Animal Experimentation and Research Commons^™

Effects Of Novel Dopamine D4 Receptor-Targeted Compounds On Locomotor Activity And Anxiety-Like Behavior In Male And Female Sprague Dawley Rats, Samantha Alyse Walkow, Noah A. Ivak, Daniel Chandler, John Tkaczynski, Thomas M. Keck, Comfort A. Boateng, Eleni Papadopoulos, Barry D. Waterhouse, Rachel L. Navarra

Rowan-Virtua Research Day

The consequences of modulating subtypes of G protein coupled dopamine receptors are broadly studied for their role in decision making behavior, specifically in situations involving uncertain risk and reward. The actions of dopamine D4 receptors (D4Rs) on these complex processes are the least understood, particularly due to a lack of available compounds with suitable selectivity for D4Rs. Further, current research often fails to evaluate how modulating specific dopamine receptor subtypes may affect locomotor activity and anxiety-like behavior as confounding factors prior to assessing their function in behavioral assays of higher order decision making. The goal of the current study was …

Assessing Sleep Quality In A Preclinical Model Of Low Back Pain Through Novel Noninvasive Methods, Lydia C. Saltz

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Chronic low back pain (LBP) has widespread negative impacts on quality of life. Current treatments for chronic LBP fail to provide long-term efficacy and motivate the need to understand key drivers of poor patient outcomes. Mounting evidence indicates that sleep disturbances and chronic LBP have a strong reciprocal relationship. Women may be particularly vulnerable to the negative impacts of the sleep-pain axis, exhibiting greater prevalence in both conditions. However, the relationship between sleep, pain, and sex remains understudied. Preclinical models can be used to parse out characteristic sleep features that degrade with pain, which can be further broken out by …

The Role Of Ucp2 In Pancreatic Cancer Metabolism And Its Potential As A Radiosensitizer, Emily Rieff

Dissertations and Theses (Open Access)

Uncoupling protein 2 (UCP2) is a mitochondrial protein that regulates the flow of protons down the gradient established by the electron transport chain (ETC) without generating ATP, thus uncoupling the proton gradient from ATP generation. In tumors, specifically pancreatic cancer (PDAC), the ETC is highly stimulated to generate the copious ATP needed by the tumor to grow. However, extended ETC use increases reactive oxygen species (ROS), and if left unchecked, results in cell death. To evade this, PDAC employs antioxidant strategies, including upregulating UCP2 in tumor cells. In addition to its uncoupling function, UCP2 indirectly controls ROS levels by maintaining …

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

Investigating The Role Of The Hypocretin/Orexin System In A Novel Model Of Polysubstance Dependence, Tyler Zarin

Electronic Theses and Dissertations

Substance use disorders (SUD) in the United States are steadily increasing. Potent and dangerous substances such as methamphetamine (MA) and fentanyl (FEN) are often co-used as a polysubstance (POLY), either intentionally or unknowingly as FEN is a common adulterant. SUD is characterized by physiological and psychological dependence involving the negative reinforcement of anhedonia and withdrawal which drive hypermotivated drug-taking behaviors. Current theory suggests that recruitment of hypocretin/orexin (HCRT) neuropeptide in reward and stress associated brain regions contributes to drug dependence. Despite strong evidence for HCRT’s role in mono-drug dependence, a relevant model for POLY dependence has yet to be developed, …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

Passive Integrated Transponders: An Effective Marking Technique For Individual Identification Of Anaxyrus Fowleri?, Emily Leprell

Honors College Theses

With the rise of fungal disease such as Chytridiomycosis, known as chytrid, causing massive population declines for many species of frogs and toads (order Anura), specific conservation strategies are needed now more than ever. In many cases, being able to mark and identify individuals is a necessary step in developing an effective conservation plan. Individual identification allows researchers to obtain accurate population estimates, which are needed to test the progress and validity of conservation management decisions. However, due to their unique life history, including cutaneous respiration and a dichotomous lifestyle, anurans are among the most difficult wildlife species to …

Designing An Optimal Thermal Preference Arena For Southern Cricket Frog (Acris Gryllus) Juveniles, Eleanor E. Briggs, David M. Phillips Jr.

