Animal Experimentation and Research Commons^™

Internal Vertebral Morphology Of Bony Fishes Matches The Mechanical Demands Of Different Environments, Dana Baxter, Karly E. Cohen, Cassandra M. Donatelli, Eric D. Tytell

Engineering Faculty Articles and Research

Fishes have repeatedly evolved characteristic body shapes depending on how close they live to the substrate. Pelagic fishes live in open water and typically have narrow, streamlined body shapes; benthic and demersal fishes live close to the substrate; and demersal fishes often have deeper bodies. These shape differences are often associated with behavioral differences: pelagic fishes swim nearly constantly, demersal fishes tend to maneuver near the substrate, and benthic fishes often lie in wait on the substrate. We hypothesized that these morphological and behavioral differences would be reflected in the mechanical properties of the body, and specifically in vertebral column …

Effects Of Chronic Cirrhosis Induced By Intraperitoneal Thioacetamide Injection On The Protein Content And Michaelis–Menten Kinetics Of Cytochrome P450 Enzymes In The Rat Liver Microsomes, Devaraj Venkatapura Chandrashekar, Barent N. Dubois, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Chronic intraperitoneal injection of thioacetamide (TAA) in rats has been used as an animal model of human cirrhosis to study the effects of the disease on drug metabolism. However, TAA inhibits P450 enzymes directly and independently of cirrhosis. We investigated the effects of chronic cirrhosis in rats, induced by 10 weeks of intraperitoneal TAA, on the P450 enzymes after a 10-day washout period to eliminate TAA. Liver histology and serum biomarkers of hepatic function confirmed cirrhosis in all animals. Microsomal total P450 content, P450 reductase activity and ethoxycoumarin O-deethylase activity, a general marker of P450 activity, were significantly reduced by …

Differential Expression And Activities Of Cytochrome P450 3a In The Rat Brain Microsomes And Mitochondria, Nouf Alshammari, Devaraj Venkatapura Chandrashekar, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ), a benzodiazepine derivative, is metabolized to 1′- and 4-hydroxylated metabolites (1′-OH-MDZ and 4-OH-MDZ, respectively) by cytochrome P450 3A (CYP3A). The purpose of this study was to investigate the CYP3A-mediated hydroxylation of MDZ in the rat brain mitochondria (MT). Brain microsomes (MC) and MT fractions were prepared from rats (n = 8) using differential and density gradient centrifugations, and the purity of the fractions was evaluated using VDAC1 and calreticulin as markers of MT and MC, respectively. The formation rates of 1′-OH-MDZ and 4-OH-MDZ in the rat brain MC and MT samples were determined using an LC–MS/MS method …

Early Life Exposure To Unpredictable Parental Sensory Signals Shapes Cognitive Development Across Three Species, Elyssia Poggi Davis, Kari Mccormack, Hina Arora, Desiree Sharpe, Annabel K. Short, Jocelyne Bachevalier, Laura M. Glynn, Curt A. Sandman, Hal S. Stern, Mar Sanchez, Tallie Z. Baram

Psychology Faculty Articles and Research

Exposure to early life adversity has long term consequences on cognitive function. Most research has focused on understanding components of early life adversities that contribute to later risk, including poverty, trauma, maltreatment, and neglect. Whereas these factors, in the aggregate, explain a significant proportion of emotional and cognitive problems, there are serious gaps in our ability to identify potential mechanisms by which early life adversities might promote vulnerability or resilience. Here we discuss early life exposure to unpredictable signals from the caretaker as an understudied type of adversity that is amenable to prevention and intervention. We employ a translational approach …

Efficacy And Safety Of A Brain-Penetrant Biologic Tnf-Α Inhibitor In Aged App/Ps1 Mice, Weijun Ou, Yuu Ohno, Joshua Yang, Devaraj V. Chandrashekar, Tamara Abdullah, Jiahong Sun, Riley Murphy, Chuli Roules, Nataraj Jagadeesan, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Tumor necrosis factor alpha (TNF-α) plays a vital role in Alzheimer’s disease (AD) pathology, and TNF-α inhibitors (TNFIs) modulate AD pathology. We fused the TNF-α receptor (TNFR), a biologic TNFI that sequesters TNF-α, to a transferrin receptor antibody (TfRMAb) to deliver the TNFI into the brain across the blood–brain barrier (BBB). TfRMAb-TNFR was protective in 6-month-old transgenic APP/PS1 mice in our previous work. However, the effects and safety following delayed chronic TfRMAb-TNFR treatment are unknown. Herein, we initiated the treatment when the male APP/PS1 mice were 10.7 months old (delayed treatment). Mice were injected intraperitoneally with saline, TfRMAb-TNFR, etanercept (non-BBB-penetrating …

