Long‐term consequences of early postnatal lead exposure on hippocampal synaptic activity in adult mice

Abstract

Introduction Lead (Pb) exposure yielding blood lead levels (BLL) as low as 2 µg/dl in children is an international problem. More common in US low‐income neighborhoods, childhood Pb exposure can cause behavioral and cognitive deficits, including working memory impairments, which can persist into adulthood. So far, studies characterized short‐term effects of high Pb exposure on neuronal structure and function. However, long‐term consequences of early chronic Pb exposure on neuronal activity are poorly documented. Methods Here, we exposed male and female mice (PND [postnatal day] 0 to PND 28) to one of three Pb treatments: 0 ppm (sodium‐treated water, control), 30 ppm (low dose), and 330 ppm (high dose) lead acetate. Once the male and female mice were 9–12 months old, extracellular field recordings on hippocampal slices were performed. Results We show that at CA3 to CA1 synapses, synaptic transmission was decreased and neuronal fiber activity was increased in males exposed to lowest level Pb. In contrast, both synaptic transmission and neuronal fiber activity were increased in females exposed to high Pb. The ventral hippocampus–medial prefrontal cortex (vHPC–mPFC) synapses are crucial for working memory in rodents. The lowest level Pb decreased vHPC–mPFC synaptic transmission, whereas high Pb decreased short‐term synaptic depression. Conclusions Overall, we show for the first time that early exposure to either high or lowest level Pb has long‐term consequences on different synaptic properties of at least two hippocampal synapses. Such consequences of early Pb exposure might worsen the cognitive decline observed in aging men and women. Our results suggest that additional efforts should focus on the consequences of early Pb exposure especially in at‐risk communities.

Establishment of an a priori protocol for the implementation and interpretation of an in‐vitro testing battery for the assessment of developmental neurotoxicity

“…This is especially striking for lead(II)acetate. Lead specifically interferes with synapse development and function in vitro and in vivo (Gąssowska et al, 2016;Nam et al, 2019;Tena et al, 2019). Exposure, effects and underlying MoA are comprehensively summarized by .…”

Mitragynine (Kratom)—Withdrawal behaviour and cognitive impairments can be ameliorated by an epigenetic mechanism

“…MIT‐withdrawn rats exhibited a marked decline in I/O, PPF, and LTP in this study, suggesting a negative impact of MIT withdrawal on both short‐ and long‐term synaptic plasticity. PPF occur due to residual Ca 2+ augmenting neurotransmitter release presynaptically when two single‐stimulus pulses are applied with short interstimulus intervals ranging from 20 to 1000 ms (Tena et al, 2019). MIT's ability to suppress the PPF ratio in this study may be related to its decreased Ca 2+ influx activity (Basheer et al, 2023; Hassan et al, 2019).…”

Chronic Pb Exposure Induces Anxiety and Depression-like Behaviors in Mice via Excitatory Neuronal Hyperexcitability in Ventral Hippocampal Dentate Gyrus

“…Thus, as a potential target of Pb neurotoxicity, the hypothalamus could be an important part of the neural network involved in Pb-induced anxiety and depression. The medial prefrontal cortex (mPFC) might also participate in this neural network because the frequency of mEPSC in mPFC was decreased in a rat model of depression, while Pb exposure alters vHPC-mPFC synaptic transmission and short-term synaptic depression in adult mice. , However, there is no literature suggesting that Pb can damage the amygdala, which is also linked to anxiety and depression, , in adult animals and human. However, whether and how Pb acts on Nav channels and which set of brain regions is affected in Pb-induced anxiety and depression-like behaviors require further exploration.…”