{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:08:56Z","timestamp":1785820136966,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research (MUR)","award":["PRIN 2022PZH8SX"],"award-info":[{"award-number":["PRIN 2022PZH8SX"]}]},{"name":"Italian Ministry of University and Research (MUR)","award":["PRIN PNRR P2022JRBMB"],"award-info":[{"award-number":["PRIN PNRR P2022JRBMB"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Activity-dependent neuroprotective protein (ADNP) is a neuroprotective protein essential for embryonic development, proper brain development, and neuronal plasticity. Its mutation causes the autism-like ADNP syndrome (also called the Helsmoortel-Van der Aa syndrome), characterized by neural developmental disorders and motor dysfunctions. Similar to the ADNP syndrome, the ADNP haploinsufficient mouse shows low synapse density, leading to motor and cognitive ability delays. Moderate physical activity (PA) has several neuroprotective and cognitive benefits, promoting neuronal survival, differentiation, neurogenesis, and plasticity. Until now, no study has investigated the effect of moderate exercise on ADNP expression and distribution in the rat brain. The aim of the current investigation was to study the effects of moderate exercise on the ADNP expression and neuronal activation measured by the microtubule protein \u03b2-Tubulin III. In pursuit of this objective, twenty-four rats were selected and evenly distributed into two categories: sedentary control rats and rats exposed to moderate physical activity on a treadmill over a span of 12 weeks. Our results showed that moderate PA increases the expression of ADNP and \u03b2-Tubulin III in the dentate gyrus (DG) hippocampal region and cerebellum. Moreover, we found a co-localization of ADNP and \u03b2-Tubulin III in both DG and cerebellum, suggesting a direct association of ADNP with adult neuronal activation induced by moderate PA.<\/jats:p>","DOI":"10.3390\/ijms25084382","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T08:41:06Z","timestamp":1713256866000},"page":"4382","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Moderate Physical Activity Increases the Expression of ADNP in Rat Brain"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0173-4885","authenticated-orcid":false,"given":"Grazia","family":"Maugeri","sequence":"first","affiliation":[{"name":"Section of Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, University of Catania, 95100 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata Grazia","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0160-9040","authenticated-orcid":false,"given":"Concetta","family":"Federico","sequence":"additional","affiliation":[{"name":"Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7568-5823","authenticated-orcid":false,"given":"Salvatore","family":"Saccone","sequence":"additional","affiliation":[{"name":"Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1114-8265","authenticated-orcid":false,"given":"Velia","family":"D\u2019Agata","sequence":"additional","affiliation":[{"name":"Section of Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, University of Catania, 95100 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8260-8890","authenticated-orcid":false,"given":"Giuseppe","family":"Musumeci","sequence":"additional","affiliation":[{"name":"Section of Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, University of Catania, 95100 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1600-0838.2006.00520.x","article-title":"Evidence for prescribing exercise as therapy in chronic disease","volume":"16","author":"Pedersen","year":"2006","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e04315","DOI":"10.1016\/j.heliyon.2020.e04315","article-title":"The impact of physical activity on psychological health during COVID-19 pandemic in Italy","volume":"6","author":"Maugeri","year":"2020","journal-title":"Heliyon"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Maugeri, G., and D\u2019Agata, V. (2020). Effects of Physical Activity on Amyotrophic Lateral Sclerosis. J. Funct. Morphol. Kinesiol., 5.","DOI":"10.3390\/jfmk5020029"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Maugeri, G., and Musumeci, G. (2021). Adapted Physical Activity to Ensure the Physical and Psychological Well-Being of COVID-19 Patients. J. Funct. Morphol. Kinesiol., 6.","DOI":"10.3390\/jfmk6010013"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zangh\u00ec, M., Petrigna, L., Maugeri, G., D\u2019Agata, V., and Musumeci, G. (2022). The Practice of Physical Activity on Psychological, Mental, Physical, and Social Wellbeing for Breast-Cancer Survivors: An Umbrella Review. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph191610391"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3233\/BPL-180069","article-title":"The Neuroprotective Effects of Exercise: Maintaining a Healthy Brain Throughout Aging","volume":"4","author":"Vecchio","year":"2018","journal-title":"Brain Plast."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Festa, F., Medori, S., and Macr\u00ec, M. (2023). Move Your Body, Boost Your Brain: The Positive Impact of Physical Activity on Cognition across All Age Groups. Biomedicines, 11.","DOI":"10.3390\/biomedicines11061765"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jpsychires.2014.10.003","article-title":"A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor","volume":"60","author":"Szuhany","year":"2015","journal-title":"J. Psychiatr. