Biology subjects

Sun, M. S.

Publications and source records attributed to Sun, M. S..

5 recordsLinked to original sources

bioRxiv2026

Third Trimester-Equivalent Alcohol Exposure Induces Sex-Dependent Alterations in Locomotor Activity, Anxiety-Risky Behaviors, and Enhances Mechanical Allodynia in Adulthood

Prenatal alcohol exposure (PAE) causes fetal alcohol spectrum disorders (FASDs), which are neurodevelopmental conditions characterized by behavioral dysregulation, learning deficits, and cognitive inflexibilities. Alcohol exposure is harmful at all stages of human gestation, including the third trimester. This developmental window--characterized by rapid brain growth, myelination, and neural circuit formation--may be particularly vulnerable, yet the long-lasting behavioral and sensory consequences of exposure during this period remain poorly understood. In this study, neonatal mouse pups were exposed to ethanol (EtOH) or air vapor from postnatal day (P) 4 to P8, which is equivalent to a third-trimester alcohol exposure (TTAE) in humans. Blood ethanol concentrations measured at P8 reached approximately 250 mg/dL, consistent with binge-level exposure. Air- and EtOH-exposed mice were then assessed as adults at 5-6 months of age for locomotor activity, anxiety-related risky behaviors, recognition memory, and increased susceptibility to peripheral neuropathy, as indicated by sensitization to light touch following minor chronic constriction injury (mCCI) of the sciatic nerve. We found that TTAE was sufficient to produce long-lasting behavioral outcomes in a sex-dependent manner. Notably, EtOH-exposed males exhibited increased spontaneous locomotor activity and risky behavior, whereas EtOH-exposed females showed minimal or decreased changes compared to their respective controls. However, both EtOH-exposed male and female mice exhibited marked increases in light-touch sensitization, referred to as mechanical allodynia, following mCCI, a response absent in air-exposed controls. Together, these findings reveal that TTAE is highly detrimental to behavioral regulation and creates a vulnerability to developing neuropathic pain in adulthood.

neuroscience↗

bioRxiv2026

Exercise-induced Sweat Promotes Wound Healing in Diabetic Foot Ulcers

Persistent hyperglycemia impairs wound healing in diabetic patients, and severe cases may even lead to disability or death. Glycemic control alone cannot effectively prevent the occurrence of diabetic foot ulcers, a serious complication of diabetes. However, safe, efficient, and cost-effective therapies remain unavailable and are urgently needed. Using a novel sports medicine paradigm, we predicted, based on reverse-transcriptomics, that exercise-induced sweat has the potential to promote would healing in diabetic foot ulcers. Subsequent animal experiments demonstrated that sweat can indeed promote re-epithelialization and collagen deposition, upregulate the expression of the proliferation marker Ki-67, the angiogenesis marker CD31, and -SMA, and significantly accelerate wound healing in a mouse model of diabetic foot ulcers. This study provides a new direction for sports medicine and offers a novel therapeutic strategy for patients with diabetic foot ulcers.

zoology↗

bioRxiv2025

Prenatal alcohol exposure promotes nerve injury-induced pathological pain following morphine treatment via NLRP3-mediated peripheral and central proinflammatory immune actions.

