granner, D. K., et al. (2001) · Nature · doi:10.1038/35093050 · Cited by 1,821 · see citing works
Self-citationHippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition
Vaynman, S., Ying, Z., & Gomez‐Pinilla, F. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03720.x · Cited by 1,460 · see citing works
CREB regulates hepatic gluconeogenesis through the coactivator PGC-1
Herzig, S., Long, F., Jhala, U. S., Hedrick, S., Quinn, R., Bauer, A., Rudolph, D., Schutz, G., Yoon, C., Puigserver, P., et al. (2001) · Nature · doi:10.1038/35093131 · Cited by 1,440 · see citing works
Self-citationPGC-1 coactivators: inducible regulators of energy metabolism in health and disease
Finck, B. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27794 · Cited by 1,427 · see citing works
Lyford, G. L., Yamagata, K., Kaufmann, W. E., Barnes, C. A., Sanders, L. K., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Lanahan, A. A., & Worley, P. F. (1995) · Neuron · doi:10.1016/0896-6273(95)90299-6 · Cited by 1,212 · see citing works
Defects in Adaptive Energy Metabolism with CNS-Linked Hyperactivity in PGC-1α Null Mice
Lin, J., Wu, P.-H., Tarr, P. T., Lindenberg, K. S., St-Pierre, J., Zhang, C.-Y., Mootha, V. K., Jäger, S., Vianna, C. R., Reznick, R. M., et al. (2004) · Cell · doi:10.1016/j.cell.2004.09.013 · Cited by 1,162 · see citing works
Self-citationHIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α
Arany, Z., Foo, S.-Y., Ma, Y., Ruas, J. L., Bommi-Reddy, A., Girnun, G., Cooper, M., Laznik, D., Chinsomboon, J., Rangwala, S. M., et al. (2008) · Nature · doi:10.1038/nature06613 · Cited by 1,054 · see citing works
Self-citationHariri, A. R., Goldberg, T. E., Mattay, V. S., Kolachana, B. S., Callicott, J. H., Egan, M. F., & Weinberger, D. R. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-17-06690.2003 · Cited by 1,045 · see citing works
Huh, J. Y., Panagiotou, G., Mougios, V., Brinkoetter, M., Vamvini, M. T., Schneider, B. E., & Mantzoros, C. S. (2012) · Metabolism · doi:10.1016/j.metabol.2012.09.002 · Cited by 1,040 · see citing works
Identification of a new class of steroid hormone receptors
Giguère, V., Yang, N., Segui, P., & Evans, R. M. (1988) · Nature · doi:10.1038/331091a0 · Cited by 867 · see citing works
Wang, J., Zhuang, J., Iyer, S., Lin, X.-Y., Whitfield, T. W., Greven, M. C., Pierce, B. G., Dong, X., Kundaje, A. B., Cheng, Y., et al. (2012) · Genome Research · doi:10.1101/gr.139105.112 · Cited by 820 · see citing works
Total daily physical activity and the risk of AD and cognitive decline in older adults
Buchman, A. S., Boyle, P. A., Yu, L., Shah, R. C., Wilson, R. S., & Bennett, D. A. (2012) · Neurology · doi:10.1212/wnl.0b013e3182535d35 · Cited by 730 · see citing works
Handschin, C., Rhee, J., Lin, J., Tarr, P. T., & Spiegelman, B. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1232352100 · Cited by 729 · see citing works
Self-citationMootha, V. K., Handschin, C., Arlow, D., Xie, X., St. Pierre, J., Sihag, S., Yang, W., Altshuler, D., Puigserver, P., Patterson, N., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401401101 · Cited by 688 · see citing works
Self-citationSchreiber, S., Emter, R., Hock, M. B., Knutti, D., Cardenas, J., Podvinec, M., Oakeley, E. J., & Kralli, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308686101 · Cited by 657 · see citing works
Activity-dependent regulation of inhibitory synapse development by Npas4
Lin, Y., Bloodgood, B. L., Hauser, J. L., Lapan, A. D., Koon, A. C., Kim, T.-K., Hu, L. S., Malik, A. N., & Greenberg, M. E. (2008) · Nature · doi:10.1038/nature07319 · Cited by 639 · see citing works
Self-citationNew Insights in the Biology of BDNF Synthesis and Release: Implications in CNS Function
Greenberg, M. E., Xu, B., Lu, B., & Hempstead, B. L. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3566-09.2009 · Cited by 597 · see citing works
Self-citationDing, Q., Vaynman, S., Akhavan, M., Ying, Z., & Gomez-Pinilla, F. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.02.084 · Cited by 555 · see citing works
Light Pulses that Shift Rhythms Induce Gene Expressions in the Suprachiasmatic Nucleus
Rusak, B., Robertson, H. A., Wisden, W., & Hunt, S. P. (1990) · Science · doi:10.1126/science.2112267 · Cited by 548 · see citing works
Neuronal Activity-Regulated Gene Transcription in Synapse Development and Cognitive Function
West, A. E., & Greenberg, M. E. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005744 · Cited by 532 · see citing works
Self-citationTapley, P. M., Lamballe, F., & Barbacid, M. (1992) · PubMed · Cited by 497 · see citing works
Eadie, B. D., Redila, V. A., & Christie, B. R. (2005) · Journal of Comparative Neurology · doi:10.1002/cne.20493 · Cited by 466 · see citing works
Does vigorous exercise have a neuroprotective effect in Parkinson disease?
