Subregion-specific transcriptomic profiling of rat brain reveals sex-distinct gene expression impacted by adolescent stress.

Stress during adolescence clearly impacts brain development and function. Sex differences in adolescent stress-induced or exacerbated emotional and metabolic vulnerabilities could be due to sex-distinct gene expression in hypothalamic, limbic, and prefrontal brain regions. However, adolescent stress-induced whole-genome expression changes in key subregions of these brain regions were unclear.

A university-wide seed grant program accelerates interprofessional education through faculty and staff engagement.

The University of Texas Health Science Center at San Antonio launched an annual university-wide seed grant program in 2019 to foster innovation in interprofessional education (IPE) and increase IPE opportunities for learners. Program objectives included leveraging hypothesis-driven research to identify sustainable IPE activities for integration into educational programs (i.e.

Current Evidence for Biological Biomarkers and Mechanisms Underlying Acute to Chronic Pain Transition across the Pediatric Age Spectrum.

Chronic pain is highly prevalent in the pediatric population. Many factors are involved in the transition from acute to chronic pain. Currently, there are conceptual models proposed, but they lack a mechanistically sound integrated theory considering the stages of child development.

Innovation in Collaborative Online Learning Yields Sustainable Model for University-wide Interprofessional Education.

Background: Growing health professional accreditation mandates and expectations for interprofessional education (IPE) have led to heightened interest amongst health professions educators and administrators in the creation and development of effective and sustainable IPE programming.

Ipe Activity: At the University of Texas Health Science Center at San Antonio, an institution-wide initiative called Linking Interprofessional Networks for Collaboration (LINC) was initiated to strengthen IPE knowledge and skills, increase IPE offerings, and integrate IPE into curricula. In 2020, stakeholders developed, implemented, and evaluated a university-wide IPE activity called the LINC Common IPE Experience, which includes three collaborative online learning modules that students complete synchronously using a videoconference platform without direct faculty facilitation.

Estrogenic Action in Stress-Induced Neuroendocrine Regulation of Energy Homeostasis.

Estrogens are among important contributing factors to many sex differences in neuroendocrine regulation of energy homeostasis induced by stress. Research in this field is warranted since chronic stress-related psychiatric and metabolic disturbances continue to be top health concerns, and sex differences are witnessed in these aspects. For example, chronic stress disrupts energy homeostasis, leading to negative consequences in the regulation of emotion and metabolism.

Difference in post-stress recovery of the gut microbiome and its altered metabolism after chronic adolescent stress in rats.

The human gut microbiome plays a central role in human health, and has been implicated in the development of a number of chronic gastrointestinal and systemic diseases. For example, microorganisms can serve as microbial endocrine mediators and can respond to stimuli and produce neurochemicals, ultimately influencing the brain-gut-microbiome axis of their host, a bidirectional communication system between the central nervous system and the gastrointestinal tract, especially during developmental stages. To begin to explore potential dynamic changes of the gut microbiome, we characterized gut microbiota in adolescent rats that underwent a fixed period of restraint stress, examined whether the gut microbial population and their metabolic functions were changed by stress, and if such changes during adolescence persist or recover in young adulthood.

Skin tissue dielectric constant in women with high body fat content.

Background: Skin tissue dielectric constant (TDC) measurements at a frequency of 300 MHz are used to assess skin properties in many conditions. Impacts of patient obesity on these values are unknown, and its quantitative assessment was the goal of this research.

Materials And Methods: Women in a weight loss program (N = 32) had TDC measured on forearm, biceps, neck, jowl, and submental regions along with measurements of total body fat (TBF), water (TBW), intracellular water (ICW), and extracellular water (ECW) via multi-frequency bioimpedance.

Differential Sympathetic Activation of Adipose Tissues by Brain-Derived Neurotrophic Factor.

Centrally administered brain-derived neurotrophic factor (BDNF) decreases body adiposity beyond what can be accounted for by decreased food intake, implying enhanced lipid metabolism by BDNF. Consistent with this notion, intracerebroventricular (icv) injection of BDNF in rats increased the expression of lipolytic enzymes in white adipose tissues (WAT) and increased circulating concentrations of lipolytic products without changing the levels of adrenal gland hormones. This suggests that central BDNF-induced lipid mobilization is likely due to sympathetic neural activation, rather than activation of the adrenocortical or adrenomedullary system.

Maintenance of immune tolerance to a neo-self acetylcholine receptor antigen with aging: implications for late-onset autoimmunity.

