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Apoptotic and Degenerative Changes in the Enteric Nervous System Following Exposure to Fluoride During Pre- and

Saba Sarwar1,2, Javed Ahsan Quadri3,4, Manoj Kumar2

  • 1Clinical Ecotoxicology (Diagnostic & Research) Facility, All India Institute of Medical Sciences, New Delhi, 110029, India.

Biological Trace Element Research
|June 29, 2020
PubMed

Insights

Fluoride exposure during pregnancy and lactation harms the developing enteric nervous system (ENS) in rat pups. This can lead to gut dysfunction and impaired growth by increasing oxidative stress and cell death.

Area of Science:

  • Neuroscience
  • Toxicology
  • Developmental Biology

Background:

  • Fluorosis endemic areas pose health risks to children, including gastrointestinal issues and growth deficits.
  • The enteric nervous system (ENS) is crucial for gut function and susceptible to toxins.
  • Prenatal and early-life exposure to environmental toxins like fluoride may impact ENS development.

Purpose of the Study:

  • To investigate the effects of maternal fluoride exposure during pregnancy and lactation on the ENS development in first-generation rat pups.
  • To assess fluoride-induced oxidative stress, cellular damage, and apoptosis in the ENS.
  • To evaluate changes in neuronal and glial markers and gut morphology.

Main Methods:

  • Pregnant rats were exposed to 0, 50, or 100 ppm fluoride in drinking water from pregnancy through lactation.
  • Pups were assessed on postnatal day 21 for fluoride levels, oxidative stress, histopathology, ultrastructure, apoptosis (TUNEL), and gene expression (ELAVL4, GFAP).
  • Immunofluorescence was used to analyze neuronal (HuC/D) and glial (GFAP) markers.

Main Results:

  • Fluoride exposure increased oxidative stress, cellular injury, and apoptosis in enteric neurons, glia, and epithelial cells of the distal colon.
  • Observed ganglionic degeneration, reduced HuC/D and GFAP expression, altered muscle layer thickness, and tissue edema in fluoride-treated groups.
  • Evidence suggests fluoride disrupts ENS development through oxidative stress and apoptosis.

Conclusions:

  • Maternal fluoride exposure during critical developmental periods (pregnancy, lactation) induces significant damage to the developing ENS in offspring.
  • Increased apoptosis of enteric neurons and glial cells may lead to reduced cell numbers and impaired ENS development.
  • These findings highlight the potential neurotoxic effects of fluoride on the developing gut, contributing to health issues in fluorosis-endemic regions.

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