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Effects of Gestational and Lactational Lead Exposure and High Fat Diet Feeding on Cerebellar Development of Postnatal
Jin Seok Seo1, Shin Hyo Lee2, Hyung-Sun Won2
1Department of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
Insights
Combined exposure to lead (Pb) and a high-fat diet (HFD) during pregnancy and lactation severely damages developing rat cerebellums. This co-administration impairs crucial neuronal cells, synapses, and myelination, exacerbating oxidative stress and inflammation.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Obesity and lead (Pb) exposure negatively impact adult brain function and plasticity.
- The combined effects of Pb and high-fat diet (HFD) on the developing cerebellum are not well understood.
Purpose of the Study:
- To investigate the impact of Pb exposure and HFD on cerebellar development in rat offspring.
Main Methods:
- Rats were fed a chow diet (CD) or HFD, with Pb administered to HFD-fed females before and during gestation and lactation.
- Cerebellar tissues and blood were analyzed on postnatal day 21.
- Histological and immunohistochemical analyses assessed neuronal integrity, synaptic structures, myelination, oxidative stress, and inflammation.
Main Results:
- Co-administration of Pb and HFD significantly increased blood Pb levels and Purkinje cell degeneration.
- Pb and HFD reduced calbindin-28Kd-, GAD67-, NMDAR1-, and PSD95-immunopositive cells and pinceau structures.
- Myelinated axonal fibers were damaged, and oxidative stress and pro-inflammatory responses were exacerbated.
Conclusions:
- Maternal HFD and Pb exposure during gestation and lactation are detrimental to cerebellar development in offspring.
- Combined exposure leads to significant structural and molecular damage in the developing cerebellum.
- The findings highlight the critical vulnerability of the developing brain to combined environmental insults.
Abstract:
Obesity and heavy metals, such as lead (Pb), are detrimental to the adult brain because they impair cognitive function and structural plasticity. However, the effects of co-administration of Pb and a high-fat diet (HFD) on the developing cerebellum is not clearly elucidated. We investigated the effects of Pb exposure (0.3% lead acetate) on developing cerebellum in the pups of an HFD-fed obese rat model. One week before mating, we fed a chow diet (CD) or HFD to the rats for one week and additionally administered Pb to HFD-fed female SD rats. Thereafter, treatment with Pb and a HFD was continued during the gestational and lactational periods. On postnatal day 21, the pups were euthanized to sample the brain tissue and blood for further analysis. Blood Pb levels were significantly higher in HFD-fed rats than in CD-fed rats. Histologically, the prominent degeneration of Purkinje cells was induced by the co-administration of Pb and HFD. The calbindin-28Kd-, GAD67-, NMDAR1-, and PSD95-immunopositive Purkinje cells and inhibitory synapse-forming pinceau structures were significantly decreased following Pb and HFD co-administration. MBP-immunoreactive myelinated axonal fibers were also impaired by HFD but were significantly damaged by the co-administration of HFD and Pb. Oxidative stress-related Nrf2-HO1 signaling was activated by HFD feeding, and Pb exposure further aggravated oxidative stress, as demonstrated by the consumption of endogenous anti-oxidant in HFD-Pb rats. The pro-inflammatory response was also increased by the co-administration of HFD and Pb in the cerebellum of the rat offspring. The present results suggest that HFD and Pb treatment during the gestational and lactational periods are harmful to cerebellar development.
