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The mechanisms of lead neurotoxicity remain unclear, but microgliosis and astrogliosis are potential candidates, leading to an inflammatory cascade and interrupting the pathways involved in hippocampal functions. Moreover, these molecular changes can be impactful as they may contribute to the pathophysiology of behavioral deficits and cardiovascular complications observed in chronic lead exposure. Nevertheless, the health effects and the underlying influence mechanism of intermittent lead exposure in the nervous and cardiovascular systems are still vague. Thus, we used a rat model of intermittent lead exposure to determine the systemic effects of lead and on microglial and astroglial activation in the hippocampal dentate gyrus throughout time. In this study, the intermittent group was exposed to lead from the fetal period until 12 weeks of age, no exposure (tap water) until 20 weeks, and a second exposure from 20 to 28 weeks of age. A control group (without lead exposure) matched in age and sex was used. At 12, 20 and 28 weeks of age, both groups were submitted to a physiological and behavioral evaluation. Behavioral tests were performed for the assessment of anxiety-like behavior and locomotor activity (open-field test), and memory (novel object recognition test). In the physiological evaluation, in an acute experiment, blood pressure, electrocardiogram, and heart and respiratory rates were recorded, and autonomic reflexes were evaluated. The expression of GFAP, Iba-1, NeuN and Synaptophysin in the hippocampal dentate gyrus was assessed. Intermittent lead exposure induced microgliosis and astrogliosis in the hippocampus of rats and changes in behavioral and cardiovascular function. We identified increases in GFAP and Iba1 markers together with presynaptic dysfunction in the hippocampus, concomitant with behavioral changes. This type of exposure produced significant long-term memory dysfunction. Regarding physiological changes, hypertension, tachypnea, baroreceptor reflex impairment and increased chemoreceptor reflex sensitivity were observed. In conclusion, the present study demonstrated the potential of lead intermittent exposure inducing reactive astrogliosis and microgliosis, along with a presynaptic loss that was accompanied by alterations of homeostatic mechanisms. This suggests that chronic neuroinflammation promoted by intermittent lead exposure since fetal period may increase the susceptibility to adverse events in individuals with pre-existing cardiovascular disease and\/or in the elderly.<\/jats:p>","DOI":"10.3390\/cells12050818","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T02:30:45Z","timestamp":1678156245000},"page":"818","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with Neuroinflammation"],"prefix":"10.3390","volume":"12","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, 37075 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, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1679-1727","authenticated-orcid":false,"given":"Tiago F.","family":"Outeiro","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center G\u00f6ttingen, 37075 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), 37073 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"840547","DOI":"10.1155\/2014\/840547","article-title":"Pb Neurotoxicity: Neuropsychological Effects of Lead Toxicity","volume":"2014","author":"Mason","year":"2014","journal-title":"BioMed Res. 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