Age-related changes in immune regulation are likely to account for the age-associated increase in serum autoantibody levels and in certain autoimmune disorders, such as myasthenia gravis (MG). To demonstrate directly a loss of immune tolerance in older individuals, responses to the acetylcholine receptor, the autoantigen in MG, were assessed in transgenic mice expressing the Torpedo californica acetylcholine receptor (TAChR) alpha-chain as a neo-self Ag. T cells from young transgenic mice had been shown to be tolerant to p146-162, the TAChR alpha-chain peptide that dominated young nontransgenic T cell responses in vitro.

IL-4 receptor as a bridge between the immune system and muscle in experimental myasthenia gravis I: up-regulation of muscle IL-15 by IL-4.

The study reported below describes increased expression of IL-4 receptor in cultured rat myocytes following exposure to an antibody reactive with the acetylcholine receptor (AChR). In addition, upon up-regulation of IL-4R, myocytes demonstrated an increased responsiveness to IL-4 by producing increased levels of IL-15. Moreover, following passive transfer of AChR antibody into Lewis rats, both the increased IL-4R expression and IL-15 production were also observed in intact skeletal muscle, co-localizing in particular individual muscle fibers; the same muscle fibers also produced the chemokine MCP-1 to which IL-4-producing T cells were attracted.

Muscle-derived nitric oxide synthase expression, differences associated with muscle fiber-type, and disease susceptibility in a rat model of myasthenia gravis.

Reports from this laboratory suggested that expression of skeletal muscle-derived, inducible nitric oxide synthase (iNOS), is associated with resistance of a particular rat strain to the autoimmune model of myasthenia gravis (MG). The study reported below demonstrates a similar association between iNOS induction in skeletal muscle and disease-resistance when comparing different skeletal muscles originating from the same rat strain. Thus, soleus muscles, shown previously to be relatively resistant to disease even when obtained from disease-susceptible Lewis rats, were observed to express high levels of iNOS following exposure to antibody reactive with the nicotinic acetylcholine receptor (AChR).

Short-circuiting autoimmune disease by target-tissue-derived nitric oxide.

A previous report from this laboratory suggested that expression of skeletal-muscle-derived, inducible nitric oxide synthase (iNOS), is associated with resistance to the autoimmune model of myasthenia gravis (MG) demonstrated by Wistar Furth rats following the passive transfer of antibody reactive with the nicotinic acetylcholine receptor (AChR). The study reported below demonstrates an association between increased expression of iNOS/NO in Wistar Furth rats and the induction of programmed cell death (apoptosis) in both macrophages and CD4+ T cells that attempt to traffic through targeted muscles. It is concluded that production of muscle-derived NO is protective in experimental MG, and in part, dictates the severity of eventual immunopathology.

Recall immune memory: a new tool for generating late onset autoimmune myasthenia gravis.

Most patients with autoimmune myasthenia gravis (MG) produce autoantibodies against their muscle acetylcholine receptors (AChR), causing debilitating muscle weakness. Approximately 60% of MG patients first exhibit myasthenic symptoms after the age of 40. Yet, in the C57BL/6 mouse model of MG, older mice are resistant to induction of myasthenia gravis.

Myocyte production of nitric oxide in response to AChR-reactive antibodies in two inbred rat strains may influence disease outcome in experimental myasthenia gravis.

In an attempt to identify mechanisms that explain the difference in susceptibility of two rat strains to the induction of experimental autoimmune myasthenia gravis (EAMG), acetylcholine receptor (AChR)-reactive antibodies were tested for their ability to up-regulate levels of inducible nitric oxide synthase (iNOS) in skeletal muscles of disease-sensitive Lewis rats and disease-resistant Wistar Furth (WF) rats. Initially, the WF muscle cell line, WE1, appeared to be more sensitive to antibody-stimulated iNOS induction and NO production than did the Lewis muscle cell line, LE1. Next, AChR-reactive antibody induced widespread iNOS production in skeletal muscles of WF rats, while iNOS production in muscles of Lewis rats was much less pronounced.

Split tolerance in a novel transgenic model of autoimmune myasthenia gravis.

Because it is one of the few autoimmune disorders in which the target autoantigen has been definitively identified, myasthenia gravis (MG) provides a unique opportunity for testing basic concepts of immune tolerance. In most MG patients, Abs against the acetylcholine receptors (AChR) at the neuromuscular junction can be readily identified and have been directly shown to cause muscle weakness. T cells have also been implicated and appear to play a role in regulating the pathogenic B cells.

Muscle responds to an antibody reactive with the acetylcholine receptor by up-regulating monocyte chemoattractant protein 1: a chemokine with the potential to influence the severity and course of experimental myasthenia gravis.

Autoantibodies with reactivity against the postjunctional muscle receptor for acetylcholine receptor are able to interfere with contractile function of skeletal muscles and cause the symptoms of myasthenia gravis (MG) in humans, as well as in experimental animal models of MG. In the study described below using a rat model of MG, it was observed that exposure to acetylcholine receptor-reactive Abs also induced increased levels of chemokine (i.e.

