Significance: Light is a good probe for studying the nanoscale-level structural or molecular-specific structural properties of brain cells/tissue due to stress, alcohol, or any other abnormalities. Chronic alcoholism during pregnancy, i.e., fetal alcoholism, being teratogenic, results in fetal alcohol syndrome, and other neurological disorders. Understanding the nano-to-submicron scale spatial structural properties of pup brain cells/tissues using light/photonic probes could provide a plethora of information in understanding the effects of fetal alcoholism.
Aim: Using both light scattering and light localization techniques to probe alterations in nano- to-submicron scale mass density or refractive index fluctuations in brain cells/tissues of mice pups, exposed to fetal alcoholism.
Approach: We use the mesoscopic physics-based dual spectroscopic imaging techniques, partial wave spectroscopy (PWS) and molecular-specific inverse participation ratio (IPR) using confocal imaging, to quantify structural alterations in brain tissues and chromatin/histone in brain cells, respectively, in 60 days postnatal mice pup brain, exposed to fetal alcoholism.
Results: The finer focusing PWS analysis on tissues shows an increase in the degree of structural disorder strength in the pup brain tissues. Furthermore, results of the molecular-specific light localization IPR technique show an increase in the degree of spatial molecular mass density structural disorder in DNA and a decrease in the degree in histone.
Conclusions: In particular, we characterize the spatial pup brain structures from the molecular to tissue levels and address the plausible reasons for such as mass density fluctuations in fetal alcoholism.
The quantitative measurement of nanoscale structural alterations in cells/tissues is important to understand their physical states. Molecular specific light localization technique and microscopic imaging are highly sensitive spectroscopic approaches for studying the structural abnormalities in brain cells under a sedative condition. Fetal alcohol syndrome and other neurological disorders are the severe, irreversible outcomes of fetal alcoholism. The alcohol consumed by a pregnant mother passes through the placenta to the growing womb and inhibits the growth of vital organs of the baby resulting in brain damage and other birth defects. This damage is initially at the nanoscale level in cells/tissue. We probe fetal alcoholic pup brain cells using dual spectroscopy approaches: 1) photonics localization method using inverse participation ratio via confocal imaging, confocal-IPR, to probe DNA and histone molecular spatial structural alterations; 2) a recently developed spectroscopic technique, partial wave spectroscopy (PWS), which combines mesoscopic physics with microscopic imaging and detects the nano to submicron scales alterations in pup’s brain cells/tissues. The molecular structural abnormalities calculated based on light localization properties show an increase in the degree of spatial molecular structural disorder in DNA and a decrease in histone. An increase in spatial disorder in DNA may suggest DNA unwinding while reduced structural disorder in histone may indicate the release of histone from the DNA and helps in the unwinding of the DNA and gene expression. This result is further supported by the PWS result which shows an increase in the degree of structural disorder in chronic alcohol-treated mice pup’s brain tissues.
Photonics localization due to light scattering is an important probe to understand the molecular specific structural changes in brain cells due to diseases or abnormalities. Chronic alcoholism is associated with medical, behavioral, and psychological problems including physical damage in brain cells/tissues. The effects of chronic alcoholism on brain cells/tissue structures at the nanoscale are not well understood. On the other hand, probiotic treatment has shown some reversing effect in curing the abnormalities in an alcoholic’s brain. In this work, we study the effect of probiotic, Lactobacillus Plantarum treatment on chronic alcoholic brain cells/tissues using a mouse model. We evaluate the light localization properties of molecular specific spatial mass density fluctuations based on mesoscopic physics-based inverse participation ratio via confocal imaging of cells, confocal-IPR technique. Using the technique, we probe overexpression of astrocyte and microglial cells, and chromatin structures of different brain cells, by probing molecular specific overexpression by staining the cells with appropriate dye/proteins and then calculating the degree of spatial molecular structural disorder (Ld). The confocal-IPR analysis of alcoholic astrocytes, microglia, and chromatin of the mice brain cells show an increase in the structural disorder indicating that alcohol has an adverse effect on different brain cells and nuclei. Whereas the normalcy in the structural disorder of these brain cells happens when probiotics were fed simultaneously with alcohol, confirms the improvement in chronic alcoholic brain health. The potential application of this novel approach to diagnosing the alcohol effect and probiotic treatment in the alcoholic brain is explored.
We report mesoscopic physics based nanoscale sensitive partial wave spectroscopy (PWS) study of the structural changes in brain hippocampal region due to chronic stress induced by a stress hormone in a mouse model. Our results show that the change in the average degree of structural disorder in hippocampal tissues from stressed hormone induced mice brains has a higher structural disorder value relative to that of controlled mice, and the change is in correlation with the duration of the stress. Furthermore, the structural changes are peaked around the mid hippocampal regions, both sides of the hippocampal tissues centering around the ventricle.
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