Biology subjects

Lee, C.-C.

Publications and source records attributed to Lee, C.-C..

23 records · Page 2Linked to original sources

bioRxiv2020

External light dark cycle shapes gut microbiota through intrinsically photosensitive retinal ganglion cells

Gut microbiota has been shown to involve in many physiological functions such as metabolism, brain development, and neuron degeneration disease. Intriguingly, many microbes in the digestive tract do not maintain a constant level of their relative abundance but show daily oscillations under normal conditions. Recent evidence indicates that chronic jetlag, constant darkness, or deletion of the circadian core gene can alter the composition of gut microbiota and dampen the daily oscillation of gut microbes. These studies suggest that the interaction between the host circadian clock and the light-dark cycle plays an important role in gut homeostasis and microbiota. However, how or whether environmental factors such as the light-dark cycle could modulate gut microbiota is still poorly understood. Using genetic mouse models and 16s rRNA metagenomic analysis, we found that light-dark cycle information transmitted by the ipRGC-sympathetic circuit was essential for daily oscillations of gut microbes under temporal restricted high fat diet condition. Furthermore, aberrant light exposure such as dim light at night (dLAN), acting through intrinsically photosensitive retinal ganglion cells (ipRGCs), could alter the composition, relative abundance, and daily oscillations of gut microbiota. Together, our results indicate that external stimulation, such as light-dark cycle information, through the sensory system can modulate gut microbiota in the direction from the brain to the gut.

neuroscience↗

bioRxiv2020

Distributed source modeling of intracranial stereoelectroencephalographic measurements

Intracranial stereoelectroencephalography (sEEG) provides unsurpassed sensitivity and specificity for human neurophysiology. However, sEEG group analyses are complicated because the electrode implantations differ greatly across individuals. Here, using an auditory experiment as the test case, we developed a distributed, anatomically realistic sEEG source-modeling approach for within- and between-subject analyses. In addition to intracranial event-related potentials (iERP), we also estimated the sources of high broadband gamma activity (HBBG), a putative correlate of local neural firing. The source models accounted for a significant portion of the variance of the sEEG measurements in leave-one-out cross-validation. After logarithmic transformations, the sensitivity and signal-to-noise ratio were linearly inversely related to the minimal distance between the brain location and electrode contacts (slope{approx}-3.6). The HGGB source estimates were remarkably consistent with analyses of intracranial-contact data. In conclusion, distributed sEEG source modeling provides a powerful neuroimaging tool, which facilitates anatomically-normalized group analyses of both iERP and HBBG.

neuroscience↗

bioRxiv2020

Adult-born neurons promote cognitive flexibility by improving memory precision and indexing

The dentate gyrus (DG) of the hippocampus is fundamental for cognitive flexibility and has the extraordinary ability to generate new neurons throughout life. Recent evidence suggested that adult-born neurons differentially modulate input to the DG during the processing of spatial information and novelty. However, how this differential regulation by neurogenesis is translated into different aspects contributing cognitive flexibility is unclear. Here, we increased adult-born neurons by a genetic expansion of neural stem cells and studied their influence during navigational learning. We found that increased neurogenesis improved memory precision, indexing and retention and that each of these gains was associated with a differential activation of specific DG compartments and better separation of memory representations in the DG-CA3 network. Our results highlight the role of adult-born neurons in promoting memory precision in the infrapyramidal and indexing in the suprapyramidal blade of the DG and together contributing to cognitive flexibility. One sentence summaryNeurogenesis improves memory precision and indexing.

neuroscience↗

bioRxiv2019

Structure based analysis of protein cluster size for super-resolution microscopy in the nervous system

To overcome the diffraction limit and resolve target structures in greater detail, far-field super-resolution techniques such as stochastic optical reconstruction microscopy (STORM) have been developed, and different STORM algorithms have been developed to deal with the various problems that arise. In particular, the effect of local structure is an important issue. For objects with closely correlated distributions, simple Gaussian-based localization algorithms often used in STORM imaging misinterpret overlapping point spread functions (PSFs) as one and this limits the ability of super-resolution imaging to resolve nanoscale local structures and leading to inaccurate length measurements. In the present study, we proposed a novel, structure-based, super-resolution image analysis method: structure-based analysis (SBA), which combines a structural function and a super-resolution localization algorithm. Using SBA, we estimated the size of fluorescent beads, inclusion proteins, and subtle synaptic structures in both wide-field and STORM images. The results showed that SBA has comparable and often superior performance to commonly used full-width-at-half-maximum parameters. We also demonstrated that SBA provides size estimations that corroborate previously published electron microscopy data.

neuroscience↗

bioRxiv2019

Cigarette Smoke Exposure Impairs β-Cell Function Through Activation of Oxidative Stress and Ceramide Accumulation

ObjectivesEpidemiological studies indicate that first- and second-hand cigarette smoke (CS) exposure are important risk factors for the development of type 2 diabetes (T2D). Additionally, elevated diabetes risk has been reported to occur within a short period of time after smoking cessation, and health risks associated with smoking are increased when combined with obesity. At present, the mechanisms underlying these associations remain incompletely understood. The objective of this study was to test the impact of CS exposure on pancreatic {beta}-cell function using rodent and in vitro models.\n\nMethodsBeginning at 8 weeks of age, C57BL/6J mice were concurrently fed high fat-diet (HFD) and exposed to CS for 11 weeks, followed by an additional 11 weeks of smoking cessation with continued HFD exposure. Glucose tolerance testing was performed during CS exposure and during the cessation period. Cultured {beta}-cells (INS-1) and primary islets were exposed ex vivo to CS extract (CSE), and {beta}-cell function and viability were tested. Since CS increases ceramide in lungs cells and these bioactive sphingolipids have been implicated in pancreatic {beta}-cell dysfunction in diabetes, islet and {beta}-cell sphingolipid levels were measured in islets from CS-exposed mice and in CSE-treated islets and INS-1 cells using liquid chromatography-tandem mass spectrometry.\n\nResultsCompared to HFD-fed ambient air-exposed mice, HFD-fed and CS- exposed mice had reduced weight gain and better glucose tolerance during the active smoking period. Following smoking cessation, CS-mice exhibited rapid weight gain and a significantly greater increase in glucose intolerance compared to non-smoking control mice. CS-exposed mice had higher serum proinsulin/insulin ratios, indicative of {beta}-cell dysfunction, significantly lower {beta}-cell mass (p=0.02), and reduced {beta}-cell proliferation (p=0.006), and increased islet ceramide accumulation. Ex vivo exposure of isolated islets to CSE was sufficient to increase islet ceramide accumulation, reduce insulin gene expression and glucose-stimulated insulin secretion, and increase {beta}-cell oxidative and ER stress. Treatment with the antioxidant N-acetylcysteine, markedly attenuated the effects of CSE on ceramide levels, restored {beta}-cell function and survival, and increased cyclin D2 expression, while also reducing activation of {beta}-cell ER and oxidative stress.\n\nConclusionsOur results indicate that CS exposure inhibits insulin production, processing, and secretion and reduced {beta}-cell viability and proliferation. These effects were linked to increased {beta}-cell oxidative and ER stress and ceramide accumulation. Mice fed HFD continued to experience detrimental effects of CS exposure even during smoking cessation. Elucidation of mechanisms by which CS exposure impairs {beta}-cell function in synergy with obesity will help design therapeutic and preventive interventions for both active and former smokers.

molecular biology↗