Neuroendocrine Activity Research Articles

Stress responses in captive Crocodylus moreletii associated with metal exposure

Environmental pollution by metals has repercussions on wildlife health. It is known that some metals can have an influence on the neuroendocrine stress response, and at the same time, metals have pro-oxidant effects that can overwhelm the antioxidant system and cause oxidative stress. This study evaluates the association of metals with neuroendocrine stress activity and biomarkers of oxidative stress in 42 captive female Morelet's crocodiles (Crocodylus moreletii). We measured five metals of ecotoxicological importance (Hg, Cd, Pb, Cu and Zn), and three biomarkers of the oxidative stress response in the liver: glutathione (GSH) and glutathione disulfide (GSSG) as markers for antioxidant system and thiobarbituric acid reactive substances (TBARS) for oxidative damage. We also measured one biomarker of the neuroendocrine response to stress: corticosterone (B) in blood plasma. The mean ± SD concentrations of metals in the liver expressed in μg/g (dw) were: Cd: 0.004 ± 0.003, Hg: 0.014 ± 0.019, Cu: 0.017 ± 0.013, Zn: 0.043 ± 0.035, Pb: 0.16 ± 0.256. The mean ± SD of GSH was 0.42 ± 0.35 nmol/mg protein, the mean ± SD of GSSG was 0.24 ± 0.20 nmol/mg protein, the mean ± SD concentrations of TBARS were 0.36 ± 0.21 nmol/mg protein, and the mean ± SD of B was 393.57 ± 405.14 pg/mL. Hg presented a significant negative relationship with corticosterone. Cd had a negative relationship with both GSH and GSSG; meanwhile, Zn showed a negative relationship with TBARS levels, could be a protective element against hepatic oxidative damage. Finally, B had negative relationship with oxidative damage. The connection found between Hg and the neuroendocrine stress response, as well as the correlations of Cd and Zn with oxidative damage and antioxidant activity should be studied further, given their toxicological importance and implications for the conservation of C. moreletii and other crocodilians.

Abstract 989: Spatial profiling of androgen receptor splice variant 7 transcriptional activity in prostate cancer metastases

Abstract Introduction: Androgen receptor splice variant 7 (AR-V7) is expressed in metastases from patients with castration resistant prostate cancer (CRPC) and shows a high level of inter- and intra-tumoral variability. However, the downstream activity generated by AR-V7 in tissue has not been shown. Whether AR-V7 is active in tissue or whether AR-V7 is a non-functioning biomarker with full-length AR is not known. To address this question, we constructed a tissue microarray (TMA) of 56 metastases from 27 patients with CRPC to analyze spatial gene expression using the GeoMx Digital Spatial Profiler. Immunostaining was performed to define epithelial, vascular, and stromal compartments. The stained tissues were then hybridized with barcoded tagged oligonucleotides targeting 2093 unique genes, which included those representing AR, AR-V cryptic exons, AR and neuroendocrine activity, and immune cell markers. One 500 um region of interest (ROI) was assessed per tissue core (approximately 1200 cells). A sequential section from the same TMA was then stained with AR-V7 and AR-C-terminal specific antibodies. ROIs for RNA and protein were selected to be similar between slides. In addition to DSP, each metastasis was assessed by RNA-seq on the bulk tissue. Results: The most differentially expressed genes (FDR<0.05) based on association with AR-V7 staining were known downstream AR regulated genes including KLK2 and 3, FKBP5, NKX3.1, TMPRSS2, FASN, and TARP. Additionally, genes associated with proliferation and stemness, e.g., POLB, KRT1, SOX2, were significantly expressed. Since 93% of patients were on ADT at time of tissue collection and over 80% also had been treated with either abiraterone or enzalutamide, the increase in AR downstream genes would not be expected to occur from ligand activation of AR-FL. We also have previously shown that knock-down of AR-V7 in LNCaP95 cells results in loss of AR binding to AREs. In these metastases, then, activation of AR downstream genes would be a result of AR-V7 nuclear transport of AR-FL through AR-V7/AR-FL heterodimers or transcriptional activation by AR-V7 homodimers. Of further note, AR cryptic exons 1, 2, and 5 were also significantly expressed in AR-V7 positive ROIs (p< 0.0001). RNA-seq intron/exon junction reads were used to demonstrate that additional AR-Vs, most commonly AR-V9, were also expressed in tissues positive for AR-V7, suggesting that AR splicing is a common event in CRPC. Finally, expression of neuroendocrine (NE) genes INSM1 and TUBB2 were not expressed in AR-V7 positive ROIs (negatively correlated, p<0.001), indicating that AR-V7 and NE phenotypes cannot co-exist in the same cell. Conclusion: AR-V7 continues to drive prostate cancer through activation of the AR-cistrome. Its expression is heterogenous in metastases along with NE cells, suggesting that in the presence of AR-V7 and NE markers, therapy needs to be directed at the N-terminus of AR and NE components. Citation Format: Cynthia C. Sprenger, Ilsa Coleman, Michelle Kriner, Lauren Brady, Margaret Hoang, Martine Roudier, Mamatha Damodarasamy, Radhika Patel, Lawrence True, Peter Nelson, Michael Haffner, Stephen Plymate. Spatial profiling of androgen receptor splice variant 7 transcriptional activity in prostate cancer metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 989.