Adverse in-utero conditions may exert a lifelong impact on neuroimmune function. Our prior work showed that prenatal alcohol exposure (PAE) increases pathological pain sensitivity (allodynia) following peripheral sciatic nerve injury. While the immune mechanism(s) of PAE-induced immune dysfunction are poorly understood, prior studies implicated the involvement of Toll-like receptor 4 (TLR4) and the nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasomes. Interestingly, emerging data suggest a surprising overlap of spinal glial proinflammatory activation via the TLR4-NLRP3-interleukin (IL)-1{beta} axis due to opioid treatment in nerve-injured non-PAE rodents. Considering this preclinical evidence, we explored whether PAE poses a risk factor in creating proinflammatory immune bias consequent to opioid (morphine) exposure. We hypothesized that under nerve injury conditions, PAE may interact with morphine, promoting peripheral and CNS proinflammatory factors in a NLRP3-dependent manner. Using a minor nerve injury model in adult mice, we demonstrate that PAE prolongs the chronicity of ongoing allodynia in both sexes, with a more pronounced effect observed in male mice. Our study shows that PAE amplifies proinflammatory responses at the injury site and the spinal cord, driving morphine-prolonged allodynia through NLRP3 inflammasome activation. Furthermore, high mobility group box 1 (HMGB1), a well-established pain-promoting TLR4 agonist, is elevated in allodynic PAE mice. NLRP3 inhibitor, MCC950, effectively reverses morphine-induced allodynia and reduces Caspase-1 activity, IL-1{beta}, and related proinflammatory factors. Although few sex-specific effects were observed, our data convincingly support that PAE and morphine interactions ultimately converge on NLRP3-driven mechanisms in both sexes. Together, this study suggests that PAE modulates later-life neuroimmune function and provides critical insights into immune regulators underlying PAE-induced biological vulnerability to pathological pain processing and adverse effects of opioids.

neuroscience↗

bioRxiv2024

Coordination of protein synthesis and decay in mammalian cells

The maintenance of cellular homeostasis requires tight regulation of proteome concentration and composition. To achieve this, protein production and elimination must be robustly coordinated. However, the mechanistic basis of this coordination remains unclear. Here, we address this question using quantitative live cell imaging, computational modeling, transcriptomics, and proteomics approaches. We found that protein decay rates systematically adapt to global alterations of protein synthesis rates. This adaptation is driven by a core passive mechanism supplemented by facultative changes in mTOR signaling. Passive adaptation hinges on changes in the production rate of the machinery governing protein decay and allows partial maintenance of the cellular proteome. Sustained changes in mTOR signaling provide an additional layer of adaptation unique to naive pluripotent stem cells, allowing near-perfect maintenance of proteome composition. Our work unravels the mechanisms protecting the integrity of mammalian proteomes upon variations in protein synthesis rates.

cell biology↗

bioRxiv2024

Maternal Alcohol Drinking Patterns Predict Offspring Neurobehavioral Outcomes

SIGNIFICANCEThe timing, rate, and quantity of gestational alcohol consumption, collectively referred to here as Maternal Drinking Patterns (MDPs), are of known importance to fetal developmental outcomes. Though studies in rodents exist that have investigated the impact of gestational alcohol drinking characteristics, few have sought to determine the impact of MDPs on offspring behavioral outcomes. METHODSWe first used specialized equipment to record the precise amount and timing of binge alcohol consumption in pregnant mouse dams, and then characterized MDPs using Principle Component Analysis (PCA). We focused these analyses on the first fifteen minutes of every gestational drinking session when dams consumed the majority of each sessions alcohol (a phenomenon known as front-loading), as well as the entire 2 hour session across all days of gestation. We next tested offspring in open field and rotarod assays and evaluated these behavioral results in the context of MDPs. RESULTSMale alcohol exposed mice exhibited longer latencies to fall on the rotarod compared to their controls, which we attribute to a delayed decrease in body weight-gain not observed in females. This effect was found to be associated with MDPs within the first fifteen minutes of drinking, but not other MDPs. Female alcohol exposed mice had significantly reduced total locomotor activity in the open field compared to controls, and this effect was also associated with MDPs but only of the entire drinking session. Surprisingly, total gestational alcohol consumption alone was not associated with any particular behavioral outcome. Furthermore, we replicated robust behavioral data demonstrating development of allodynia in alcohol exposed mice where it did not develop in controls. CONCLUSIONSTo our knowledge, this report represents the highest resolution assessment of alcohol drinking throughout gestation, and one of few to have identified relationships between specific alcohol MDPs and neurobehavioral outcomes in offspring. Specifically, based on characteristics of the PCA groups, we found evidence that the rate of alcohol front-loading leads to developmental delays in males, whereas an interaction of front-loading rate and duration, overall persistence, and total amount consumed lead to a female-only decrease in locomotor activity. Beyond these results, we provide a method for precise and accessible tracking of such data.

neuroscience↗