Ahlskog, J. E. (2011) · Neurology · doi:10.1212/wnl.0b013e318225ab66 · Cited by 463 · see citing works
Energy intake and exercise as determinants of brain health and vulnerability to injury and disease
Mattson, M. P. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.012 · Cited by 434 · see citing works
Exercise, Antidepressant Medications, and Enhanced Brain Derived Neurotrophic Factor Expression
Russo-Neustadt, A. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00059-7 · Cited by 411 · see citing works
Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines
Cheng, A., Wan, R., Yang, J.-L., Kamimura, N., Son, T. G., Ouyang, X., Luo, Y., Okun, E., & Mattson, M. P. (2012) · Nature Communications · doi:10.1038/ncomms2238 · Cited by 401 · see citing works
Running is the neurogenic and neurotrophic stimulus in environmental enrichment
Kobilo, T., Liu, Q.-R., Gandhi, K., Mughal, M., Shaham, Y., & van Praag, H. (2011) · Learning & Memory · doi:10.1101/lm.2283011 · Cited by 385 · see citing works
Convulsant-induced increase in transcription factor messenger RNAs in rat brain.
Saffen, D. W., Cole, A. J., Worley, P. F., et al. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.20.7795 · Cited by 378 · see citing works
Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor α.
Luo, J., Sladek, R., Carrier, J., Bader, J.-A., Richard, D., & Giguère, V. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.7947-7956.2003 · Cited by 370 · see citing works
Exercise training increases mitochondrial biogenesis in the brain
Steiner, J. L., Murphy, E. A., McClellan, J. L., Carmichael, M. D., & Davis, J. M. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00343.2011 · Cited by 357 · see citing works
Bartlett, W., & Banker, G. (1984) · Journal of Neuroscience · doi:10.1523/jneurosci.04-08-01944.1984 · Cited by 348 · see citing works
Shan, T., Liang, X., Bi, P., & Kuang, S. (2013) · The FASEB Journal · doi:10.1096/fj.12-225755 · Cited by 301 · see citing works
Npas4 Regulates a Transcriptional Program in CA3 Required for Contextual Memory Formation
Ramamoorthi, K., Fropf, R., Belfort, G. M., Fitzmaurice, H. L., McKinney, R. M., Neve, R. L., Otto, T., & Lin, Y. (2011) · Science · doi:10.1126/science.1208049 · Cited by 295 · see citing works
Exercise differentially regulates synaptic proteins associated to the function of BDNF
Vaynman, S. S., Ying, Z., Yin, D., & Gomez-Pinilla, F. (2006) · Brain Research · doi:10.1016/j.brainres.2005.11.062 · Cited by 248 · see citing works
Irisin-immunoreactivity in neural and non-neural cells of the rodent
Dun, S. L., Lyu, R., Chen, Y., Chang, J. K., Luo, J. J., & Dun, N. J. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.02.050 · Cited by 236 · see citing works
Kuipers, S. D., & Bramham, C. R. (2006) · PubMed · Cited by 209 · see citing works
Lecker, S. H., Zavin, A., Cao, P., Arena, R. A., Allsup, K., Daniels, K. M., Joseph, J., Schulze, P. C., & Forman, D. E. (2012) · Circulation Heart Failure · doi:10.1161/circheartfailure.112.969543 · Cited by 197 · see citing works
Transcriptional control of mitochondrial energy metabolism through the PGC1 coactivators
Spiegelman, B. M. (2007) · Novartis Foundation Symposia · doi:10.1002/9780470725207.ch5 · Cited by 187 · cited 4× · see citing works
“ERRa Is a Key Interacting Transcription Factor with PGC-1a for Regulating Fndc5 Gene Expression in Neurons PGC-1a is a transcriptional coactivator, meaning it does not bind to the DNA itself but interacts with transcription factors to execute its effects on gene expression (Spiegelman, 2007).”