Honors Theses

Climate change has been altering ecosystems across the world at a substantial rate, disrupting the delicate ecophysiological relationships between ecosystems and the organisms that live in them. Ectotherms, such as amphibians, rely on external temperatures to behaviorally thermoregulate, making it especially imperative to study their thermal biology. Thermal preference, which assesses the environmental temperature an organism would seek out in the absence of external stimuli, provides valuable information about an amphibian’s thermal biology and can be used to predict the effects of climate change on a species or population. A commonly used method to measure thermal preference is an arena …

Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca

MUSC Theses and Dissertations

Background: Ethanol (EtOH) consumption causes hepatocellular mitochondrial depolarization (mtDepo) and mitophagy. Here, the Aims were to develop techniques to characterize sublobular hepatocellular metabolism and the distribution of mtDepo and mitophagy after acute EtOH. Methods: Wildtype and GFP-LC3 transgenic mice were treated with EtOH or vehicle and administered the covalently labeling mitochondrial membrane potential (ΔΨ) reporter, MitoTracker Red (MTR), and/or the non-covalent ΔΨ reporter, rhodamine 123 (Rh123), prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted. Enrichment in E-cadherin (ECAD) and cytochrome P4502E1 in periportal (PP) and pericentral (PC) hepatocytes, respectively, validated …

Enhancing Topical Drug Delivery Of Apremilast Through Niosomal Gel Formulation: Ex Vivo Skin Permeation And In Vivo Evaluation For Psoriasis, Megha Shyam Matlapudi, Anka Rao Areti, Yukti Jaiswal, Veeresh Bantal, Raghavender Medishetti

The Thai Journal of Pharmaceutical Sciences

Background: Psoriasis is a dynamic and chronic disease characterized by inflammatory changes and an increased rate of keratinocyte proliferation leading to the formation of erythematous scleroderma plaques with a silvery sheen. The existing therapies come with shortcomings in terms of effectiveness and leave behind a trail of side effects. Hence, there is a need of alternative therapeutic measures. Objectives: This study aimed to assess the therapeutic potential of Apremilast Niosomal Gel (APR Nio Gel) in treating psoriasis, comparing its effectiveness with conventional gel (APR Gel) and oral suspension (APR Oral) formulations. Materials and Methods: Apremilast niosomes were prepared by thin …

Effect Of Chronic Alcohol Feeding Using The Lieber-Decarli Diet On Alzheimer’S Disease Pathology In Tg2576 Mice, Devaraj V. Chandrashekar, Nataraj Jagadeesan, Tamara Abdullah, Rudy Chang, Ross A. Steinberg, Frankey Sanchez, Elias Khal, Joshua Yang, David H. Cribbs, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background: Chronic alcohol drinking is a modifiable risk factor for Alzheimer’s disease (AD), but underlying mechanisms remain poorly understood. Most studies of alcohol feeding to AD mice have utilized young mice and delivered alcohol in drinking water without controlling nutritional intake.

Objective: To study the impact of Lieber-DeCarli (LDC) liquid alcohol diet, which balances nutritional intake, on AD pathology of aged Tg2576 and wild-type (WT) mice, which is unexplored.

Methods: 13-month-old male and female Tg2576 or WT mice were fed LDC diet (5% ethanol or control) for six weeks (n = 11-13/group). Exploration (open-field test) and spatial reference memory …

Exploring The Therapeutic Potential Of Trigonella Foenum-Graecum Extract-Loaded Transferosomal Gel In Freund's Complete Adjuvant-Induced Rat Models., Vandana Singh Ms., Hema Arya Ms., Bhavana Singh Dr., Koushal Dhamija Mr., Preeti Singh Dr., Gautam Kumar Dr.

Chulalongkorn Medical Journal

Abstract:

Background: Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by inflammation and joint damage.