Role of autonomous and endocrine factors in immunotropic effects of nitrogenous metabolites in patients with chronic pyelonephritis

Background. We have previously shown that nitrogenous metabolites have immunomodulatory effects in healthy rats and humans as well as patients with dysfunction of neuroendocrine-immune complex, encephalopatia and chronic pyelonephritis. The purpose of this study is clarification of the role of neuro-endocrine factors in their immunotropic activity in patients with chronic pyelonephritis. Materials and Methods. The object of observation were 17 men (aged 24-70 years) with chronic pyelonephritis in remission. The plasma levels and urinary excretion of nitrogenous metabolites as well as parameters of immunity and its neuro-endocrine regulation twice (on admission and after balneotherapy at the Truskavets’ Spa) was performed. Results. Judging by the multiple correlation coefficient, uricosuria exhibits maximal neuro-endocrine activity (R=0,780), followed by bilirubinemia (R=0,742), creatinineuria (R=0,692), uricemia (R=0,636), creatinineemia (R=0,632), urea excretion (R=0,536), instead urea plasma correlate with neuro-endocrine parameters insignificantly (R=0,360). Nitrogenous metabolites together determine the state of neuro-endocrine regulation by 94,2%, which, in turn, determine the state of immunity by 99,9%. Conclusion. Nitrogenous metabolites carry out immunomodulation in different ways: directly through aryl hydrocarbon (bilirubin), toll-like and adenosine (uric acid) receptors of immunocytes; through modulation of the activity of neurons of the autonomous nervous system and endocrinocytes with subsequent neuro-endocrine immunomodulation; and also, apparently, due to an off-receptor effect on neurons, endocrinocytes and immunocytes (urea and creatinine).

Antibiotics Alter the Expression of Genes Related to Behavioral Development in Honey Bees (Hymenoptera: Apidae).

Honey bees, as many species of social insects, display a division of labor among colony members based on behavioral specializations related to age. Adult worker honey bees perform a series of tasks in the hive when they are young (such as brood care or nursing) and at ca. 2–3 wk of age, shift to foraging for nectar and pollen outside the hive. The transition to foraging involves changes in metabolism and neuroendocrine activities. These changes are associated with a suite of developmental genes. It was recently demonstrated that antibiotics influence behavioral development by accelerating or delaying the onset of foraging depending on timing of antibiotic exposure. To understand the mechanisms of these changes, we conducted a study on the effects of antibiotics on expression of candidate genes known to regulate behavioral development. We demonstrate a delay in the typical changes in gene expression over the lifetime of the individuals that were exposed to antibiotics during immature stage and adulthood. Additionally, we show an acceleration in the typical changes in gene expression on individuals that were expose to antibiotics only during immature stage. These results show that timing of antibiotic exposure alter the typical regulation of behavioral development by metabolic and neuroendocrine processes.

Regulation of the gonadotropin-releasing hormone neuron during stress.