BackgroundInfluentialSelf-citationFrcp1 and Frcp2, two novel fibronectin type III repeat containing genes
Teufel, A., Malik, N., Mukhopadhyay, M., & Westphal, H. (2002) · Gene · doi:10.1016/s0378-1119(02)00828-4 · Cited by 183 · see citing works
Mouse PeP: A novel peroxisomal protein linked to myoblast differentiation and development
Ferrer-Martı́nez, A., Ruiz‐Lozano, P., & Chien, K. R. (2002) · Developmental Dynamics · doi:10.1002/dvdy.10099 · Cited by 169 · see citing works
Laganière, J., Tremblay, G. B., Dufour, C. R., Giroux, S., Rousseau, F., & Giguère, V. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313543200 · Cited by 162 · see citing works
Fndc5 knockdown significantly decreased neural differentiation rate of mouse embryonic stem cells
Hashemi, M. ‐., Ghaedi, K., Salamian, A., Karbalaie, K., Emadi‐Baygi, M., Tanhaei, S., Nasr‐Esfahani, M. H., & Baharvand, H. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.11.041 · Cited by 143 · see citing works
The homeobox protein Prox1 is a negative modulator of ERRα/PGC-1α bioenergetic functionsPreprint
Charest-Marcotte, A., Dufour, C. R., Wilson, B. J., Tremblay, A., Eichner, L. J., Arlow, D. H., Mootha, V. K., & Giguère, V. (2010) · Genes & Development · doi:10.1101/gad.1871610 · Cited by 142 · see citing works
Physical Activity and Epilepsy
Arida, R. M., Cavalheiro, É. A., da Silva, A. C., & Scorza, F. A. (2008) · Sports Medicine · doi:10.2165/00007256-200838070-00006 · Cited by 132 · see citing works
Evolutionary aspects of human exercise—Born to run purposefully
Mattson, M. P. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.01.007 · Cited by 123 · see citing works
Exercise induces mitochondrial biogenesis after brain ischemia in rats
Zhang, Q., Wu, Y., Zhang, P., Sha, H., Jia, J., Hu, Y., & Zhu, J. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2011.12.053 · Cited by 121 · see citing works
Separation of the gluconeogenic and mitochondrial functions of PGC-1α through S6 kinasePreprint
Lustig, Y., Ruas, J. L., Estall, J. L., Lo, J. C., Devarakonda, S., Laznik, D., Choi, J. H., Ono, H., Olsen, J. V., & Spiegelman, B. M. (2011) · Genes & Development · doi:10.1101/gad.2054711 · Cited by 115 · see citing works
Self-citationGarcia, C., Chen, M. J., Garza, A. A., Cotman, C. W., & Russo‐Neustadt, A. A. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00192-1 · Cited by 109 · see citing works
Parvalbumin Deficiency and GABAergic Dysfunction in Mice Lacking PGC-1α
Lucas, E. K., Markwardt, S. J., Gupta, S., Meador‐Woodruff, J. H., Lin, J. D., Overstreet‐Wadiche, L., & Cowell, R. M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0698-10.2010 · Cited by 104 · see citing works
Self-citationMa, D., Li, S., Lucas, E. K., Cowell, R. M., & Lin, J. D. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.151688 · Cited by 73 · see citing works
Self-citationPGC-1α Negatively Regulates Extrasynaptic NMDAR Activity and Excitotoxicity
Puddifoot, C. A., Martel, M., Soriano, F. X., Camacho‐Morales, A., Vidal‐Puig, A., Wyllie, D. J. A., & Hardingham, G. E. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6407-11.2012 · Cited by 63 · see citing works
Relationship between Exercise Capacity and Brain Size in Mammals
Raichlen, D. A., & Gordon, A. D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020601 · Cited by 51 · see citing works
Ostadsharif, M., Ghaedi, K., Nasr‐Esfahani, M. H., Mojbafan, M., Tanhaie, S., Karbalaie, K., & Baharvand, H. (2010) · Differentiation · doi:10.1016/j.diff.2010.11.003 · Cited by 46 · see citing works
Regulation of PGC-1α and PGC-1α-responsive genes with forskolin-induced Schwann cell differentiation
Cowell, R. M., Blake, K. R., Inoue, T., & Russell, J. W. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.04.104 · Cited by 17 · see citing works
Giménez-Cassina, A., Lim, F., & Díaz‐Nido, J. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.10.046 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Muscle–Organ Crosstalk: The Emerging Roles of Myokines
Severinsen, M. C. K., & Pedersen, B. K. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa016 · Cited by 1,226 · see citing works
“The PGC-1α-dependent myokine irisin, known for its browning effects (101), may also be involved in mediating effects of physical activity on the brain (98).”
