Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with Neuroinflammation
The nervous system is the primary target for lead exposure and the developing brain appears to be especially susceptible, namely the hippocampus. The mechanisms of lead neurotoxicity remain unclear, but microgliosis and astrogliosis are potential candidates, leading to an inflammatory cascade and in...
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MDPI AG
2023-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/5/818 |
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| author | Liana Shvachiy Ângela Amaro-Leal Tiago F. Outeiro Isabel Rocha Vera Geraldes |
| author_facet | Liana Shvachiy Ângela Amaro-Leal Tiago F. Outeiro Isabel Rocha Vera Geraldes |
| author_sort | Liana Shvachiy |
| collection | DOAJ |
| description | The nervous system is the primary target for lead exposure and the developing brain appears to be especially susceptible, namely the hippocampus. 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. |
| first_indexed | 2024-03-11T07:28:29Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T07:28:29Z |
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| spelling | doaj.art-3b09162678e743a580e606598e8392dc2023-11-17T07:28:31ZengMDPI AGCells2073-44092023-03-0112581810.3390/cells12050818Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with NeuroinflammationLiana Shvachiy0Ângela Amaro-Leal1Tiago F. Outeiro2Isabel Rocha3Vera Geraldes4Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, 37075 Göttingen, GermanyCardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, PortugalDepartment of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, 37075 Göttingen, GermanyCardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, PortugalCardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, PortugalThe nervous system is the primary target for lead exposure and the developing brain appears to be especially susceptible, namely the hippocampus. 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.https://www.mdpi.com/2073-4409/12/5/818intermittent lead exposure toxicitylong-term memory impairmenthypertensionbaroreflex impairmentneuroinflammationsynaptic dysfunction |
| spellingShingle | Liana Shvachiy Ângela Amaro-Leal Tiago F. Outeiro Isabel Rocha Vera Geraldes Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with Neuroinflammation Cells intermittent lead exposure toxicity long-term memory impairment hypertension baroreflex impairment neuroinflammation synaptic dysfunction |
| title | Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with Neuroinflammation |
| title_full | Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with Neuroinflammation |
| title_fullStr | Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with Neuroinflammation |
| title_full_unstemmed | Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with Neuroinflammation |
| title_short | Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with Neuroinflammation |
| title_sort | intermittent lead exposure induces behavioral and cardiovascular alterations associated with neuroinflammation |
| topic | intermittent lead exposure toxicity long-term memory impairment hypertension baroreflex impairment neuroinflammation synaptic dysfunction |
| url | https://www.mdpi.com/2073-4409/12/5/818 |
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