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1093\/gerona\/glu136","article-title":"Moderate-intensity physical activity, hippocampal volume, and memory in older adults with mild cognitive impairment","volume":"70","author":"Makizako","year":"2015","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/hipo.22397","article-title":"Low-intensity daily walking activity is associated with hippocampal volume in older adults","volume":"25","author":"Varma","year":"2015","journal-title":"Hippocampus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/6368","article-title":"Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus","volume":"2","author":"Kempermann","year":"1999","journal-title":"Nat. Neurosci."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.neulet.2013.01.005","article-title":"Voluntary resistance running induces increased hippocampal neurogenesis in rats comparable to load-free running","volume":"537","author":"Lee","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5638","DOI":"10.1073\/pnas.0611721104","article-title":"An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus","volume":"104","author":"Pereira","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"112481","DOI":"10.1016\/j.bbr.2020.112481","article-title":"Moderate intensity intermittent exercise upregulates neurotrophic and neuroprotective genes expression and inhibits Purkinje cell loss in the cerebellum of ovariectomized rats","volume":"382","author":"Rauf","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S147","DOI":"10.5213\/inj.1836226.113","article-title":"Treadmill Exercise Improves Motor Function by Suppressing Purkinje Cell Loss in Parkinson Disease Rats","volume":"22","author":"Lee","year":"2018","journal-title":"Int. Neurourol. J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Di Liegro, C.M., Schiera, G., Proia, P., and Di Liegro, I. (2019). Physical Activity and Brain Health. Genes, 10.","DOI":"10.3390\/genes10090720"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1046\/j.1471-4159.1999.0721283.x","article-title":"Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide","volume":"72","author":"Bassan","year":"1999","journal-title":"J. Neurochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1074\/jbc.M007416200","article-title":"Cloning and characterization of the human activity-dependent neuroprotective protein","volume":"276","author":"Zamostiano","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Maugeri, G., D\u2019Amico, A.G., Magr\u00ec, B., Musumeci, G., and D\u2019Agata, V. (2022). Activity-Dependent Neuroprotective Protein (ADNP): An Overview of Its Role in the Eye. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113654"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0165-3806(03)00162-7","article-title":"Activity-dependent neuroprotective protein: A novel gene essential for brain formation","volume":"144","author":"Pinhasov","year":"2003","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1136\/bjophthalmol-2014-305359","article-title":"A brief review of Boston type-1 and osteo-odonto keratoprostheses","volume":"99","author":"Avadhanam","year":"2015","journal-title":"Br. J. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e501","DOI":"10.1038\/tp.2014.138","article-title":"Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer\u2019s pathologies","volume":"5","author":"Malishkevich","year":"2015","journal-title":"Transl. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1385\/JMN:24:2:181","article-title":"Brain injury-dependent expression of activity-dependent neuroprotective protein","volume":"24","author":"Zaltzman","year":"2004","journal-title":"J. Mol. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1038\/s41380-019-0563-5","article-title":"Discovery of autism\/intellectual disability somatic mutations in Alzheimer\u2019s brains: Mutated ADNP cytoskeletal impairments and repair as a case study","volume":"26","author":"Hadar","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1124\/jpet.107.129551","article-title":"Activity-dependent neuroprotective protein snippet NAP reduces tau hyperphosphorylation and enhances learning in a novel transgenic mouse model","volume":"323","author":"Pinhasov","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1002\/jnr.23808","article-title":"Sexual divergence in activity-dependent neuroprotective protein impacting autism, schizophrenia, and Alzheimer\u2019s disease","volume":"95","author":"Gozes","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/s41598-018-36859-2","article-title":"Cellular and animal models of skin alterations in the autism-related ADNP syndrome","volume":"9","author":"Mollinedo","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_29","first-page":"309","article-title":"Expression of activity-dependent neuroprotective protein in the brain of adult rats","volume":"23","author":"Gennet","year":"2008","journal-title":"Histol. Histopathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/cm.10116","article-title":"Class III beta-tubulin in human development and cancer","volume":"55","author":"Katsetos","year":"2003","journal-title":"Cell Motil. Cytoskeleton"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1083\/jcb.100.3.764","article-title":"A polymer-dependent increase in phosphorylation of beta-tubulin accompanies differentiation of a mouse neuroblastoma cell line","volume":"100","author":"Gard","year":"1985","journal-title":"J. Cell Biol."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.neuroscience.2015.06.027","article-title":"Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers","volume":"301","author":"Moreira","year":"2015","journal-title":"Neuroscience"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3389\/fpsyg.2012.00086","article-title":"The effects of aerobic activity on brain structure","volume":"3","author":"Thomas","year":"2012","journal-title":"Front. Psychol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Duly, A.M.P., Kao, F.C.L., Teo, W.S., and Kavallaris, M. (2022). \u03b2III-Tubulin Gene Regulation in Health and Disease. