Dataset Information

Lead Exposure During Development Alters Synaptic Organization and Protein Expression in Rat Hippocampus

ABSTRACT: Lead (Pb) is a potent neurotoxin with disastrous effects on cognition, memory, and sensory functions. Pb exposure during the developmental stage of life causes irreversible changes in neuronal morphology impacting the physiological functions from reduced motor skills and lowered intelligence quotient to developmental disorders and delayed puberty. To investigate the effect of developmental Pb exposure on the rodent hippocampus, we exposed rat pups to 100 ppm lead acetate via lactation and looked into the morphological and proteomic alterations in the hippocampal neurons. Our Nissl stain data revealed a significant reduction in the number of CA1 neurons in the hippocampus of the Pb-exposed rats. Further, we analyzed the dendritic tree morphology of the CA1 neurons and reported neuronal hypertrophy and a reduction in spine density in both the basal and the apical dendrites in Pb-exposed rats. Our mass spectrometric data identified a total of 6780 proteins out of which 190 proteins were p-value significant. We reported a total of 31 dysregulated proteins in the hippocampus of Pb-exposed rats. The changes seen in the protein expression profile and reduction in neuronal numbers in addition to the altered dendritic tree of Pb-exposed neurons suggest the molecular and morphological changes that could underlie the memory and cognitive deficits seen in Pb-exposed animals.

INSTRUMENT(S):

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain, Hippocampal Formation

SUBMITTER: Bhupesh Mehta

LAB HEAD: Bhupesh Mehta

PROVIDER: PXD064482 | Pride | 2025-12-01

REPOSITORIES: Pride

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Lead exposure during development alters synaptic organization and protein expression in rat hippocampus.

Shirke Omkar O Velu Sneha S Pandita Satyarth S Saha Amit Kumar AK Patil Rahul Ravindranath RR Joshi Neha S NS Govindaraj Periyasamy P Rao Laxmi T LT Markandeya Yogananda S YS Mehta Bhupesh B

Journal of hazardous materials 20251122

Lead (Pb) is a well-established environmental neurotoxicant known to impair cognitive, sensory, and behavioral functions. Developmental exposure to Pb induces irreversible morphological and functional alterations in the central nervous system. In this study, we investigated the impact of early-life Pb exposure on anxiety-like behaviour, hippocampal structure and protein expression in rats. Neonatal rats were exposed to 100 ppm Lead acetate via maternal lactation from postnatal day (PND) 1-21. Be ...[more]

PMID: 41297250

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Project description:Exposure to lead (Pb) during childhood can result in learning disabilities and behavioral problems. Although described in animal models, whether Pb exposure also alters neuronal differentiation in the developing brains of exposed children is unknown. Here, we investigated the effects of physiologically relevant concentrations of Pb (from 0.4 to 1.9 M-BM-5M or 0 to 40M-BM-5g/dl) on the capacity of human embryonic stem cells (hESCs) to progress to a neuronal fate. We found that neither acute nor chronic exposure to Pb prevented hESCs from generating neural precursor cells (NPCs). NPCs derived from hESCs chronically exposed to 1.9 M-BM-5M or 40M-BM-5g/dl Pb throughout the neural differentiation process generated 2.5 times more TUJ1-positive neurons than those derived from control hESCs. Pb exposure of hESCs during the stage of neural rosette formation resulted in a significant decrease in the expression levels of the neural marker genes PAX6 and MSI1. Furthermore, the resulting NPCs differentiated into neurons with shorter neurites and less branching than control neurons, as assessed by Sholl analysis. DNA methylation studies of control, acutely treated hESCs and NPCs derived from chronically exposed hESCs using the Illumina HumanMethylation450 BeadChipM-BM-. demonstrated that Pb exposure induced changes in the methylation status of genes involved in neurogenetic signaling pathways. In summary, our study shows that exposure to Pb subtly alters the neuronal differentiation of exposed hESCs and that these changes could be partly mediated by modifications in the DNA methylation status of genes crucial to brain development. We analyzed the methylation profile of undifferentiated (n=2 independent experiments) and differentiating (n=2 independent experiments) human embryonic stem cells (hESCs) acutely exposed to losed to lead (Pb) and neural precursor cells derived from hESCs chronically exposed to Pb throughout the neural differentiation process (n=3 independent experiments).

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	BM_Lead_F10_R1.mzML	Mzml
	BM_Lead_F10_R1.raw	Raw
	BM_Lead_F10_R2.mzML	Mzml
	BM_Lead_F10_R2.raw	Raw
	BM_Lead_F10_R3.mzML	Mzml