The Effect Of Infection Risk On Female Blood Transcriptomics, Brenna M. G. Gormally, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Defenses against pathogens can take on many forms. For instance, behavioral avoidance of diseased conspecifics is widely documented. Interactions with these infectious conspecifics can also, however, lead to physiological changes in uninfected animals, an effect that is much less well understood. These changes in behavior and physiology are particularly important to study in a reproductive context, where they can impact reproductive decisions and offspring quality. Here, we studied how an acute (3 h) exposure to an immune-challenged male affected female blood transcriptomics and behavior. We predicted that females paired with immune-challenged males would reduce eating and drinking behaviors (as avoidance …

Modulation Of Hepatic Amyloid Precursor Protein And Lipoprotein Receptor-Related Protein 1 By Chronic Alcohol Intake: Potential Link Between Liver Steatosis And Amyloid-Β, Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter Van Der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Syndey M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting …

Prenatal Choline Supplementation During Maternal Obesity Alters Offspring Response To Western Diets, Hunter W. Korsmo

Dissertations, Theses, and Capstone Projects

Maternal obesity has led to an increase in adverse offspring developmental outcomes and a greater risk for long-term metabolic diseases. Choline, a semi-essential nutrient, can be incorporated into phosphatidylcholine (PC) as well as sphingomyelin (SM) and donate its labile methyl group for the remethylation of homocysteine after choline is oxidized to betaine. Prenatal choline insufficiency has been related to maternal obesity and metabolic diseases, such as metabolic associated fatty liver disease (MAFLD). Choline may interact with maternal obesity to influence the programming offspring.

Chapter 1 presents an introduction of choline and the various clinical outcomes associated with choline supplementation during …

Impacts On Fast-Start Performance: How Do Group Size And Habitat Degradation Alter The Escape Behavior Of A Schooling Coral Reef Fish?, Monica D. Bacchus

All HCAS Student Capstones, Theses, and Dissertations

Escaping predation is essential for species survival, but prey must effectively match their response to the perceived threat imposed by a predator. Fish evaluate their surroundings using several sensory stimuli, including olfactory, visual, auditory, and mechanical cues. A range of taxa use the fast-start response to evade predators, including fishes, sharks, and larval amphibians. While the fast-start response (rapid bursts of swimming) is extensively studied in solitary fishes, the factors that mediate the collective escape response in schools of fish have historically been investigated far less. To address this knowledge gap, the collective escape behavior and individual escape performance of …

Effect Of Sensory Additives On Sow Lactation Performance, Subsequent Reproductive Performance, And Nursey Pig Performance, Nathan E. Davis

Graduate Theses and Dissertations

Maximizing nutrient intake during lactation is vital to sow performance as well as litter performance. The aim of these studies was to evaluate the impact of a sensory additive on sow lactation performance and nursery pig performance. Five groups of sows were farrowed, three during winter (October, December and January) and two during summer months (June, July, August). Sows were weighed, and back fat depth was measured, at 110 d of gestation prior to entering the lactation room, and again at weaning. The sows were blocked by parity, and then allotted by BW at d 110 to Control or 0.075% …

Early-Exercise Effects On Mice Tendon Remodeling, Miles Valencia

Electronic Theses, Projects, and Dissertations

Tendons connect and transmit energy between muscles and bones and play a key role in movement. Tendon remodels by breaking down and absorbing tendon components including collagen fibers and elastin while replacing them with newly formed tendon. These processes can be influenced by short- and long-term factors such as exercise and aging; the magnitude of influence on tendon remodeling remains unclear. I researched the effects of maturation and exercise on tendon remodeling using a mice colony artificially selected for high voluntary wheel running called high-runner mice. Control and high-runner linetype mice were separated into 2 age cohorts that started training …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

