{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T22:05:56Z","timestamp":1771797956586,"version":"3.50.1"},"reference-count":85,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology (FCT)","doi-asserted-by":"publisher","award":["SFRH\/BD\/143286\/2019"],"award-info":[{"award-number":["SFRH\/BD\/143286\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology (FCT)","doi-asserted-by":"publisher","award":["SFRH\/BPD\/119315\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/119315\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology (FCT)","doi-asserted-by":"publisher","award":["EXC 2067\/1- 390729940"],"award-info":[{"award-number":["EXC 2067\/1- 390729940"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology (FCT)","doi-asserted-by":"publisher","award":["SFB1286 (B8)"],"award-info":[{"award-number":["SFB1286 (B8)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["SFRH\/BD\/143286\/2019"],"award-info":[{"award-number":["SFRH\/BD\/143286\/2019"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["SFRH\/BPD\/119315\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/119315\/2016"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["EXC 2067\/1- 390729940"],"award-info":[{"award-number":["EXC 2067\/1- 390729940"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["SFB1286 (B8)"],"award-info":[{"award-number":["SFB1286 (B8)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Lead is a heavy metal whose widespread use has resulted in environmental contamination and significant health problems, particularly if the exposure occurs during developmental stages. It is a cumulative toxicant that affects multiple systems of the body, including the cardiovascular and nervous systems. Chronic lead exposure has been defined as a cause of behavioral changes, inflammation, hypertension, and autonomic dysfunction. However, different environmental lead exposure paradigms can occur, and the different effects of these have not been described in a broad comparative study. In the present study, rats of both sexes were exposed to water containing lead acetate (0.2% w\/v), from the fetal period until adulthood. Developmental Pb-exposed (DevPb) pups were exposed to lead until 12 weeks of age (n = 13); intermittent Pb exposure (IntPb) pups drank leaded water until 12 weeks of age, tap water until 20 weeks, and leaded water for a second time from 20 to 28 weeks of age (n = 14); and the permanent (PerPb) exposure group were exposed to lead until 28 weeks of age (n = 14). A control group (without exposure, Ctrl), matched in age and sex was used. After exposure protocols, at 28 weeks of age, behavioral tests were performed for assessment of anxiety (elevated plus maze test), locomotor activity (open-field test), and memory (novel object recognition test). Metabolic parameters were evaluated for 24 h, and the acute experiment was carried out. Blood pressure (BP), electrocardiogram, and heart (HR) and respiratory (RF) rates were recorded. Baroreflex gain, chemoreflex sensitivity, and sympathovagal balance were calculated. Immunohistochemistry protocol for NeuN, Syn, Iba-1, and GFAP staining was performed. All Pb-exposed groups showed hypertension, concomitant with a decrease in baroreflex gain and chemoreceptor hypersensitivity, without significant changes in HR and RF. Long-term memory impairment associated with reactive astrogliosis and microgliosis in the dentate gyrus of the hippocampus, indicating the presence of neuroinflammation, was also observed. However, these alterations seemed to reverse after lead abstinence for a certain period (DevPb) and were enhanced when a second exposure occurred (IntPb), along with a synaptic loss. These results suggest that the duration of Pb exposure is more relevant than the timing of exposure, since the PerPb group presented more pronounced effects and a significant increase in the LF and HF bands and anxiety levels. In summary, this is the first study with the characterization and comparison of physiological, autonomic, behavioral, and molecular changes caused by different low-level environmental lead exposures, from the fetal period to adulthood, where the duration of exposure was the main factor for stronger adverse effects. These kinds of studies are of immense importance, showing the importance of the surrounding environment in health from childhood until adulthood, leading to the creation of new policies for toxicant usage control.<\/jats:p>","DOI":"10.3390\/biology11081164","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T20:52:01Z","timestamp":1659559921000},"page":"1164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["From Molecular to Functional Effects of Different Environmental Lead Exposure Paradigms"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4576-0017","authenticated-orcid":false,"given":"Liana","family":"Shvachiy","sequence":"first","affiliation":[{"name":"Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center G\u00f6ttingen, 37073 G\u00f6ttingen, Germany"},{"name":"Cardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, Portugal"},{"name":"Institute of Physiology, Faculty of Medicine of the University of Lisbon, 1649-035 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-6372","authenticated-orcid":false,"given":"\u00c2ngela","family":"Amaro-Leal","sequence":"additional","affiliation":[{"name":"Cardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, Portugal"},{"name":"Institute of Physiology, Faculty of Medicine of the University of Lisbon, 1649-035 Lisbon, Portugal"}]},{"given":"Tiago F.","family":"Outeiro","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center G\u00f6ttingen, 37073 G\u00f6ttingen, Germany"},{"name":"Max Planck Institute for Natural Science, 37075 G\u00f6ttingen, Germany"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle Upon Tyne NE2 4HH, UK"},{"name":"Scientific Employee with an Honorary Contract at Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 37075 G\u00f6ttingen, Germany"}]},{"given":"Isabel","family":"Rocha","sequence":"additional","affiliation":[{"name":"Cardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, Portugal"},{"name":"Institute of Physiology, Faculty of Medicine of the University of Lisbon, 1649-035 Lisbon, Portugal"}]},{"given":"Vera","family":"Geraldes","sequence":"additional","affiliation":[{"name":"Cardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, Portugal"},{"name":"Institute of Physiology, Faculty of Medicine of the University of Lisbon, 1649-035 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"ref_1","unstructured":"(2022, May 24). 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