Chronic Fluoride Exposure Disrupts Calcium-Dependent Neurodevelopmental Signalling and Brain Proteomic Architecture:
Ravindra Shantakumar Swamy1, Shalini Choudhary2, Abhishek Ambawatiya2
1Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal, 576 104, Karnataka, India.
Biological Trace Element Research
|August 8, 2026
Summary
Fluoride exposure during development harms neurobehavioral functions and brain molecular pathways. Naringin, a natural flavonoid, demonstrated multi-target neuroprotection, significantly counteracting these adverse effects in rats.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Long-term fluoride exposure during early development is linked to neurobehavioral deficits, oxidative stress, and molecular brain changes.
- The precise mechanisms of fluoride neurotoxicity and the protective potential of flavonoids like naringin are not fully understood.
Purpose of the Study:
- To investigate the neurodevelopmental toxicity of fluoride exposure.
- To evaluate the multi-target neuroprotective efficacy of naringin against fluoride-induced neurodevelopmental harms in a rat model.
Main Methods:
- Rats were exposed to sodium fluoride with or without naringin during development.
- Assessments included behavioral tests, biochemical analyses, oxidative stress markers, proteomic profiling (LC-MS/MS), and gene expression analysis (PCR).
Main Results:
- Fluoride exposure caused sensorimotor impairments, behavioral deficits, increased oxidative stress, and altered gene expression.
- Proteomic analysis revealed dysregulation in mitochondrial function, calcium signaling, and synaptic plasticity pathways.
- Naringin co-treatment significantly ameliorated behavioral deficits, restored antioxidant balance, and mitigated molecular pathway disruptions.
Conclusions:
- Fluoride exposure induces neurodevelopmental toxicity through oxidative imbalance, mitochondrial dysfunction, and altered signaling pathways.
- Naringin exhibits significant multi-target neuroprotective effects against fluoride-induced developmental toxicity.
- Naringin shows promise as a potential therapeutic agent against fluoride neurotoxicity.
Keywords:
AntioxidantsBehavioural toxicologyCalcium signallingFluorideMitochondrial dysfunctionNaringinNeurodevelopmentOxidative stressPCRProteomics