The effect of stress on reproduction and gonadal function has captivated investigators for almost 100years. Following the identification of gonadotropin-releasing hormone (GnRH) 50years ago, a niche research field emerged fixated on how stress impairs this central node controlling downstream pituitary and gonadal function. It is now clear that both episodic GnRH secretion in males and females and surge GnRH secretion in females are inhibited during a variety of stress types. There has been considerable advancement in our understanding of numerous stress-related signaling molecules and their ability to impair reproductive neuroendocrine activity during stress. Recently, much attention has turned to the effects of stress on two populations of kisspeptin neurons: the stimulatory afferents to GnRH neurons that regulate pulsatile and surge-type gonadotropin secretion. Indeed, future work is still required to fully construct the neuroanatomical framework underlying stress effects, directly or indirectly, on GnRH neuron function. The present review evaluates and synthesizes evidence related to stress-related signaling molecules acting directly on GnRH neurons. Here, we review the evidence for and against the action of a handful of signaling molecules as inhibitors of GnRH neuron function, including corticotropin-releasing hormone, urocortins, norepinephrine, cortisol/corticosterone, calcitonin gene-related peptide and arginine-phenylalanine-amide-related peptide-3.

The power of the citizen in digital culture.

Symptoms reported by the patient are generally considered to be of lesser scientific value than objective, measurable data. New digital technologies make it possible to record sensations that have always been expressed through the lens of subjectivity, such as mood, cognitive activity and neuroendocrine activity. The patient's access to biological and behavioral parameters and the possibility of acquiring them directly, independently and autonomously, allow people to actively participate in their own care process and in maintaining their state of health, capable of balancing and sometimes overturning the traditional top-down relationship with the doctor. The downside is a medical culture increasingly oriented towards the measurement of health and well-being, while clinical experience teaches that taking care of people must include a global approach, focused on the identification and sharing of values, meaning, interests, dimensions that are difficult to measure.

Neuroendocrine and autonomic stress systems activity in young adults raised by mothers with mental health and substance abuse problems: A prospective cohort study.

Among the well-known physiological consequences of early adverse environments is dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. A number of studies demonstrate that negative parenting and living with parents with a history of substance abuse and mental health problems may be associated with HPA axis dysregulation in children. In contrast, studies of more delayed effects in adult offspring, especially prospective, are still scarce. This study was a prospective longitudinal investigation of the association between maternal mental illnesses/substance abuse and maternal negative parenting/parental stress on one side and, on the other side, adult offspring outcomes 10 years later-specifically, we studied the activity of offspring's neuroendocrine (cortisol) and autonomic (heart rate) systems when exposed to a mild psychological stressor. Children of mothers with mental illnesses and/or substance abuse were exposed to more disadvantaged conditions (higher negative parenting and community violence). Despite this, maternal risk groups (having a mother with mental illnesses and/or substance abuse) were not associated with any of the indicators of stress systems activity. Regardless of the risk group, participants with dysregulated HPA axis activity experienced a higher level of negative parenting. Altogether, our study provides evidence that negative parenting may have long-lasting effects on stress-sensitive physiological mechanisms.

Neurophysiological Correlates of Sensory-Based Phenotypes in ASD.

Children with autism spectrum disorder frequently present with atypical behavioral responses to sensory stimuli, as well as differences in autonomic nervous system (ANS) and neuroendocrine activity. However, no one consistent pattern appears to explain these differences within this heterogeneous population. To conceptualize more homogenous ASD subgroups, sensory-based subtypes have been explored. One subtyping mechanism groups children by sensory responsivity pattern in addition to sensory domain. Differences in nervous system responsivity to sensory input within this sensory-based subtyping scheme have not yet been investigated. This exploratory study used ANS indices (respiratory sinus arrhythmia [RSA], skin conductance level) and neuroendocrine (salivary cortisol) response to examine patterns differentiating these subtypes. Significant differences in RSA were found during baseline, and during tactile, tone and movement stimuli (p < 0.05). Subtype membership was predicted by RSA changes during auditory stimulation and recovery periods (p < 0.05). Results confirm that children with an adaptive sensory responsivity subtype differ from those children with sensory processing dysfunction, however, physiological variables did not distinguish between children with different patterns of sensory processing dysfunction.

Pan-cancer analyses reveal genomics and clinical characteristics of the melatonergic regulators in cancer.