Objective: This study aimed to evaluate the antiarthritic activity of Trigonella foenum-graecum (TFG) Transferosomal gel in a Freund’s adjuvant-induced arthritic rat model and compare it with Diclofenac gel, a standard anti-inflammatory drug.

Methods: Arthritis was induced in rats by injecting a 0.1 mL (1mg/ml) CFA suspension into the left hind foot in the subplantar region, allowing them to develop arthritis for 21 days.

Results: Arthritis induction led to a significant increase in paw volume, indicative of inflammation. Treatment with both TFG-transferosomal gel and Diclofenac …

External Jugular Vein Catheterization Technique For Continuous Blood Sampling In Gilts, Preechaphon Taechamaeteekul, Yosua Kristian Adi, Chutikan Srisang, Pirada Virankabutra, Natchanon Dumniem, Jinda Singlor, Padet Tummaruk

The Thai Journal of Veterinary Medicine

External jugular vein blood collection is common in gilts and sows, but continuous sampling for hormonal and pharmacokinetic research requires catheterization. The standard protocol has remained largely unchanged for nearly 40 years. This study aimed to develop a modified external jugular vein catheterization technique in gilts. Ten gilts (72.0 ± 3.4 kg) underwent surgery under general anesthesia after 12-hour fasting. Sedation was induced with intramuscular Xylazine (4.4 mg/kg) and Tiletamine–Zolazepam (2.2 mg/kg), followed by intravenous Thiopental sodium (10 mg/kg). Once anesthetized, gilts were placed in dorsal recumbency, and the external jugular fossa was prepared under sterile conditions. A 10 cm …

Impact Of Acute Stress On Circadian Rhythm Regulation Of Locomotor Activity In Syrian Hamsters, Raquel A. Villarreal, Laura E. Garcia, Mario Gil

Research Symposium

Background: Disruptions of circadian rhythms, caused by factors such as environmental changes or stress, are linked to health conditions, including metabolic disorders, cardiovascular diseases, and mood disorders. Circadian rhythm disturbances are particularly relevant for understanding the etiology of conditions like insomnia, depression, and anxiety. The circadian rhythm, primarily regulated by the suprachiasmatic nuclei (SCN) in the hypothalamus, coordinates biological processes to align with daily environmental cycles. Acute stress, especially when experienced immediately upon waking, has been shown to disrupt these rhythms, impair sleep regulation, and exacerbate mood dysregulation. Given the significant clinical implications, understanding how stress impacts circadian rhythms is …

The Role Of The Female Reproductive Cycle In Social Communication And Relevance To Mental Health, Julissa Amaro Castillo, Fernando Dominguez, Ariana Hinojosa, Giselle Padilla, Mario Gil

Research Symposium

The female reproductive cycle is characterized by fluctuating hormones, including estrogens and progesterone, that are involved in reproductive health; however, they have also been linked to disorders like Premenstrual syndrome (PMS), Premenstrual Dysphoric Disorder (PMDD), mood swings, depression and others. The goal of this study is to use the Syrian hamster (Mesocricetus auratus) as an animal model to examine the influence of the reproductive cycle and hormones on behavior. Scent-marking activity known as flank marking is exhibited by territorial or sociable animals. In essence, animals mark their territory or convey information such as reproductive status by rubbing their flanks or …

Effects Of Arginine-Vasopressin In The Brain On Cardiovascular Function In A Psychosocial Stress Animal Model, Esmeralda Lopez-Garcia, Ariana V. Hinojosa, Esperanza I. Alaniz, Fernando Dominguez, Giselle Padilla, Mario Gil

Research Symposium

Background: Psychosocial stress impacts cardiovascular health, increasing the risk of events like myocardial infarction (MI), stress cardiomyopathy, and neuropsychiatric disorders, including Major Depressive Disorder (MDD) and Anxiety. However, our understanding of the biological mechanisms that connect psychosocial stress with negative cardiovascular and psychological outcomes remains incomplete. Arginine-vasopressin (AVP) is linked to both mental and physical health by regulating social behavior, blood pressure, and anxiety-related behaviors. This study investigates the potential cardioprotective effects of the neuropeptide AVP, in an effort to generate evidence that it may strengthen heart function and lessen the severity of adverse cardiovascular events caused by stress, brain …