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.851542"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1016\/j.celrep.2018.07.029","article-title":"Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration","volume":"24","author":"Latremoliere","year":"2018","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.cell.2009.12.011","article-title":"Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance","volume":"140","author":"Tischfield","year":"2010","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4275","DOI":"10.1038\/s41467-020-18046-y","article-title":"Steps towards standardized quantification of adult neurogenesis","volume":"11","author":"Zhao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.cell.2016.10.021","article-title":"Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior","volume":"167","author":"Schafer","year":"2016","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.tics.2019.01.006","article-title":"Exercise and Hippocampal Memory Systems","volume":"23","author":"Voss","year":"2019","journal-title":"Trends Cogn. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6137","DOI":"10.1038\/s41598-017-06150-x","article-title":"Neurogenesis from Sox2 expressing cells in the adult cerebellar cortex","volume":"7","author":"Ahlfeld","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Leal-Galicia, P., Ch\u00e1vez-Hern\u00e1ndez, M.E., Mata, F., Mata-Lu\u00e9vanos, J., Rodr\u00edguez-Serrano, L.M., Tapia-de-Jes\u00fas, A., and Buenrostro-J\u00e1uregui, M.H. (2021). Adult Neurogenesis: A Story Ranging from Controversial New Neurogenic Areas and Human Adult Neurogenesis to Molecular Regulation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111489"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1038\/mp.2015.208","article-title":"Sexual divergence in microtubule function: The novel intranasal microtubule targeting SKIP normalizes axonal transport and enhances memory","volume":"21","author":"Amram","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/mp.2013.174","article-title":"Autophagy has a key role in the pathophysiology of schizophrenia","volume":"20","author":"Malishkevich","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/s41398-020-00904-4","article-title":"Tauopathy in the young autistic brain: Novel biomarker and therapeutic target","volume":"10","author":"Grigg","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13148-023-01450-8","article-title":"Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism","volume":"15","author":"Konings","year":"2023","journal-title":"Clin. Epigenet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1017\/S1740925X05000013","article-title":"Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes","volume":"1","author":"Furman","year":"2004","journal-title":"Neuron Glia Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ganaiem, M., Karmon, G., Ivashko-Pachima, Y., and Gozes, I. (2022). Distinct Impairments Characterizing Different ADNP Mutants Reveal Aberrant Cytoplasmic-Nuclear Crosstalk. Cells, 11.","DOI":"10.3390\/cells11192994"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s12031-007-9013-y","article-title":"ADNP differential nucleus\/cytoplasm localization in neurons suggests multiple roles in neuronal differentiation and maintenance","volume":"35","author":"Mandel","year":"2008","journal-title":"J. Mol. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kapitansky, O., Sragovich, S., Jaljuli, I., Hadar, A., Giladi, E., and Gozes, I. (2020). Age and Sex-Dependent ADNP Regulation of Muscle Gene Expression Is Correlated with Motor Behavior: Possible Feedback Mechanism with PACAP. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186715"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s11357-019-00079-x","article-title":"ADNP differentially interact with genes\/proteins in correlation with aging: A novel marker for muscle aging","volume":"41","author":"Kapitansky","year":"2019","journal-title":"Geroscience"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Di Rosa, M., Castrogiovanni, P., Trovato, F.M., Malatino, L., Ravalli, S., Imbesi, R., Szychlinska, M.A., and Musumeci, G. (2019). Adapted Moderate Training Exercise Decreases the Expression of Ngal in the Rat Kidney: An Immunohistochemical Study. Appl. Sci., 9.","DOI":"10.3390\/app9061041"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"10097","DOI":"10.1002\/jcb.28293","article-title":"PACAP through EGFR transactivation preserves human corneal endothelial integrity","volume":"120","author":"Maugeri","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.tiv.2017.07.003","article-title":"Nicotine promotes blood retinal barrier damage in a model of human diabetic macular edema","volume":"44","author":"Maugeri","year":"2017","journal-title":"Toxicol. In Vitro"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"101978","DOI":"10.1016\/j.npep.2019.101978","article-title":"Protective effect of PACAP against ultraviolet B radiation-induced human corneal endothelial cell injury","volume":"79","author":"Maugeri","year":"2020","journal-title":"Neuropeptides"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4382\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:28:37Z","timestamp":1760106517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,16]]},"references-count":55,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25084382"],"URL":"https:\/\/doi.org\/10.3390\/ijms25084382","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,16]]}}}