BackgroundIntegrative Biology of Exercise
Hawley, J. A., Hargreaves, M., Joyner, M. J., & Zierath, J. R. (2014) · Cell · doi:10.1016/j.cell.2014.10.029 · Cited by 1,152 · see citing works
Colucci-D’Amato, L., Speranza, L., & Volpicelli, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207777 · Cited by 991 · see citing works
Rao, R. R., Long, J. Z., White, J. P., Svensson, K. J., Lou, J., Lokurkar, I., Jedrychowski, M. P., Ruas, J. L., Wrann, C. D., Lo, J. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.065 · Cited by 973 · see citing works
Self-citationExercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models
Lourenco, M. V., Frozza, R. L., de Freitas, G. B., Zhang, H., Kincheski, G. C., Ribeiro, F. C., Gonçalves, R. A., Clarke, J. R., Beckman, D., Staniszewski, A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0275-4 · Cited by 935 · see citing works
Basso, J. C., & Suzuki, W. A. (2016) · Brain Plasticity · doi:10.3233/bpl-160040 · Cited by 911 · see citing works
Exerkines in health, resilience and disease
Chow, L. S., Gerszten, R. E., Taylor, J. M., Pedersen, B. K., van Praag, H., Trappe, S., Febbraio, M. A., Galis, Z. S., Gao, Y., Haus, J. M., et al. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00641-2 · Cited by 927 · see citing works
Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans
Lee, P., Linderman, J. D., Smith, S., Brychta, R. J., Wang, J., Idelson, C., Perron, R. M., Werner, C. D., Phan, G. Q., Kammula, U. S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.017 · Cited by 802 · see citing works
Physical activity and muscle-brain crosstalk
Pedersen, B. K. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0174-x · Cited by 772 · see citing works
Brain metabolism in health, aging, and neurodegeneration
Camandola, S., & Mattson, M. P. (2017) · The EMBO Journal · doi:10.15252/embj.201695810 · Cited by 752 · see citing works
Agudelo, L. Z., Femenía, T., Orhan, F., Porsmyr-Palmertz, M., Goiny, M., Martinez-Redondo, V., Correia, J. C., Izadi, M., Bhat, M., Schuppe-Koistinen, I., et al. (2014) · Cell · doi:10.1016/j.cell.2014.07.051 · Cited by 739 · see citing works
Ruegsegger, G. N., & Booth, F. W. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029694 · Cited by 690 · see citing works
Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors
Kim, H., Wrann, C. D., Jedrychowski, M., Vidoni, S., Kitase, Y., Nagano, K., Zhou, C., Chou, J., Parkman, V.-J. A., Novick, S. J., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.025 · Cited by 638 · see citing works
Self-citationIntermittent metabolic switching, neuroplasticity and brain health
Mattson, M. P., Moehl, K., Ghena, N., Schmaedick, M., & Cheng, A. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.156 · Cited by 624 · see citing works
Physiology and role of irisin in glucose homeostasis
Perakakis, N., Triantafyllou, G. A., Fernández-Real, J. M., Huh, J. Y., Park, K. H., Seufert, J., & Mantzoros, C. S. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.221 · Cited by 621 · see citing works
BDNF mediates adaptive brain and body responses to energetic challenges
Marosi, K., & Mattson, M. P. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.10.006 · Cited by 568 · see citing works
Exercise-Mediated Neurogenesis in the Hippocampus via BDNF
Liu, P. Z., & Nusslock, R. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00052 · Cited by 533 · see citing works
BDNF as a Promising Therapeutic Agent in Parkinson’s Disease
Palasz, E., Wysocka, A., Gasiorowska, A., Chalimoniuk, M., Niewiadomski, W., & Niewiadomska, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031170 · Cited by 504 · see citing works