The Role Of Microbiota On Campylobacter Jejuni Colonization And Growth Performance In Broiler Chickens, Ayidh Almansour

Graduate Theses and Dissertations

The successful poultry production at modern era comes from the vertical integratedindustrialization, which has fundamentally changed how animals have been living for millions of years. Antimicrobial growth promoters have been used to sustain the efficient industrialized animal production, driving antimicrobial overuse and resistance. Because of the increasing pressure from consumer’s concerns and government regulations, it is urgent to develop antimicrobial free alternatives as growth promoters in poultry production, but few effective antimicrobial alternatives are currently available. Campylobacter jejuni is one of the worldwide prevalent foodborne bacterial pathogens mainly transmitted from poultry. However, few mechanisms are available on why C. jejuni …

Intestinal Microbiota Analysis Of Broiler Chickens Under Necrotic Enteritis Challenge And Tributyrin Supplementation, Taylor Nicole Mckinney

Graduate Theses and Dissertations

Poultry is a staple protein source for most of the planet. Until recently, antibiotic growth promoters (AGPs) were used to prevent illnesses in commercial chicken production. Currently, this is not possible due to regulations and consumer concern, but without such a preventative, diseases like necrotic enteritis (NE) have reemerged, posing a threat to bird health, and ultimately, our food source. Necrotic enteritis is a severe gastrointestinal disease caused by the gram-positive pathogen, Clostridium perfringens. Clinical features of this disease are diarrhea, intestinal lesions, and death, with a high transmission rate. In a subclinical form, growth performance is diminished and is …

Effects Of An Injectable Zinc Solution At Weaning As An Alternative Castration Method In Beef Cattle, Reagan Nicole Cauble

Graduate Theses and Dissertations

Two experiments were conducted to investigate a 1 mL intratesticular zinc (100 mg Zn) injection administered into each testicle at weaning (Z) and its effects on growth, health, behavior and testosterone. In the first experiment, beef bulls were assigned randomly to treatment at birth: 1) surgically castrated at birth (S; n = 37) or 2) Z (n = 37). Testicular thickness differed by day (P < 0.01) for Z. Testosterone concentrations were greater in Z by d 77 and remained so through d 280 (P = 0.02) compared to S. Zinc injected calves were heavier at the trail’s conclusion (P ≤ 0.04), had greater ADG overall (P < 0.01), heavier hot carcass weight (P = 0.01), and greater lean muscle area (P = 0.01) compared to S; but a lower marbling score (P < 0.01). Yield Grade, dressed carcass yield and fat thickness were similar (P ≥ 0.14). Zinc injected calves had greater haptoglobin (Hp) concentrations (P < 0.01). Zinc injected calves had greater concentrations of white blood cells on d 1 and 2 and greater concentrations and proportions of neutrophils on d 1, 2 and 3 (P < 0.01). Conversely, S had a greater percentage of lymphocytes on d 1, 2 and 3 and a lower ratio of neutrophils to lymphocytes during that same time (P < 0.01). Zinc injected calves spent more time on their side or sternum on d 1 and more time on their side on d 2 while S spend more time standing during that time (P < 0.01). During d 3, 4, 5, and 6, Z stood more while S laid on their sternum (P < 0.01). In trail 2, beef bulls were allocated randomly to treatment one week post weaning: 1) banded (B; n = 42) or 2) Z (n = 39). Body weights were similar (P ≥ 0.39) but ADG improved for Z compared to B (P = 0.05). Testosterone concentrations were greater in Z compared to B (P ≤ 0.02). Testicular width in Z differed by d (P < 0.01). Zinc castrated calves spent more time on their side compared to B one day post castration (P = 0.03) until d 3 and 4 where B spent more time on their side (P ≤ 0.02). Banded calves stood more the first two days (P ≤ 0.01). On days 3, 4, 5, and 6, Z stood more (P ≤ 0.01) while B were on their sternum (P ≤ 0.03). Banded calves had lower Hp concentrations compared to Z (P ≤ 0.01). Total white blood cell concentrations, proportions and concentrations of neutrophils, and proportion of lymphocytes were greater in Z compared to B on d 1, 2, and 3 (P ≤ 0.01). There was no interaction between treatments over time for IL1β, IL6, and TNFα expression (P ≥ 0.83). The findings in both studies indicate that intratesticular Zn injections at weaning can improve growth performance and some carcass attributes but produce a heightened inflammatory and immune response and cause discomfort. Injecting zinc, as formulated and administered in these trails, does not result in complete castration of beef calves at this age and therefore cannot be considered a true castration alternative.