Immunological memory and late onset autoimmunity.

This review will address a paradox that has long fascinated scientists studying the effects of aging on the immune system. Although it has been clearly documented that B and T lymphocytes lose the ability to respond to antigenic or mitogenic stimulation with age, it has nonetheless been noted that the frequency of autoreactive antibodies is higher in older individuals. Given that the majority of the age-associated defects in immune regulation target the naïve T and B lymphocyte subsets, it has been presumed that this increase in antibodies specific for self antigens was due to changes in the B cell repertoire and/or to differences in the mechanisms responsible for generating immune tolerance in primary responses.

Acetylcholine receptor-reactive antibody induces nitric oxide production by a rat skeletal muscle cell line: influence of cytokine environment.

The monoclonal Lewis rat skeletal muscle cell line, LE1, responded to the acetylcholine receptor (AChR)-reactive antibody mAb35 by up-regulating levels of mRNA for inducible nitric oxide synthase (iNOS/NOS-II), followed by levels of NO. Interferon-gamma (IFN-gamma) and interleukin-1 (IL-1) were also each capable of inducing iNOS message, and synergistically with mAb35. Finally, myocyte-derived NO was implicated as a possible source of immunomodulation in experimental autoimmune myasthenia gravis (EAMG), as shown by the ability of the culture fluids from IFN-gamma-activated LE1 cells to inhibit the proliferation of AChR-reactive T cells.

Myocytes respond in vivo to an antibody reactive with the acetylcholine receptor by upregulating interleukin-15: an interferon-gamma activator with the potential to influence the severity and course of experimental myasthenia gravis.

The monoclonal antibody, mAb35, which binds the main immunogenic region of the post-junctional muscle receptor for acetylcholine (AChR), results in contractile dysfunction and symptoms of experimental myasthenia gravis (EAMG). As described below, exposure to mAb35 also results in the production by muscle of increased levels of the interferon-gamma (IFN-gamma)-activating cytokine, interleukin-15. This effect is accompanied by the increased trafficking of leukocytes through muscle, some that produce IFN-gamma.

Characterization of human anti-acetylcholine receptor monoclonal autoantibodies from the peripheral blood of a myasthenia gravis patient using combinatorial libraries.

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against the nicotinic acetylcholine receptor (AChR). Using phage-display technology we have characterized the largest panel of anti-AChR monoclonal antibodies thus far isolated from a single patient. Despite having been isolated with either Torpedo AChR or a human peptide, the recombinant antibodies shared with the donor's serum the ability to recognize human AChR expressed in its native configuration on the surface of TE671 cells.

Myocytes respond to both interleukin-4 and interferon-gamma: cytokine responsiveness with the potential to influence the severity and course of experimental myasthenia gravis.

Messenger RNA that encodes for interleukin-15 (IL-15) has been reported to be constitutively expressed in skeletal muscle, although the protein product is not generally observed. Furthermore, interferon-gamma (IFN-gamma) has been reported to exacerbate symptoms of experimental myasthenia gravis (EAMG). Therefore, since IL-15 is an activator of IFN-gamma-producing cells, the hypothesis that drove the study reported below proposes that muscle is not a passive participant in the development of disease symptoms in EAMG and, in fact, plays a very important active role by producing immunomodulating factors that can influence the eventual immunopathological impact of the immune system on muscle.

A monoclonal lewis rat myocyte line that responds to interferon-gamma: responsiveness with the potential to influence subsequent interactions with the immune system.

In order to begin asking questions about immunopathology associated with the model of the neuromuscular disease experimental autoimmune myasthenia gravis, a monoclonal myocyte line, LE1, has been prepared from the Lewis rat. The LE1 myocyte clone was selected from among several clones produced based on its ease of maintenance in culture and for the stability of its phenotype, which is very similar to that reported for in vivo muscle and other cultured myocyte lines. Thus, LE1 cells were observed to produce, constitutively, the myocyte-associated neural cell adhesion molecule (CD56), the intracellular adhesion molecule (ICAM-1), and the acetylcholine receptor.

Chemokine production by rat myocytes exposed to interferon-gamma.

Messenger RNA that encodes for monocyte chemotactic protein-1 (MCP-1), as well as its protein product, was observed to be constitutively expressed at low levels in a monoclonal Lewis rat skeletal muscle cell line (LE1). Immunohistochemical analyses of sections of skeletal muscle yielded similar results. Since interferon-gamma (IFN-gamma) has been reported to have a likely role in determining the severity of symptoms in the neuromuscular autoimmune disease experimental myasthenia gravis (EAMG), the hypothesis tested and proven true in these studies was that IFN-gamma would up-regulate the production of MCP-1 in LE1 cells.