Low‐Level Lead Exposure in the Early Postnatal Period Results in Persisting Neuroplastic Deficits Associated with Memory Consolidation

Abstract

Prospective studies in humans and experimental investigations in animals have correlated elevated perinatal blood lead levels with enduring behavioural and cognitive perturbations. Although deficits in neuroplastic events necessary for long-term memory consolidation have been observed during the postnatal period, there is little evidence that these persist into adulthood in the absence of continued lead exposure. To address this issue, we exposed Wistar rat pups to 400 mg of PbCI,/L via their dams' drinking water from postnatal day 1 to 30. At postnatal day 80, the animals were trained in a onetrial, step-through, light-dark passive avoidance paradigm. Prior postnatal lead exposure resulted in a significant decline in recall latency on posttraining day 5, an effect that was specific to the learned response as no obvious behavioural alterations were apparent in openfield studies. As recall was unaffected in the immediate 48-h posttraining period, this suggested an enduring impairment in events associated with long-term memory storage. To investigate this further, we determined the influence of prior lead exposure on the transient modulations of hippocampal neural cell adhesion molecule polysialylation state that occur in the 10-12-h posttraining period, a neuroplastic event associated with memory consolidation. Direct quantification of polysialylated dentate neurons revealed prior lead exposure to have no effect on basal number but to significantly delay and blunt the transient increase observed in control animals at the 12-h posttraining time. These findings confirm that lead exposure in the postnatal period results in enduring neuroplastic deficits most likely associated with reordering of connections in pathways subservient to memory consolidation.

Elucidation of mechanisms underlying the protective effects of olive leaf extract against lead-induced neurotoxicity in Wistar rats

“…Evidence from animal research indi-cates that early Pb exposure causes permanent changes in the hypothalamic-pituitary axis, glucocorticoid dysregulation, and altered dopaminergic and GABA-ergic (γ-aminobutyric acid-containing) systems, which are associated with increased anxiety and decreased socializing behavior (Nieto-Fernandez et al, 2006). Moreover studies have shown that rats exposed to low levels of Pb during the first postnatal month have deficits in memory and long-term potentiation that persist in the adult age (Murphy and Regan, 1999). Finally, several studies indicate that Pb affects the activity of the monoaminergic system during development of the CNS (Devi et al, 2005, Sansar et al, 2011.…”

Neuro beneficial effects of Pimpinella anisum against lead exposure

“…Exposure to low levels of lead during early development has been implicated in long-lasting behavioural abnormalities and cognitive deficits in children and experimental animals. [2][3][4][5] The learning impairment and other behavioural disturbances like anxiety and depression that affect children and laboratory animals, suggests that the hippocampus may be one region that is adversely affected during early life. Recent developments suggest that gestation through lactation is a sensitive period, when exposure to low levels of Pb cause long-lasting cognitive deficits.…”

Low Lead Exposure During Foetal and Early Postnatal Life Impairs Passive Avoidance Learning in Adulthood in Rats

“…Jaako-Movits et al (12) found that lead exposure in suckling pups impaired contextual fear conditioning and reduced hippocampal neurogenesis as they reached adulthood. Similarly, Murphy et al (13) found deficits associated with memory consolidation in adult rats exposed to lead in the early postnatal period. Others, in contrast, found that maternal lead exposure did not impair adult rats' memory retention (14,15) and spatial learning (16).…”