Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with Neuroinflammation

Abstract

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.

Gender-Specific Effects on the Cardiorespiratory System and Neurotoxicity of Intermittent and Permanent Low-Level Lead Exposures

“…Hypertension has been extensively documented in the scientific literature as one of the main health effects of lead exposure [23,24,[79][80][81]. However, in this study, compared to our previous results, we do not observe a concomitant baroreceptor reflex impairment, regardless of the type of exposure or gender [21,32,48,62,[82][83][84]. This lack of effect strikes a great interest, as the baroreceptor reflex is one of the main mechanisms regulating blood pressure, controlled by the higher autonomic brain regions, namely PVN-NTS axis and has been greatly characterized as one of the main autonomic effects in the presence of lead [81,[85][86][87][88][89].…”

“…Lead exposure has far-reaching health consequences, affecting multiple body systems due to its accumulation in the soft tissues [2,[5][6][7][8][9]11,[15][16][17][18][19], primarily influencing the cardiovascular and neurological systems. Long-term lead exposure has been related to cardiovascular issues such as hypertension and an increased risk of heart disease [20][21][22][23][24]. Furthermore, the neurological repercussions are especially troubling, since lead exposure has been linked to cognitive deficits, developmental delays, and behavioural abnormalities, particularly in children [25][26][27][28][29][30][31][32].…”

“…Globalisation has created new issues in the management of lead exposure [21,48]. Importing items from nations with relaxed lead-content restrictions poses a substantial danger.…”

Protective role of Eugenol against the destructive effects of lead on conditioned fear memory in male rats with post-traumatic stress disorder-related behavioral traits

“…Investigating the Effects of Lead on Memory Impairment in Post-Traumatic Stress Disorder: The prevalence of industrial and vehicular pollution has led to the introduction of certain scarce substances, such as lead, into the body, which exert unfavorable effects on the physiological system and organs of the body ( Shvachiy et al, 2023 ). Lead has been found to have a detrimental effect on the central nervous system ( Antonio et al, 2003 ).…”

Function of Glial Cells in Neuroinflammatory and Neuroimmunological Responses II

“…Lead exposure is considered one of the causes of neurological disabilities in both children and adults [ 3 ]. The study by Liana Shvachiy et al aimed to understand the molecular changes involved in the temporal remodeling of physiological functions during intermittent lead exposure [ 4 ]. They demonstrated that lead exposure in animals caused the inflammatory activation of microglia and astrocytes in the hippocampus with concomitant local neuroinflammation, consistent with changes in the reflex regulation of cardiovascular and respiratory parameters.…”