Melatonin, an endogenous hormone, plays protective roles in cancer. In addition to regulating circadian rhythms, sleep, and neuroendocrine activity, melatonin functions in various survival pathways. However, the mechanisms of melatonin regulation in cancer remain unknown. In the present study, we performed a comprehensive characterization of melatonin regulators in 9125 tumor samples across 33 cancer types using multi-omic data from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia. In the genomic landscape, we identified the heterozygous amplification of AANAT and GPR50, and heterozygous deletion of PER3, CYP2C19, and MTNR1A as the dominant alteration events. Expression analysis revealed methylation-mediated downregulation of melatonergic regulator expression. In addition, we found that melatonergic regulator expression could be used to predict patient survival in various cancers. In depth, microRNA (miRNA) analysis revealed an miRNA-mRNA interaction network, and the deregulated miRNAs were involved in melatonin secretion and metabolism by targeting circadian clock genes. Pathway analysis showed that melatonergic regulators were associated with inhibition of apoptosis, the cell cycle, the DNA damage response, and activation of RAS/MAPK and RTK signaling pathways. Importantly, by mining the Genomics of Drug Sensitivity in Cancer database, we discovered a number of potential drugs that might target melatonergic regulators. In summary, this study revealed the genomic alteration and clinical characteristics of melatonergic regulators across 33 cancers, which might clarify the relationship between melatonin and tumorigenesis. Our findings also might provide a novel approach for the clinical treatment of cancers.

Neuroendocrine and Cardiovascular Activation During Aggressive Reactivity in Dogs.

Our aim was to investigate cardiovascular activation by measuring changes in facial and body surface temperature using infrared thermography, and neuroendocrine activation using salivary cortisol (CORT) and serotonin concentration (SER) in dogs exhibiting aggressive reactivity in real time. Based on two factors, owner-reported past aggressive behaviors, and detailed behavioral observations collected during a Socially Acceptable Behavior test consisting of 16 subtests and, each individual was categorized as aggressive or non-aggressive. CORT and SER showed no difference in neuroendocrine activity between dogs, but aggressive dogs with higher levels of aggression were found to have lower SER. Aggressive dogs also had an increase in facial temperature from pre-test values. The discovery of a correlation between tail wagging and left tail wagging with aggression level and aggression-related behaviors in aggressive dogs is further evidence of the right hemisphere specialization for aggression previously reported in the literature. This study provides the first evidence that both cardiovascular and neuroendocrine systems are activated during an active act of aggression in dogs.

Myocardial perfusion SPECT as a potential mediator on circulating chromogranin A in patients with old myocardial infarction.

Chromogranin A (CgA) is a soluble polypeptide stored within and released from secretory granules of endocrine and other cell types (including cardiomyocytes); CgA appears to be a marker of the overall neuroendocrine activity. Increased levels of serum CgA have been found not only in patients with neuroendocrine neoplasms but also with other malignancies, hypertension, myocardial infarction, heart, or renal failure. A population of 307 patients (202 males, 105 females) was enrolled. The study group consisted of 118 individuals (38.4%) with myocardial infarction more than one year old (MI group); the remaining 189 (61.6%) had no known heart disease (control group). All patients underwent myocardial perfusion scintigraphy (MPS) after blood withdrawal for serum CgA measurement. To test whether a possible effect of old infarction on serum CgA is mediated by MPS findings, we employed analysis of covariance for three distinct categories of left ventricular (LV) perfusion deficits as dichotomous predictors: (1) any-type deficits (abnormal MPS); (2) reversible deficits (ischemia); and (3) fixed deficits (scar). In all three MPS conditions, the effect of age, gender, and LV ejection fraction (EFLV) on serum CgA was statistically significant: women exhibited higher CgA levels than men (P=0.008-0.023), whereas increasing age and decreasing EFLV were associated with increasing CgA (all P<0.001). Conversely, no statistically significant differences in mean CgA levels were found between MI patients and normal controls with either abnormal MPS, scar, or ischemia, or their degree and extent. Although serum CgA is significantly associated with age, gender, and EFLV in patients with an old MI, no association was found between CgA levels and either old MI history or MPS findings. The verified involvement of circulating CgA in the acute/subacute phase of infarction appears to be blunted in infarctions older than a year.