Investigating The Relationship Among Environmental Factors, Reproductive Status, And Stress In A Preclinical Model Of Endocrine Function In Women’S Translational Health, Bianca A. Camacho, Laura Emma Garcia, Raquel Villarreal, Mario Gil

Research Symposium

Background: The average menstrual cycle of a healthy adult woman is a duration of approximately 28 days, during which in the follicular phase (first 14 days) the progesterone hormone is at a stable level while estrogen increases to its peak level on day 14. Day 14 is known as ovulation, during which progesterone increases during its Luteinizing Hormone (LH) surge while estrogen decreases. Menses, known colloquially as a woman’s “period,” begins approximately at day 14 after ovulation and lasts an average of 7 days. The luteal phase, otherwise known as the secretory phase, lasts for the remaining 14 days until …

Exploring The Effects Of Serotonin And Ssris On The Neurological, Behavioral, And Cardiovascular Systems Under Induced Stress –Using The Animal Model Of The Syrian Hamster, Ariana V. Hinojosa, Esperanza I. Alaniz, Esmeralda Lopez-Garcia, Giselle Padilla, Fernando Dominquez, Mario Gil

Research Symposium

Background: Serotonin is a neurotransmitter that has been found to have a wide range of effects on not just the neuropsychological processes but has also been found to exert effects outside the central nervous system (CNS); regulating numerous biological processes, such as metabolism, gastrointestinal system, reproductive function, and even the cardiovascular system. However, there is still a limited understanding of how serotonin affects all these systems due to its complexity and ability to regulate homeostasis. This project aims to create a stronger foundation of knowledge about serotonin and its influence on the interaction between the CNS, behavior, and cardiac function …

Antibiotic Resistome, Mobile Genetic Elements, And Virulence Profile Of Multidrug-Resistant Enterobacteriaceae Isolated From Healthy Philippine Native Chicken As Revealed By Analysis Of Whole Genome Sequence, Alvin P. Jimenez, Grignard James R. Buday, Rina B. Opulencia

The Philippine Agricultural Scientist

Gram-negative bacteria, particularly Enterobacteriaceae, acquire antibiotic resistance via horizontal transmission of resistance genes in poultry farms that give rise to multidrug-resistant (MDR) strains. The presence of MDR strains that are potentially pathogenic and zoonotic poses a concern to animal and human health. The aims of this study were to isolate MDR, potentially pathogenic Enterobacteriaceae from Philippine native chicken (PNC) and to analyze the genome of a representative MDR isolate to gain insights into the mechanisms, acquisition, and transmissibility of antibiotic resistance genes (ARGs). Cloacal swabs from PNC were used to isolate putative Salmonella that were then tested for antimicrobial …

Contraceptive Hormone Influences On The Role Of Primary Reinforcement And Reinforcer-Enhancement In Nicotine Self-Administration, Kathleen Robin Mcnealy

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Hormonal contraceptives contain a synthetic estrogen (e.g., ethinyl estradiol/EE) and/or a synthetic progestin (e.g., levonorgestrel/LEVO) and can exacerbate nicotine intake. However, whether altered intake reflects changes in nicotine reinforcement or enhancement by nicotine of co-occurring reinforcers is unknown. This reinforcer-enhancement effect is evidenced in rats when nicotine self-administration is increased by the presence of a visual stimulus (VS) reinforcer. This dissertation examined the effects of EE and LEVO on nicotine reinforcement and reinforcer-enhancement in ovary-intact female Sprague-Dawley rats. Rats were implanted with a jugular catheter and assigned to receive daily injections of EE (Vehicle, 0.125 [Low], or 0.18 [High] μg/day; …

The Impact Of Diabetes On Neurovascular Integrity: A Special Focus On Pericytes And Endothelin-1, Mia Edgerton