Exercise plasma boosts memory and dampens brain inflammation via clusterin
De Miguel, Z., Khoury, N., Betley, M. J., Lehallier, B., Willoughby, D., Olsson, N., Yang, A. C., Hahn, O., Lu, N., Vest, R. T., et al. (2021) · Nature · doi:10.1038/s41586-021-04183-x · Cited by 422 · see citing works
Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise
Schnyder, S., & Handschin, C. (2015) · Bone · doi:10.1016/j.bone.2015.02.008 · Cited by 419 · see citing works
Exercise hormone irisin is a critical regulator of cognitive function
Islam, M. R., Valaris, S., Young, M. F., Haley, E. B., Luo, R., Bond, S. F., Mazuera, S., Kitchen, R. R., Caldarone, B. J., Bettio, L. E. B., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00438-z · Cited by 403 · see citing works
Self-citationSkeletal Muscle as an Endocrine Organ: The Role of Myokines in Exercise Adaptations
Hoffmann, C., & Weigert, C. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029793 · Cited by 393 · see citing works
Exercise benefits on Alzheimer’s disease: State-of-the-science
Valenzuela, P. L., Castillo-García, A., Morales, J. S., de la Villa, P., Hampel, H., Emanuele, E., Lista, S., & Lucia, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101108 · Cited by 337 · see citing works
Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling
Phillips, C., Baktir, M. A., Srivatsan, M., & Salehi, A. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00170 · Cited by 330 · see citing works
Can physical exercise in old age improve memory and hippocampal function?
Duzel, E., van Praag, H., & Sendtner, M. (2016) · Brain · doi:10.1093/brain/awv407 · Cited by 329 · see citing works
Muscle as a paracrine and endocrine organ
Giudice, J., & Taylor, J. M. (2017) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.05.005 · Cited by 331 · see citing works
Huh, J. Y., Dincer, F., Mesfum, E., & Mantzoros, C. S. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.42 · Cited by 309 · see citing works
Gonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278 · see citing works
“Irisin Ob: ↑ [39]+; T2DM: ↓ [39]+ AE: ↑ (aerobic or resistance) [40]+ CE: ↓? (aerobic or resistance) [41]+ ↑ (via PGC-1α): cold-induced shivering [42], ↑AMP:ATP ratio (via AMPK-PGC-1α pathway), FGF21* [43], and METRNL (via ↑PGC-1α4)* [44] ↓: proinflammatory cytokines [45] (possibly via NF-kB-mediated inhibition of PGC…”
BackgroundInter-organ cross-talk in metabolic syndrome
Priest, C., & Tontonoz, P. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0145-5 · Cited by 279 · see citing works
Walsh, J. J., & Tschakovsky, M. E. (2018) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2018-0192 · Cited by 256 · see citing works
Marosi, K., Kim, S. W., Moehl, K., Scheibye‐Knudsen, M., Cheng, A., Cutler, R., Camandola, S., & Mattson, M. P. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13868 · Cited by 242 · see citing works
Progress and Challenges in the Biology of FNDC5 and Irisin
Maak, S., Norheim, F., Drevon, C. A., & Erickson, H. P. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab003 · Cited by 247 · see citing works
The role of exercise-induced myokines in regulating metabolism
Huh, J. Y. (2018) · Archives of Pharmacal Research · doi:10.1007/s12272-017-0994-y · Cited by 242 · see citing works
Jamwal, S., Blackburn, J. K., & Elsworth, J. D. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107705 · Cited by 236 · see citing works
Lactate and BDNF: Key Mediators of Exercise Induced Neuroplasticity?