Ethnic-Racial discrimination experiences predict Latinx adolescents’ physiological stress processes across college transition

Consistent with conceptual frameworks of ethnic-race-based stress responses, and empirical evidence for the detrimental effects of ethnic-racial discrimination, the current study hypothesized that experiencing more frequent ethnic-racial discrimination during adolescence would predict differences in physiological responses to psychosocial stress across the college transition. U.S. Latinx adolescents (N=84; Mage =18.56; SD=0.35; 63.1% female; 85.7% Mexican descent) completed survey measures of ethnic-racial discrimination during their final year of high school and first college semester (~5 months later), as well as a standard psychosocial stressor task during their first college semester. Repeated blood pressure and salivary cortisol measures were recorded to assess cardiovascular and neuroendocrine activity at baseline and stress reactivity and recovery. Data were analyzed using multilevel growth models. Experiencing more frequent ethnic-racial discrimination in high school, specifically from adults, predicted higher baseline physiological stress levels and lower reactivity to psychosocial stress during the first college semester, evidenced by both blood pressure and cortisol measures. Experiencing ethnic-racial discrimination from peers in high school also predicted higher baseline blood pressure in college, but not stress reactivity indices. Results were consistent when controlling for concurrent reports of ethnic-racial discrimination, gender, parents' education level, body mass index, oral contraceptive use, time between longitudinal assessments, depressive symptoms, and general perceived stress. Experiencing frequent ethnic-racial discrimination during adolescence may lead to overburdening stress response systems, indexed by lower cardiovascular and neuroendocrine stress reactivity. Multiple physiological stress systems are sensitive to the consequences of ethnic-racial discrimination among Latinx adolescents transitioning to college.

Galaxolide and tonalide modulate neuroendocrine activity in marine species from two taxonomic groups

Galaxolide (HHCB) and tonalide (AHTN) are polycyclic musk compounds (PMCs) used in household and personal care products that have been included on the list as emerging contaminants of environmental concern due to their ubiquity in aquatic and terrestrial environments. There still exists a dearth of information on the neurotoxicity and endocrine disrupting effects of these contaminants, especially for marine and estuarine species. Here, we assessed the neuroendocrine effects of HHCB and AHTN using adult clams, Ruditapes philippinarum, and yolk-sac larvae of sheepshead minnow, Cyprinodon variegatus. The clams were treated with concentrations (0.005–50 μg/L) of each compound for 21 days. Meanwhile, sheepshead minnow larvae were exposed to 0.5, 5 and 50 μg/L of HHCB and AHTN for 3 days. Enzyme activities related to neurotoxicity (acetylcholinesterase - AChE), neuroendocrine function (cyclooxygenase - COX), and energy reserves (total lipids - TL) were assessed in R. philippinarum. Gene expression levels of cyp19 and vtg1 were measured in C. variegatus using qPCR. Our results indicated induction of AChE and COX in the clams exposed to HHCB while AHTN exposure significantly inhibited AChE and COX. Gene expression of cyp19 and vtg1 in yolk-sac C. variegatus larvae exposed to 50 μg/L AHTN was significantly downregulated versus the control. The results of this study demonstrate that HHCB and AHTN might pose neurotoxic and endocrine disrupting effects in coastal ecosystems.

Inter- and intra-tumor heterogeneity of metastatic prostate cancer determined by digital spatial gene expression profiling

Metastatic prostate cancer (mPC) comprises a spectrum of diverse phenotypes. However, the extent of inter- and intra-tumor heterogeneity is not established. Here we use digital spatial profiling (DSP) technology to quantitate transcript and protein abundance in spatially-distinct regions of mPCs. By assessing multiple discrete areas across multiple metastases, we find a high level of intra-patient homogeneity with respect to tumor phenotype. However, there are notable exceptions including tumors comprised of regions with high and low androgen receptor (AR) and neuroendocrine activity. While the vast majority of metastases examined are devoid of significant inflammatory infiltrates and lack PD1, PD-L1 and CTLA4, the B7-H3/CD276 immune checkpoint protein is highly expressed, particularly in mPCs with high AR activity. Our results demonstrate the utility of DSP for accurately classifying tumor phenotype, assessing tumor heterogeneity, and identifying aspects of tumor biology involving the immunological composition of metastases.

Intranasal insulin.