MUSC Theses and Dissertations

Diabetes increases the risk of stroke and Vascular Contributions to Cognitive Impairment and Dementia (VCID). Diabetes also dysregulates the endothelin (ET) system. ET-1-mediated constriction of brain microvascular pericytes (BMVPCs) has been shown to contribute to brain hypoperfusion. However, there is a loss of BMVPCs in VCID, but underlying mechanisms of pericyte degeneration are poorly studied. ETA receptor activation can instigate phenotypical changes and cellular senescence in endothelial cells. . There is also emerging evidence that ETB receptor agonism improves outcomes in patients with cerebral ischemic stroke, but long-term effects, especially in diabetes, are unknown. Therefore, this study aimed to determine …

Impact Of Resistance Training On Bone During 40% Caloric Restriction In Growing Female Rats, Ken D. Sumida, Daniel L. Smithers, Aaron Gerston, Kim A. Lagerborg, S. Victoria Jaque, Fred Caporaso

Food Science Faculty Articles and Research

There is a growing trend in the use of severe caloric restrictive diets among normal weight young females that can jeopardize bone health. Using an animal model, the purpose of this study was to determine whether resistance training (RT) could maintain bone health during a 6-week severe caloric restrictive (CR) diet in growing female rats. Twenty-four female rats (~ 8 weeks old) were randomly divided into the following groups: sedentary rats fed a normal diet (N = 8), sedentary rats fed a 40% CR diet (D = 8), and an RT group fed a 40% CR diet (DT …

Local Tissue Damage Treatment Of Snake Venom, Suchitra Khunsap

The Thai Journal of Veterinary Medicine

Local tissue damage caused by snake envenomation was a medical problem that caused morbidity and mortality for more than a decade, with no defined treatment guidelines. Nowadays, antivenom is the primary treatment for snakebite, which substantially reduces systemic venom but not significantly reducing local symptoms. We compiled a list of local damage therapies, including antivenom medication, surgery and skin grafting, small molecule medicines, and alternative therapies. Although each was not approved as a standard treatment, it may be a treatment option for tissue damage caused by snake venom. However, antivenoms and most resistant compounds may not be the best strategy …

Studying The Impact Of Weather Changes On Bird Breeding., Perle Suana, Yangyang Tao

Posters-at-the-Capitol

Climate change start to impact our daily life recently. The shifting climate introduces frequent and unpredictable temperature fluctuations. For species like birds, particularly those that reproduce through eggs, maintaining stable temperatures during incubation is crucial for reproductive success. Despite the significance of temperature stability, limited research has delved into understanding the thresholds of temperature tolerance during incubation. In this investigation, we will apply the data science tools to analyze the local temperature dataset over the past decade and the birds incubation dataset. Our aim was to explore potential correlations between extreme temperature swings coinciding with the breeding season and instances …

Brain Delivery Of Erythropoietin Results In A Significant Reduction Of Brain Aβ And Spatial Memory Deficits In The App Knock-In Mouse Model, Rudy Tieu Chang, Devaraj V. Chandrashekar, Grace-Ann Chuli Roules, Emi Iwasaki, Nataraj Jagadeesan, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Although novel treatments for Alzheimer’s disease (AD) have begun to show modest therapeutic effects, agents that target hallmark AD pathology and offer neuroprotection are desired. Erythropoietin (EPO) is a glycoprotein hormone with neuroprotective effects but is faced with challenges including limited brain uptake and increased hematopoietic side effects with long-term dosing. Therefore, EPO has been modified and bound to a chimeric transferrin receptor monoclonal antibody (cTfRMAb); the latter shuttles EPO past the blood-brain barrier (BBB) into brain parenchyma and reduces its plasma exposure and potential for side effects. Our study sought to characterize the safety and pharmacokinetics (PK) of …