Müller, P., Duderstadt, Y., Lessmann, V., & Müller, N. G. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9041136 · Cited by 241 · see citing works
Exercise and Hippocampal Memory Systems
Voss, M. W., Soto, C., Yoo, S., Sodoma, M., Vivar, C., & van Praag, H. (2019) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2019.01.006 · Cited by 235 · see citing works
Resistance exercise induces a greater irisin response than endurance exercise
Tsuchiya, Y., Ando, D., Takamatsu, K., & Goto, K. (2015) · Metabolism · doi:10.1016/j.metabol.2015.05.010 · Cited by 207 · see citing works
Systemic factors as mediators of brain homeostasis, ageing and neurodegeneration
Pluvinage, J. V., & Wyss-Coray, T. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0255-9 · Cited by 191 · see citing works
FNDC5/Irisin: Physiology and Pathophysiology
Waseem, R., Shamsi, A., Mohammad, T., Hassan, M. I., Kazim, S. N., Chaudhary, A. A., Rudayni, H. A., Al-Zharani, M., Ahmad, F., & Islam, A. (2022) · Molecules · doi:10.3390/molecules27031118 · Cited by 180 · see citing works
Tsuchiya, Y., Ando, D., Goto, K., Kiuchi, M., Yamakita, M., & Koyama, K. (2014) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.233.135 · Cited by 176 · see citing works
Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI
Broadhouse, K. M., Singh, M. F., Suo, C., Gates, N., Wen, W., Brodaty, H., Jain, N., Wilson, G. C., Meiklejohn, J., Singh, N., et al. (2020) · NeuroImage: Clinical · doi:10.1016/j.nicl.2020.102182 · Cited by 172 · see citing works
Irisin as a muscle-derived hormone stimulating thermogenesis – A critical update
Hofmann, T., Elbelt, U., & Stengel, A. (2014) · Peptides · doi:10.1016/j.peptides.2014.01.016 · Cited by 162 · see citing works
Myokines mediate the cross talk between skeletal muscle and other organs
Chen, W., Wang, L., You, W., & Shan, T. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30033 · Cited by 162 · see citing works
Blood-to-brain communication in aging and rejuvenation
Bieri, G., Schroer, A. B., & Villeda, S. A. (2023) · Nature Neuroscience · doi:10.1038/s41593-022-01238-8 · Cited by 156 · see citing works
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
Zhang, M., Jia, J., Yang, Y., Zhang, L., & Wang, X. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102116 · Cited by 157 · see citing works
“Long-term regular exercise has a positive effect on stimulating brain plasticity and improving cognition and brain function (Wrann et al., 2013; Ashpole et al., 2015).”
BackgroundKatsouri, L., Lim, Y. M., Blondrath, K., Eleftheriadou, I., Lombardero, L., Birch, A. M., Mirzaei, N., Irvine, E. E., Mazarakis, N. D., & Sastre, M. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1606171113 · Cited by 146 · see citing works
KIM, H.-J., LEE, H.-J., SO, B., SON, J. S., YOON, D., & SONG, W. (2016) · Physiological Research · doi:10.33549/physiolres.932997 · Cited by 141 · see citing works
Ruiz-Ariza, A., Grao-Cruces, A., de Loureiro, N. E. M., & Martínez-López, E. J. (2017) · International Review of Sport and Exercise Psychology · doi:10.1080/1750984x.2016.1184699 · Cited by 140 · see citing works
Amelioration of pathologic α-synuclein-induced Parkinson’s disease by irisin
Kam, T.-I., Park, H., Chou, S.-C., Van Vranken, J. G., Mittenbühler, M. J., Kim, H., A, M., Choi, Y. R., Biswas, D., Wang, J., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2204835119 · Cited by 125 · see citing works
Self-citationLi, J. W., O’Connor, H., O’Dwyer, N., & Orr, R. (2017) · Journal of Science and Medicine in Sport · doi:10.1016/j.jsams.2016.11.025 · Cited by 125 · see citing works
G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy
White, J. P., Wrann, C. D., Rao, R. R., Nair, S. K., Jedrychowski, M. P., You, J.-S., Martínez-Redondo, V., Gygi, S. P., Ruas, J. L., Hornberger, T. A., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417898111 · Cited by 123 · see citing works
Self-citationProtective actions of exercise-related FNDC5/irisin in memory and Alzheimer's disease