The intranasal (IN) route enables the delivery of insulin to the central nervous system in the relative absence of systemic uptake and related peripheral side effects. Intranasally administered insulin is assumed to travel along olfactory and adjacent pathways and has been shown to rapidly accumulate in cerebrospinal fluid, indicating efficient transport to the brain. Two decades of studies in healthy humans and patients have demonstrated that IN insulin exerts functional effects on metabolism, such as reductions in food intake and body weight and improvements of glucose homeostasis, as well as cognition, ie, enhancements of memory performance both in healthy individuals and patients with mild cognitive impairment or Alzheimer's disease; these studies moreover indicate a favourable safety profile of the acute and repeated use of IN insulin. Emerging findings suggest that IN insulin also modulates neuroendocrine activity, sleep-related mechanisms, sensory perception and mood. Some, but not all studies point to sex differences in the response to IN insulin that need to be further investigated along with the impact of age. "Brain insulin resistance" is an evolving concept that posits impairments in central nervous insulin signalling as a pathophysiological factor in metabolic and cognitive disorders such as obesity, type 2 diabetes and Alzheimer's disease, and, notably, a target of interventions that rely on IN insulin. Still, the negative outcomes of longer-term IN insulin trials in individuals with obesity or Alzheimer's disease highlight the need for conceptual as well as methodological advances to translate the promising results of proof-of-concept experiments and pilot clinical trials into the successful clinical application of IN insulin.

Differential Level of RXFP3 Expression in Dopaminergic Neurons Within the Arcuate Nucleus, Dorsomedial Hypothalamus and Ventral Tegmental Area of RXFP3-Cre/tdTomato Mice.

RXFP3 (relaxin-family peptide 3 receptor) is the cognate G-protein-coupled receptor for the neuropeptide, relaxin-3. RXFP3 is expressed widely throughout the brain, including the hypothalamus, where it has been shown to modulate feeding behavior and neuroendocrine activity in rodents. In order to better characterize its potential mechanisms of action, this study determined whether RXFP3 is expressed by dopaminergic neurons within the arcuate nucleus (ARC) and dorsomedial hypothalamus (DMH), in addition to the ventral tegmental area (VTA). Neurons that express RXFP3 were visualized in coronal brain sections from RXFP3-Cre/tdTomato mice, which express the tdTomato fluorophore within RXFP3-positive cells, and dopaminergic neurons in these areas were visualized by simultaneous immunohistochemical detection of tyrosine hydroxylase-immunoreactivity (TH-IR). Approximately 20% of ARC neurons containing TH-IR coexpressed tdTomato fluorescence, suggesting that RXFP3 can influence the dopamine pathway from the ARC to the pituitary gland that controls prolactin release. The ability of prolactin to reduce leptin sensitivity and increase food consumption therefore represents a potential mechanism by which RXFP3 activation influences feeding. A similar proportion of DMH neurons containing TH-IR expressed RXFP3-related tdTomato fluorescence, consistent with a possible RXFP3-mediated regulation of stress and neuroendocrine circuits. In contrast, RXFP3 was barely detected within the VTA. TdTomato signal was absent from the ARC and DMH in sections from Rosa26-tdTomato mice, suggesting that the cells identified in RXFP3-Cre/tdTomato mice expressed authentic RXFP3-related tdTomato fluorescence. Together, these findings identify potential hypothalamic mechanisms through which RXFP3 influences neuroendocrine control of metabolism, and further highlight the therapeutic potential of targeting RXFP3 in feeding-related disorders.

Astroglial Regulation of Magnocellular Neuroendocrine Cell Activities in the Supraoptic Nucleus.

Studies on the interactions between astrocytes and neurons in the hypothalamo-neurohypophysial system have significantly facilitated our understanding of the regulation of neural activities. This has been exemplified in the interactions between astrocytes and magnocellular neuroendocrine cells (MNCs) in the supraoptic nucleus (SON), specifically during osmotic stimulation and lactation. In response to changes in neurochemical environment in the SON, astrocytic morphology and functions change significantly, which further modulates MNC activity and the secretion of vasopressin and oxytocin. In osmotic regulation, short-term dehydration or water overload causes transient retraction or expansion of astrocytic processes, which increases or decreases the activity of SON neurons, respectively. Prolonged osmotic stimulation causes adaptive change in astrocytic plasticity in the SON, which allows osmosensory neurons to reserve osmosensitivity at new levels. During lactation, changes in neurochemical environment cause retraction of astrocytic processes around oxytocin neurons, which increases MNC's ability to secrete oxytocin. During suckling by a baby/pup, astrocytic processes in the mother/dams exhibit alternative retraction and expansion around oxytocin neurons, which mirrors intermittently synchronized activation of oxytocin neurons and the post-excitation inhibition, respectively. The morphological and functional plasticities of astrocytes depend on a series of cellular events involving glial fibrillary acidic protein, aquaporin 4, volume regulated anion channels, transporters and other astrocytic functional molecules. This review further explores mechanisms underlying astroglial regulation of the neuroendocrine neuronal activities in acute processes based on the knowledge from studies on the SON.

