Activity of the hypothalamic neuropeptide Y increases in adult and decreases in old rats.

Middle-aged obesity and aging anorexia with muscle loss (sarcopenia) of old people present public health burden. These alterations may appear both in humans and rodents suggesting the role for regulatory alterations. Previously, we demonstrated that biphasic changes in the weight-reducing (catabolic) effects of neuropeptides of the hypothalamus-adipose tissue axis (e.

Neuroanatomical evidence and a mouse calcitonin gene-related peptide model in line with human functional magnetic resonance imaging data support the involvement of peptidergic Edinger-Westphal nucleus in migraine.

The urocortin 1 (UCN1)-expressing centrally projecting Edinger-Westphal (EWcp) nucleus is influenced by circadian rhythms, hormones, stress, and pain, all known migraine triggers. Our study investigated EWcp's potential involvement in migraine. Using RNAscope in situ hybridization and immunostaining, we examined the expression of calcitonin gene-related peptide (CGRP) receptor components in both mouse and human EWcp and dorsal raphe nucleus (DRN).

The Lack of TRPA1 Ion Channel Does Not Affect the Chronic Stress-Induced Activation of the Locus Ceruleus.

We have previously proven the involvement of transient receptor potential ankyrin 1 (TRPA1) in stress adaptation. A lack of TRPA1 affects both urocortin 1 (member of the corticotropin-releasing hormone (CRH) family) content of the Edinger-Westphal nucleus. The noradrenergic locus ceruleus (LC) is also an important player in mood control.

Does Preheating Influence the Cytotoxic Potential of Dental Resin Composites?

Resin-based dental composites (RBC) release cytotoxic components, however the extent of the elution from preheated RBCs is barely investigated. The aim was therefore to determine the cytotoxic effect of preheated conventional, bulk, and thermoviscous RBCs of clinically relevant sizes using different cell viability methods in a contact-free model. Samples (6 × 4 mm) were prepared from conventional [Estelite Sigma Quick (ESQ), Filtek Z250 (FZ)] and bulk-filled [Filtek One BulkFill Restorative (FOB), SDR Plus Bulk Flow (SDR), VisCalor Bulk (VCB)] RBCs.

Downregulation of PACAP and the PAC1 Receptor in the Basal Ganglia, Substantia Nigra and Centrally Projecting Edinger-Westphal Nucleus in the Rotenone model of Parkinson's Disease.

Numerous in vitro and in vivo models of Parkinson's disease (PD) demonstrate that pituitary adenylate cyclase-activating polypeptide (PACAP) conveys its strong neuroprotective actions mainly via its specific PAC1 receptor (PAC1R) in models of PD. We recently described the decrease in PAC1R protein content in the basal ganglia of macaques in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD that was partially reversed by levodopa therapy. In this work, we tested whether these observations occur also in the rotenone model of PD in the rat.

Long-term Effects of the pituitary-adenylate cyclase-activating Polypeptide (PACAP38) in the Adult Mouse Retina: Microglial Activation and Induction of Neural Proliferation.

The degenerative retinal disorders characterized by progressive cell death and exacerbating inflammation lead ultimately to blindness. The ubiquitous neuropeptide, PACAP38 is a promising therapeutic agent as its proliferative potential and suppressive effect on microglia might enable cell replacement and attenuate inflammation, respectively. Our previous finding that PACAP38 caused a marked increase of the amacrine cells in the adult (1-year-old) mouse retina, served as a rationale of the current study.

Aging Changes the Efficacy of Central Urocortin 2 to Induce Weight Loss in Rats.

Middle-aged obesity and aging cachexia present healthcare challenges. Central responsiveness to body-weight-reducing mediators, e.g.

A Promising Way to Overcome Temozolomide Resistance through Inhibition of Protein Neddylation in Glioblastoma Cell Lines.

There is no effective therapy for the lately increased incidence of glioblastoma multiforme (GBM)-the most common primary brain tumor characterized by a high degree of invasiveness and genetic heterogeneity. Currently, DNA alkylating agent temozolomide (TMZ) is the standard chemotherapy. Nevertheless, TMZ resistance is a major problem in the treatment of GBM due to numerous molecular mechanisms related to DNA damage repair, epigenetic alterations, cellular drug efflux, apoptosis-autophagy, and overactive protein neddylation.

Absence of Nkx2-3 induces ectopic lymphatic endothelial differentiation associated with impaired extramedullary stress hematopoiesis in the spleen.

The red and white pulps as two main parts of the spleen are arranged around distinct types of vasculature, and perform significantly different functions in both humans and mice. Previous observations indicated a profound alteration of the local vessel specialization in mice lacking Nkx2-3 homeodomain transcription factor, including contradictory results suggesting presence of an ectopic lymphatic vascular structure. Furthermore, how the absence of Nkx2-3 and the consequential changes in endothelial components affect the extramedullary hematopoietic activity restricted to the splenic red pulp is unknown.