The Role Of Temperature Variation On Macrophage Physiology And Function In Vitro In Mice, Chicken, And Fish, Intisar Abdullah Hassan

Graduate Theses and Dissertations

Fever is an essential component of the immune response. Baseline body temperatures vary in different species, and fever represents increased temperature over baseline. Fever initiates and enhances immune responses as well as creates an environment in which the body has advantages over pathogens. Macrophages are often the first line of cells that come in contact with pathogens, asthey reside in and traffic through tissues. They are important for their engulfment of pathogens that results in the digestion of the pathogen, and they also produce nitric oxide and cytokines that contribute to immune responses in a variety of ways, including initiating …

Ciliogenesis Mechanisms Mediated By Pak2-Arl13b Signaling In Brain Endothelial Cells Is Responsible For Vascular Stability, Karthikeyan Thirugnanam, Shubhangi Prabhudesai, Emma Van Why, Amy Pan, Ankan Gupta, Koji Foreman, Rahima Zennadi, Kevin R. Rarick, Surya M. Nauli, Sean P. Palacek, Ramani Ramchandran

Pharmacy Faculty Articles and Research

In the developing vasculature, cilia, microtubule-based organelles that project from the apical surface of endothelial cells (ECs), have been identified to function cell autonomously to promote vascular integrity and prevent hemorrhage. To date, the underlying mechanisms of endothelial cilia formation (ciliogenesis) are not fully understood. Understanding these mechanisms is likely to open new avenues for targeting EC-cilia to promote vascular stability. Here, we hypothesized that brain ECs ciliogenesis and the underlying mechanisms that control this process are critical for brain vascular stability. To investigate this hypothesis, we utilized multiple approaches including developmental zebrafish model system and primary cell culture systems. …

Maternal Responses In The Face Of Infection Risk, Patricia C. Lopes, Brenna M. G. Gormally, Aubrey Emmi, Delilah Schuerman, Chathuni Liyanage, Ursula K. Beattie, L. Michael Romero

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When animals are sick, their physiology and behavior change in ways that can impact their offspring. Research is emerging showing that infection risk alone can also modify the physiology and behavior of healthy animals. If physiological responses to environments with high infection risk take place during reproduction, it is possible that they lead to maternal effects. Understanding whether and how high infection risk triggers maternal effects is important to elucidate how the impacts of infectious agents extend beyond infected individuals and how, in this way, they are even stronger evolutionary forces than already considered. Here, to evaluate the effects of …

Effects Of Chronic Stress On Safety Processing And Physiology In The Medial Prefrontal-Amygdala-Basal Forebrain Circuit, Itamar S. Grunfeld

Dissertations, Theses, and Capstone Projects

Chronic stress increases generalization of fear to non-threatening cues, a key symptom in numerous psychiatric mood disorders. However, the mechanisms through which stress impacts safety learning remain poorly understood. To probe the relationship between stress and safety learning, this dissertation employed multiple behaviors, in conjunction with in-vivo multisite physiology during explicit safety and fear discrimination learning. In Chapter 1, I outline the role of chronic stress in driving neurological adaptations that result in generalized fear and highlight how this occurs because of impaired safety cue encoding. In Chapter 2, I show that chronic stress in the form of social defeat …

Female Presence Does Not Increase Testosterone But Still Ameliorates Sickness Behaviours In Male Japanese Quail, Brenna M. G. Gormally, Kaelyn Bridgette, Aubrey Emmi, Delilah Schuerman, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Infections can dramatically modify animal behaviour. The extent of these changes depends on an animal's environment. It has been proposed that testosterone modulates the suppression of behavioural symptoms of sickness under certain reproductive contexts. To further understand the role played by testosterone in modulating sickness behaviours under reproductive contexts, we studied a species, the Japanese quail, in which female exposure rapidly decreases circulating testosterone in males. Males received either an immune challenge (lipopolysaccharide – LPS) or a control injection and their behaviours, mass change and testosterone levels were quantified in the presence or absence of a female. Both the presence …