Vagotomy Affects Lipopolysaccharide-Induced Changes of Urocortin 2 Gene Expression in the Brain and on the Periphery.

The corticotropin-releasing hormone family of peptides is involved in regulating the neuroendocrine stress response. Also, the vagus nerve plays an important role in the transmission of immune system-related signals to brain structures, thereby orchestrating the neuroendocrine stress response. Therefore, we investigated gene expression of urocortin 2 (Ucn2) and c-fos, a markers of neuronal activity, within the hypothalamic paraventricular nucleus (PVN), a brain structure involved in neuroendocrine and neuroimmune responses, as well as in the adrenal medulla and spleen in vagotomized rats exposed to immune challenge. In addition, markers of neuroendocrine stress response activity were investigated in the adrenal medulla, spleen, and plasma. Intraperitoneal administration of lipopolysaccharide (LPS) induced a significant increase of c-fos and Ucn2 gene expression in the PVN, and adrenal medulla as well as increases of plasma corticosterone levels. In addition, LPS administration induced a significant increase in the gene expression of tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) in the adrenal medulla. In the spleen, LPS administration increased gene expression of c-fos, while gene expression of TH and PNMT was significantly reduced, and gene expression of Ucn2 was not affected. Subdiaphragmatic vagotomy significantly attenuated the LPS-induced increases of gene expression of c-fos and Ucn2 in the PVN and Ucn2 in the adrenal medulla. Our data has shown that Ucn2 may be involved in regulation of the HPA axis in response to immune challenge. In addition, our findings indicate that the effect of immune challenge on gene expression of Ucn2 is mediated by vagal pathways.

The impact of citicoline on brain injury in rats subjected to head irradiation.

Hazard and risk associated with the use of radiotherapy play a crucial role in brain injury with interference via the neuroendocrine activity of the cancer survivors, and there is no effective preventive strategy. We conducted this study to assess the effect of citicoline in biosynthesis variants occurring in the cerebral cortex of rats in response to head γ-irradiation. Bio-analysis includes MDA, 8-OHdG, and NO as oxidation indicators; total antioxidant activity; the inflammatory factors TNF-α, IL-1β, and amyloid-β 42 levels; the caspase-3 cell death marker; IGF-I; serum hormones including GH, ACTH, FSH, and LH; and the neurotransmitters acetylcholine, dopamine, and serotonin. We exposed animals to 10Gy head gamma irradiation followed by citicoline treatment and sustained for 30days. The animals were sacrificed at the 3rd and 30th day post-irradiation. Citicoline mechanism has been linked to potent radical reduced ability counteracting the oxidative stress-mediated inflammation and apoptosis. Citicoline treatment has normalized the altering recorded in serum hormones associated with a significant modulation in the levels of IGF-1/PI3K/AKT factors. Such improvements have been concomitant with regulated neurotransmitter levels. We could conclude that citicoline may safely be supplemented to avoid both short- and long-term damages to the neuroendocrine disturbances, oxidative stress, inflammation, and apoptosis induced by head irradiation.

Temporal Leptin to Determine Cardiovascular and Metabolic Fate throughout the Life.

Leptin links peripheral adiposity and the central nervous system (CNS) to regulate cardiometabolic physiology. Within the CNS, leptin receptor-expressing cells are a counterpart to circulating leptin, and leptin receptor-mediated neural networks modulate the output of neuroendocrine and sympathetic nervous activity to balance cardiometabolic homeostasis. Therefore, disrupted CNS leptin signaling is directly implicated in the development of metabolic diseases, such as hypertension, obesity, and type 2 diabetes. Independently, maternal leptin also plays a central role in the development and growth of the infant during gestation. Accumulating evidence points to the dynamic maternal leptin environment as a predictor of cardiometabolic fate in their offspring as it is directly associated with infant metabolic parameters at birth. In postnatal life, the degree of serum leptin is representative of the level of body adiposity/weight, a driving factor for cardiometabolic alterations, and therefore, the levels of blood leptin through the CNS mechanism, in a large part, are a strong determinant for future cardiometabolic fate. The current review focuses on highlighting and discussing recent updates for temporal dissection of leptin-associated programing of future cardiometabolic fate throughout the entire life.