Biology subjects

Sunkara, S.

Publications and source records attributed to Sunkara, S..

3 recordsLinked to original sources

bioRxiv2026

Time-dependent effect of fluoride on caries lesions development in a rat caries model

Since model dose-response is critical when assessing caries lesion development over time, this study evaluated the influence of fluoride dose and treatment duration on caries progression in a rat caries model. Streptococcus mutans-infected Sprague-Dawley rats were treated with deionized water, 226 ppm F-, or 2,260 ppm F- twice daily for 3, 4, or 5 weeks. Caries lesions were assessed using Larson's modification of the Keyes scoring system and complemented by micro-computed tomography (microCT). Intraoral fluoride availability, serum and bone fluoride concentrations and microbial counts were also determined. Fluoride reduced caries severity in a dose- and time-dependent manner. While early enamel lesions were detected in all groups, extensive dentine lesions increased over time, in a dose-dependent manner, in the control and 226 ppm F- groups, and were not observed in the 2,260 ppm F- group after 5 weeks. Intraoral and bone fluoride availability increased significantly with fluoride concentration and treatment duration, whereas serum fluoride levels reflected fluoride dose instead of treatment duration. MicroCT-derived enamel volume correlated negatively with both total and extensive caries scores, supporting its utility as an objective measure of lesion severity. In conclusion, extending model length from 3 to 5 weeks increased the severity of caries lesions in a dose-dependent manner. Fluoride intraoral availability and bone fluoride also demonstrated a dose and time-dependent response.

pathology↗

bioRxiv2025

Amyloid beta aggregation promoted by iron leads to neuronal loss in an ex vivo model of Alzheimer's disease

Alzheimers disease (AD) is a progressive neurodegenerative disorder characterized by amyloid beta (A{beta}) plaques and neurofibrillary tangles. Despite well-established iron accumulation in the AD brain, its role in exacerbating A{beta} toxicity is often overlooked in therapeutic research. We developed a 3D ex vivo organotypic brain slice cultures (OBSC) with A{beta} monomers and ferric citrate to mimic A{beta} deposits and iron overload to investigate the impact of excess iron on A{beta} toxicity in pig and human brains. Light and electron microscopy, biochemical assays, and multiple regression modeling were employed to assess iron-mediated A{beta} toxicity in neurons and glial cells. We show that OBSC offer a close approximation of in vivo morphological and physiological properties and can retain both neurons and glial cells for extended periods, and respond to experimental manipulations. We show that iron promotes A{beta} fibrillization into long fibrils, with this process further influenced by temperature. A{beta} selectively accumulated in neurons, leading to their death, sparing glial cells. In contrast, Iron, though generally toxic to neurons, exhibited unspecific cytotoxicity. Notably, the combined presence of A{beta} and iron synergistically increased neuronal death while reducing glial cell loss. Correlation analysis revealed that this synergic interaction enhances the toxicity of each other in a mutual fashion - A{beta} directs the neuronal toxicity while iron promotes A{beta} fibrillization, leading to targeted neuronal loss. In conclusion, our findings emphasize the critical role of excess iron and A{beta} in driving neuronal death in AD, underlining the importance of targeting iron accumulation along with A{beta} clearance but also addressing in future AD therapies, while also supporting our OBSC model as a valuable platform for studying the same.

neuroscience↗

bioRxiv2022

Changes in cellular ferritin distribution of human brain tissue during autolysis revealed using analytical electron microscopy

Iron is known to accumulate in neurological disorders, so a careful balance of the iron concentration is essential for healthy brain functioning. An imbalance in iron homeostasis could arise due to the dysfunction of the proteins involved in iron homeostasis. Here, we focus on ferritin - the primary iron storage protein of the brain. Though it is known that glial cells and neurons differ in their concentration of ferritin, the change in the number of iron-filled ferritin cores or their distribution between different cell types during autolysis has not been revealed yet. Here, we show the cellular and region-wide distribution of ferritin in the human brain using state-of-the-art analytical electron microscopy. We validated the concentration of iron-filled ferritin cores to the absolute iron concentration measured by quantitative MRI and inductively coupled plasma mass spectrometry. We show that ferritins lost iron from their cores with progressing autolysis whereas the overall iron concentrations were unaffected. Though the highest concentration of ferritins was found in glial cells, we found that as the total ferritin concentration increased in a patient, ferritin accumulated more in neurons than in glial cells. Collectively our findings point out the unique behaviour of neurons in storing iron during autolysis and explain the differences between the absolute iron concentrations and iron-filled ferritin in a cell-type-dependent fashion in the human brain. Significance statementBalance of the iron load of the brain is crucial to preventing neurodegenerative disorders. Our study establishes a relation between autolysis, iron, and ferritin in the human brain with emphasis on the role of different cells in ferritin storage. We demonstrate that the iron load of ferritins does not correlate with mean iron concentrations during autolysis. Neurons retain more iron-loaded ferritin than glial cells with increasing ferritin count, which may make neurons more susceptible and exacerbate neuronal loss during iron overload. Neurons are also depleted of iron-loaded ferritin cores faster than glial cells during autolysis, demonstrating their unique role in iron storage. This paves the way to understanding the respective roles of neurons and glial cells in preventing or promoting neurodegeneration.

neuroscience↗