de Freitas, G. B., Lourenco, M. V., & De Felice, F. G. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15039 · Cited by 120 · see citing works
Molecular mechanisms of brain-derived neurotrophic factor in neuro-protection: Recent developments
Zhao, H., Alam, A., San, C.-Y., Eguchi, S., Chen, Q., Lian, Q., & Ma, D. (2017) · Brain Research · doi:10.1016/j.brainres.2017.03.029 · Cited by 122 · see citing works
Sleep, circadian biology and skeletal muscle interactions: Implications for metabolic health
Morrison, M., Halson, S. L., Weakley, J., & Hawley, J. A. (2022) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2022.101700 · Cited by 118 · see citing works
Gamas, L., Matafome, P., & Seiça, R. (2015) · Journal of Diabetes Research · doi:10.1155/2015/359159 · Cited by 114 · see citing works
Kerling, A., Kück, M., Tegtbur, U., Grams, L., Weber-Spickschen, S., Hanke, A., Stubbs, B., & Kahl, K. G. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.03.034 · Cited by 113 · see citing works
Shen, Y., Ye, B., Chen, P., Wang, Q., Fan, C., Shu, Y., & Xiang, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00394 · Cited by 105 · see citing works
Neuroprotective effects of dietary restriction: Evidence and mechanisms
Pani, G. (2015) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2015.03.004 · Cited by 103 · see citing works
Does PGC1α/FNDC5/BDNF Elicit the Beneficial Effects of Exercise on Neurodegenerative Disorders?
Jodeiri Farshbaf, M., Ghaedi, K., Megraw, T. L., Curtiss, J., Shirani Faradonbeh, M., Vaziri, P., & Nasr-Esfahani, M. H. (2016) · NeuroMolecular Medicine · doi:10.1007/s12017-015-8370-x · Cited by 101 · see citing works
Irisin, an exercise-induced bioactive peptide beneficial for health promotion during aging process
Zhang, H., Wu, X., Liang, J., Kirberger, M., & Chen, N. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101680 · Cited by 88 · see citing works
Numakawa, T., Richards, M., Nakajima, S., Adachi, N., Furuta, M., Odaka, H., & Kunugi, H. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00136 · Cited by 86 · see citing works
Can exercise training teach us how to treat Alzheimer's disease?
Huuha, A. M., Norevik, C. S., Moreira, J. B. N., Kobro-Flatmoen, A., Scrimgeour, N., Kivipelto, M., Van Praag, H., Ziaei, M., Sando, S. B., Wisløff, U., et al. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101559 · Cited by 79 · see citing works
Physical Exercise-Induced Myokines in Neurodegenerative Diseases
Lee, B., Shin, M., Park, Y., Won, S.-Y., & Cho, K. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115795 · Cited by 79 · see citing works
Nicolini, C., Michalski, B., Toepp, S. L., Turco, C. V., D'Hoine, T., Harasym, D., Gibala, M. J., Fahnestock, M., & Nelson, A. J. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.03.042 · Cited by 69 · see citing works
Fuller, O. K., Whitham, M., Mathivanan, S., & Febbraio, M. A. (2020) · Cells · doi:10.3390/cells9102182 · Cited by 60 · see citing works
Central inhibitory effects on feeding induced by the adipo-myokine irisin
Ferrante, C., Orlando, G., Recinella, L., Leone, S., Chiavaroli, A., Di Nisio, C., Shohreh, R., Manippa, F., Ricciuti, A., Vacca, M., et al. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.09.011 · Cited by 62 · see citing works
Dethlefsen, M. M., Halling, J. F., Møller, H. D., Plomgaard, P., Regenberg, B., Ringholm, S., & Pilegaard, H. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.07.011 · Cited by 54 · see citing works
(2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.012 · Cited by 46 · see citing works
Reparaz-Escudero, I., Izquierdo, M., Bischoff-Ferrari, H. A., Martínez-Lage, P., & Sáez de Asteasu, M. L. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102463 · Cited by 45 · see citing works
Sadighparvar, S., Darband, S. G., Yousefi, B., Kaviani, M., Ghaderi‐Pakdel, F., Mihanfar, A., Babaei, G., Mobaraki, K., & Majidinia, M. (2020) · Experimental Physiology · doi:10.1113/ep088605 · Cited by 41 · see citing works