Chronic Heavy Alcohol Intake And Liver-Specific Lrp-1 Reduction Increase Amyloidosis In Alzheimer’S Disease Mice, Devaraj V. Chandrashekar, G. Chuli Roules, Ross A. Steinberg, Urvashi R. Panchal, Nataraj Jagadeesan, Adenike Oyegbesan, Trinh Roselyn, Joshua Yang, Sharda R. Bhagwat, Hiya Rakholia, Rutvi D. Mevawala, Moom Roosan, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Chronic heavy alcohol drinking may be a modifiable risk factor for Alzheimer’s disease (AD), but studies in rodent AD models more closely mimic chronic moderate alcohol drinking in humans and largely focus on the brain. The role of the liver, which is significantly impacted by chronic heavy alcohol intake, in driving brain changes in alcohol-dependent AD remains unexplored. Our study using intragastric-ethanol feeding, which mimics chronic heavy alcohol intake in humans, in C57BL/6J mice showed significant AD-relevant changes in the brain and liver. Therefore, we aimed to investigate how hepatic changes using this model of chronic heavy drinking drive …

Effectiveness Of Maternal Bovine Appeasing Substance Administered To Newly Received, High-Risk Stocker Calves, Elle Johnston, Rosie Whittle, Robin Cheek, Beth Kegley, Jeremy Powell, Shawna Weimer

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

Stocker cattle purchased at auction can be susceptible to disease due to the stressors associated with the auction process and are referred to as “high-risk.” The objective of this study was to determine the efficacy of a maternal bovine appeasing substance, FerAppease^®, on the growth performance, health, and behavior of stocker cattle. Male beef calves (n = 80) were purchased at auction and transported to the University of Arkansas System Division of Agriculture Savoy Research Complex Beef Stocker Unit. On day 0, bulls were castrated, and steers and bulls were assigned to 8 pens (n = 10 calves/pen; …

Equine Hair Cortisol Concentration And The Effects Of Season, Storage Method, And Personality Traits, Savannah M. Rivers, Grace A. Robertson, Thomas Powell, Lydia O'Sullivan, Shea Porr

Murray State Theses and Dissertations

Stress exists everywhere, for survival, adaptation is necessary. These adaptations directly reflected the stresses the animal experienced and demonstrated the ability to cope. An animal that could not cope could not survive. Stressful experiences resulted in behavior patterns for each animal. Consistent behavior can be defined as personality [1]; therefore, stress could directly influence personality by changing behavior.

Stress research helped analyze and identify animal personality traits, especially horses. Human-horse pairings partially relied on personality traits and, when considered, often led to improvements in welfare [2]. There are various tools to assess personality, one being Equine Personality Assessment [3]. The …

Husbandry Of Jellyfish And Ctenophores: Why Gelatinous Forms Thrive In Their Natural Habitat And Yet Often Struggle To Survive In Aquaria, Regina Garza Ramirez

Undergraduate Theses and Capstone Projects

Recent observations in the behaviors of several gelatinous forms in the wild have demonstrated that human impacts to their environment have likely accelerated growth of their populations tremendously. Interestingly enough, population growth of jellyfish and ctenophores in aquariums and artificial habitats is less often observed under controlled conditions, while they often bloom in rapidly changing environments of nature. Seeking the knowledge of aquarists and researchers that have worked directly with gelatinous animals through interviews, and documenting the experiences of each individual, allowed acquisition of data that can be used to compare the reproductive success of these animals in captivity and …

Identifying Notch-Regulated Genes Using A Specific Notch Signaling Inhibitor, Hammed Gafar

EWU Masters Thesis Collection

Bone remodeling is a dynamic process that requires a balance between bone resorption by osteoclasts and bone formation by osteoblasts to maintain skeletal integrity. Disruptions to this equilibrium can lead to pathological conditions such as osteoporosis. Osteoclasts originate from macrophages, and their differentiation is regulated by several signaling pathways, notably the notch signaling pathway. Gamma-secretase, an enzyme crucial for initiating notch signaling, can be inhibited by DAPT. However, DAPT also targets non-Notch substrates, complicating the identification of genes specifically regulated by Notch. To address this limitation, this study employed IMR-1A, a selective Notch pathway inhibitor that disrupts the assembly of …