Urocortin stimulates the ERK1/2 signaling pathway and the proliferation of HeLa cells via CRF receptor 1.

Corticotropin-releasing factor (CRF) stimulates adrenocorticotropic hormone (ACTH) secretion from the pituitary gland and is an essential regulator of the hypothalamic-pituitary-adrenocortical axis. Isoforms of CRF receptor are known to mediate the effects of urocortin stress ligands on the regulation of stress responses, anxiety, and feeding behavior; however, urocortin stress ligands also influence cell proliferation. In view of the tumor-promoting capacity of prolonged stress, here we investigated (a) the effect of urocortin on cell proliferative signaling via extracellular signal-regulated kinase 1/2, (b) the expression and cellular distribution of the specific CRF receptor isoforms, and (c) the intracellular localization of phosphorylated ERK1/2 in HeLa cells.

Functionally active TRPA1 ion channel is downregulated in peptidergic neurons of the Edinger-Westphal nucleus upon acute alcohol exposure.

The centrally projecting Edinger-Westphal nucleus (EWcp) contributes to the control of alcohol consumption by its urocortin 1 (UCN1) and cocaine- and amphetamine-regulated transcript (CART) co-expressing peptidergic neurons. Our group recently showed that the urocortinergic centrally projecting EWcp is the primary seat of central nervous system transient receptor potential ankyrin 1 (TRPA1) cation channel mRNA expression. Here, we hypothesized that alcohol and its metabolites, that pass through the blood-brain barrier, may influence the function of urocortinergic cells in centrally projecting EWcp by activating TRPA1 ion channels.

Transient receptor potential ankyrin 1 ion channel expressed by the Edinger-Westphal nucleus contributes to stress adaptation in murine model of posttraumatic stress disorder.

The centrally projecting Edinger-Westphal nucleus (EWcp) is involved in stress adaptation. Transient receptor potential ankyrin 1 (TRPA1) mRNA was previously shown to be expressed abundantly in mouse and human EWcp urocortin 1 (UCN1) positive neurons and reacted to chronic stress. Since UCN1 neurons are deeply implicated in stress-related disorders, we hypothesized that TRPA1/UCN1 neurons are also affected in posttraumatic stress disorder (PTSD).

Effect of Pre-Heating on the Monomer Elution and Porosity of Conventional and Bulk-Fill Resin-Based Dental Composites.

The pre-heating of dental resin-based composites (RBCs) improves adaptability to cavity walls, reducing microleakages. However, the rapid cooling of the pre-heated RBC may change the polymerization kinetics, and thus the final network configuration of the RBC. It is well known that unreacted monomers remaining in the set RBC can leach into the oral cavity.

Fluoxetine treatment supports predictive validity of the three hit model of depression in male PACAP heterozygous mice and underpins the impact of early life adversity on therapeutic efficacy.

According to the three hit concept of depression, interaction of genetic predisposition altered epigenetic programming and environmental stress factors contribute to the disease. Earlier we demonstrated the construct and face validity of our three hit concept-based mouse model. In the present work, we aimed to examine the predictive validity of our model, the third willnerian criterion.

Age-Associated B Cell Features of the Murine High-Grade B Cell Lymphoma Bc.DLFL1 and Its Extranodal Expansion in Abdominal Adipose Tissues.

Diffuse large B cell lymphoma comprises a heterogeneous group of B cell-derived tumors, with different degrees of aggressiveness, as defined by their cellular origin and tissue microenvironment. Using the spontaneous Bc.DLFL1 lymphoma originating from a BALB/c mouse as a diffuse large B cell lymphoma model, in this study we demonstrate that the lymphoma cells display surface phenotype, IgH V-region somatic mutations, transcription factor characteristics and in vivo location to splenic extrafollicular regions of age-associated B cells (ABCs), corresponding to T-bet and Blimp-1/CD138 plasmablasts derivation.

Secreted key regulators (Fgf1, Bmp4, Gdf3) are expressed by PAC1-immunopositive retinal ganglion cells in the postnatal rat retina.

Identified as a member of the secretin/glucagon/VIP superfamily, pituitary adenylate cyclase-activating polypeptide (PACAP1-38) has been recognized as a hormone, neurohormone, transmitter, trophic factor, and known to be involved in diverse and multiple developmental processes. PACAP1-38 was reported to regulate the production of important morphogens (Fgf1, Bmp4, Gdf3) through PAC1-receptor in the newborn rat retina. To follow up, we aimed to reveal the identity of retinal cells responsible for the production and secretion of Fgf1, Bmp4, and Gdf3 in response to PACAP1-38 treatment.

Prolonged treatment with the proteasome inhibitor MG-132 induces apoptosis in PC12 rat pheochromocytoma cells.