Irisin enhances longevity by boosting SIRT1, AMPK, autophagy and telomerase
Sánchez, B., Muñoz-Pinto, M. F., & Cano, M. (2023) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2022.41 · Cited by 38 · see citing works
The Potential Role of Irisin in Vascular Function and Atherosclerosis: A Review
Byun, K., & Lee, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197184 · Cited by 38 · see citing works
Lei, Z., Mozaffaritabar, S., Kawamura, T., Koike, A., Kolonics, A., Kéringer, J., Pinho, R. A., Sun, J., Shangguan, R., & Radák, Z. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e24421 · Cited by 36 · see citing works
Sun, H., Gao, X., Que, X., Liu, L., Ma, J., He, S., Gao, Q., & Wang, T. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.11.034 · Cited by 33 · see citing works
Zhan, G., Huang, N., Li, S., Hua, D., Zhang, J., Fang, X., Yang, N., Luo, A., & Yang, C. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5041-2 · Cited by 32 · see citing works
Irisin increases the expression of anorexigenic and neurotrophic genes in mouse brain
Natalicchio, A., Marrano, N., Biondi, G., Dipaola, L., Spagnuolo, R., Cignarelli, A., Perrini, S., Laviola, L., & Giorgino, F. (2020) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3238 · Cited by 31 · see citing works
Pyrżak, B., Demkow, U., & Kucharska, A. M. (2015) · Advances in experimental medicine and biology · doi:10.1007/5584_2015_149 · Cited by 26 · see citing works
Chbeir, S., & Carrión, V. (2023) · World Journal of Psychiatry · doi:10.5498/wjp.v13.i5.144 · Cited by 25 · see citing works
Leardini-Tristao, M., Charles, A.-L., Lejay, A., Pizzimenti, M., Meyer, A., Estato, V., Tibiriçá, E., Andres, E., & Geny, B. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8050653 · Cited by 17 · see citing works
“For example, an exercise-related increase in irisin resulted in BDNF expression in the hippocampus [59] and Küster et al.”
BackgroundSuzuki, W. A. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.022 · Cited by 17 · see citing works
Study on the comorbid mechanisms of sarcopenia and late-life depression
Wu, J., Tang, J., Huang, D., Wang, Y., Zhou, E., Ru, Q., Xu, G., Chen, L., & Wu, Y. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115538 · Cited by 12 · see citing works
Self-citationWang, N., Zhu, S., Chen, S., Zou, J., Zeng, P., & Tan, S. (2025) · Reviews in the Neurosciences · doi:10.1515/revneuro-2024-0147 · Cited by 12 · see citing works
- Authors
- Wrann, C. D., White, J. P., Salogiannnis, J., Laznik-Bogoslavski, D., Wu, J., Ma, D., Lin, J. D., Greenberg, M. E., & Spiegelman, B. M.
- Affiliations
- Harvard University (US)
- University of Michigan (US)
- Corresponding author
- Greenberg, Michael E.
- Spiegelman, Bruce M.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 18
- Issue
- 5
- Pages
- 649-659
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3980968
- OpenAlex
- W2147515151
- Cited by
- 1,440
- References
- 65
- Citations by year
- 2026: 175 · 2025: 168 · 2024: 140 · 2023: 147 · 2022: 145 · 2021: 135 · 2020: 127 · 2019: 105 · 2018: 74 · 2017: 72 · 2016: 55 · 2015: 47 · 2014: 43 · 2013: 6
- FWCI
- 24.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK031405, DK-31405, RC4DK090861, DK90861, R01DK054477, R37DK031405, P30DK020572)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- physical activity, brain-derived neurotrophic factor, FNDC5, irisin, PGC-1α, hippocampus, endurance exercise, cognitive function, neuroprotection, adenoviral vector, cortical neurons
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, ERRalpha Estrogen-Related Receptor, Adenoviridae, Animals, Fibronectins, Genetic Vectors, Hippocampus, Humans, Male, Mice, Inbred C57BL, Neurons, Physical Conditioning, Animal, Protein Binding, Receptors, Estrogen, Recombinant Proteins, Transcription Factors, Signal Transduction, Gene Expression Regulation, Developmental, Brain-Derived Neurotrophic Factor, Gene Expression Profiling, Feedback, Physiological, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