Rat pheochromocytoma (PC12) cells were treated with the proteasome inhibitor MG-132 and morphological changes were recorded. Initially, neuronal differentiation was induced but after 24 h signs of morphological deterioration became apparent. We performed nuclear staining, flow cytometry and WST-1 assay then analyzed signal transduction pathways involving Akt, p38 MAPK (Mitogen-Activated Protein Kinase), JNK (c-Jun N-terminal Kinase), c-Jun and caspase-3.

Urocortin stimulates ERK1/2 phosphorylation and proliferation but reduces ATP production of MCF7 breast cancer cells.

Urocortins are members of the stress-related corticotropin-releasing factor family. Small amounts of them are present in the circulation and they are produced locally in various tissues of higher vertebrates. Aside from regulating circulation, or food uptake they also influence, via auto- and paracrine mechanisms, cell proliferation.

Neurodegeneration in the centrally-projecting Edinger-Westphal nucleus contributes to the non-motor symptoms of Parkinson's disease in the rat.

Background: The neuropathological background of major depression and anxiety as non-motor symptoms of Parkinson's disease is much less understood than classical motor symptoms. Although, neurodegeneration of the Edinger-Westphal nucleus in human Parkinson's disease is a known phenomenon, its possible significance in mood status has never been elucidated. In this work we aimed at investigating whether neuron loss and alpha-synuclein accumulation in the urocortin 1 containing (UCN1) cells of the centrally-projecting Edinger-Westphal (EWcp) nucleus is associated with anxiety and depression-like state in the rat.

TEGDMA (Triethylene Glycol Dimethacrylate) Induces Both Caspase-Dependent and Caspase-Independent Apoptotic Pathways in Pulp Cells.

Monomers leached from resin-based composites (RBCs) may reach intrapulpal concentrations of the millimolar (mM) range, which could contribute to inflammation. The aim of this investigation was to assess the cytotoxicity of triethylene glycol dimethacrylate (TEGDMA) monomers on pulp cells as well as to identify molecular mechanisms leading to apoptosis. Pulp cells were harvested from molars extracted for orthodontic reasons and cultured through an explant method.

Role of adipose-associated lymphoid tissues in the immunological homeostasis of the serosal surface.

Although not typical lymphoid organs, analysis of the visceral adipose-associated lymphoid tissues has recently substantially expanded our knowledge about the immunological features of these elusive compartments. Recent data have highlighted their considerable complexity in cellular organization and interactions in several biological processes, including adaptive immune responses, tissue plasticity to accommodate mesenchymal stem cells and progenitors, and providing a suitable microenvironment for serosal tumor propagation. This review aims to present a comprehensive view of the adipose-associated lymphoid tissues in local and systemic immune responsiveness, with particular emphasis on the omental and mesenteric lymphoid tissues in the serosal defense of abdominal organs.

Influence of TEGDMA monomer on MMP-2, MMP-8, and MMP-9 production and collagenase activity in pulp cells.

Objectives: Resin-based composites may leach monomers such as triethylene-glycol dimethacrylate (TEGDMA), which could contribute to intrapulpal inflammation. The aim of this investigation was to examine whether various concentrations of TEGDMA are able to influence dentally relevant Matrix metalloproteinase (MMP)-2, MMP-8, and MMP-9 production, total collagenase/gelatinase activity in pulp cells, and suggest possible signaling mechanisms.

Materials And Methods: Pulp cells were cultured, followed by a 1-day exposure to sublethal TEGDMA concentrations (0.

Foliate Lymphoid Aggregates as Novel Forms of Serous Lymphocyte Entry Sites of Peritoneal B Cells and High-Grade B Cell Lymphomas.

The cellular homeostasis of lymphoid tissues is determined by the continuous interactions of mobile hematopoietic cells within specialized microenvironments created by sessile stromal cells. In contrast to the lymph nodes and mucosal lymphoid tissues with well-defined entry and exit routes, the movement of leukocytes in the peritoneal cavity is largely unknown. In this study, we report that, in addition to the omental milky spots and fat-associated lymphoid clusters, in mice, the serous surface of the mesenteric adipose streaks contains lymphocyte-rich organoids comprised of a highly compacted leaf-like part connected to the adipose tissue that can also efficiently bind B cells and high-grade B cell lymphoma (diffuse large B cell lymphoma) cells.

Corticotropin-Releasing Factor-Producing Cells in the Paraventricular Nucleus of the Hypothalamus and Extended Amygdala Show Age-Dependent FOS and FOSB/DeltaFOSB Immunoreactivity in Acute and Chronic Stress Models in the Rat.

Corticotropin-releasing factor (CRF) immunoreactive (ir) neurons of the paraventricular nucleus of the hypothalamus (PVN) play pivotal role in the coordination of stress response. CRF-producing cells in the central nucleus of amygdala (CeA) and oval division of the bed nucleus of stria terminalis (BNSTov) are also involved in stress adaptation and mood control. Immediate early gene products, subunits of the transcription factor activator protein 1 (AP1) are commonly used as acute (FOS) and/or chronic (FOSB/deltaFOSB) markers for the neuronal activity in stress research.