Neuroendocrinology (Neuroendocrinology )

Publisher: Karger

Description

ëNeuroendocrinologyí publishes papers reporting original research in basic and clinical neuroendocrinology. The journal explores the complex interactions between neuronal networks and endocrine glands (in some instances also immune cells) in both central and peripheral nervous systems. Original contributions cover all aspects of the field, from molecular and cellular neuroendocrinology, physiology, pharmacology, and the neuroanatomy of neuroendocrine systems to neuroendocrine correlates of coping behavior or clinical neuroendocrinology. Readers will also benefit from occasional, well-referenced reviews by noted experts which highlight especially active areas of current research.

  • Impact factor
    3.54
  • 5-year impact
    3.63
  • Cited half-life
    0.00
  • Immediacy index
    1.33
  • Eigenfactor
    0.01
  • Article influence
    1.01
  • Website
    Neuroendocrinology website
  • Other titles
    Neuroendocrinology (Online)
  • ISSN
    1423-0194
  • OCLC
    44647673
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Karger

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • On author or institutional server
    • Server must be non-commercial
    • Publisher's version/PDF cannot be used, unless Authors Choice fee is paid
    • Publisher copyright and source must be acknowledged
    • Must link to publisher version
    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The renin-angiotensin system (RAS) plays a major role in the control of blood pressure (BP) and water balance by coordinating brain, heart and kidney functions, connected with each other by hormonal and neural mechanisms through the autonomic nervous system (ANS). The RAS function may be monitored by the study of the enzymes (angiotensinases) involved in the metabolism of its active peptides. In order to study the relationship between the brain-heart-kidney axis in the control of BP and water balance, we analyzed the correlation of angiotensinase activities, assayed as arylamidase activities, between hypothalamus, left ventricle, renal cortex and renal medulla, collected from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), treated or not with L-NAME (N(G)-nitro-L-arginine methyl ester). This compound not only inhibits the formation of nitric oxide but also disrupts the normal function of the ANS activating the sympathetic nervous system (SNS) to increase BP. In addition, to assess the influence of the SNS, we studied the effect of its blockade by treatment of both strains with propranolol. The present results support the notion that the RAS function of the brain-heart-kidney axis, as reflected by the activities of angiotensinases, is reciprocally connected by afferent and efferent mechanisms between these locations, presumably through the ANS. These results reveal new aspects of neuroendocrine regulation possibly involving the ANS. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 10/2014;
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    ABSTRACT: Kisspeptin-Gpr54 signaling is critical for regulating the activity of gonadotropin releasing-hormone (GnRH) neurons in mammals. Previous studies have shown that the negative feedback mechanism is disrupted in global Gpr54-null mutants. The present investigation aimed to determine (1) if a lack of cyclical estrogen exposure of the GnRH neuronal network in the life-long hypogonadotropic Gpr54-null mice contributed to their failed negative feedback mechanism, and (2) the cellular location of disrupted kisspeptin-Gpr54 signaling. Plasma luteinizing hormone (LH) concentrations were determined in individual adult female mice when intact, following ovariectomy (OVX), and in response to an acute injection of 17β-estradiol (E2). Control mice exhibited a characteristic rise in LH after OVX that was suppressed by acute E2. Global Gpr54-null mice failed to exhibit any post-OVX increase in LH or response to E2. Adult female global Gpr54-null mice given a cyclical regimen of estradiol for three cycles prior to OVX also failed to exhibit any post-OVX increase in LH or response to E2. To address whether Gpr54 signaling at the GnRH neuron itself was necessary for the failed response to OVX in global Gpr54 null animals, adult female mice with a GnRH neuron-selective deletion of Gpr54 were examined. These mice also failed to exhibit any post-OVX increase in LH or response to E2. These experiments demonstrate defective negative feedback in global Gpr54-null mice that cannot be attributed to a lack of prior exposure of the GnRH neuronal network to cyclical estradiol. The absence of negative feedback in GnRH neuron-selective Gpr54-null mice demonstrates the necessity of direct kisspeptin signaling at the GnRH neuron for this mechanism to occur. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 10/2014;
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    ABSTRACT: Introduction: Recent data indicate that there is a link between depression and diabetes and that excess glucocorticoids may play an underlying role in the pathogenesis of both of these diseases. The aim of the present study was to determine whether there are any alterations in glucose, glycogen, glucose transporters, insulin, insulin receptors or corticosterone concentrations in the hippocampus and frontal cortex in a prenatal stress rat model of depression. Methods: Male rats whose mothers had been subjected to stress and control animals were subjected to the Porsolt test to verify the experimental model. Next, some of the rats were subjected to acute stress and/or were administered glucose. Glucose, glycogen, corticosterone, insulin, insulin receptors (IR), phospho-IR and glucose transporters (GLUT1, GLUT3 and GLUT4) concentrations were assayed. Results: Prenatally stressed rats exhibited glucose and glycogen concentrations in both investigated brain structures that exceeded those of the control animals. Prenatal stress also increased the levels of glucose transporters - GLUT1 in both tissues and GLUT4 in the frontal cortex. The changes in the prenatally stressed rats were more prominent in the animals that were subjected to stress or glucose loading in adulthood. Conclusion: In conclusion, the increase in carbohydrate brain concentrations evoked by prenatal stress may result from changes in the amounts of glucose transporters, especially GLUT1. Moreover, the obtained results support the hypothesis that stress during the perinatal period permanently increases the sensitivity of brain tissue to factors that act in adulthood. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 10/2014;
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    ABSTRACT: Background: This study was designed to evaluate the role of heat-shock protein 90 (HSP90) in tumor progression of murine islet cell tumors. Blockade of HSP90 has recently been proposed as a therapeutic target, but effects in models of islet cell tumors with AUY922, a newly developed HSP90-inhibitor, have not been examined. Material and Methods: The carcinoid cell line BON-1 and the HSP90 inhibitor AUY922 were used to determine effects on signalling and growth in vitro. In vivo transgenic RIP1-Tag2 mice, which develop islet cell neoplasms, were treated with vehicle or AUY922 (25 mg/kg/twice per week) from week 5 until death. The resected pancreata were evaluated macroscopically and microscopically by immunohistochemsistry. Quantitative real-time PCR was performed for HSP90 targets with RNA from islets, isolated from treated and untreated RIP1Tag2 mice. Results: HSP90 blockade impaired constitutive and growth factor-induced signalling in vitro. Moreover, HSP90 inhibition attenuated in vitro cell growth in a dose-dependent manner. In vivo, AUY922 significantly reduced tumor volume by 92% compared to untreated controls (p = 0.000) and median survival in the used transgenic mouse model was prolonged (110 vs. 119 days; p = 0.75). Quantitative real-time PCR for downstream target genes of HSP90 demonstrated significant down-regulation in the islet cell tumors of Rip1-Tag2 mice treated with AUY922, confirming our ability to achieve effective pharmacologic levels of AUY922 within the desired tissue site, in vivo. Conclusion: This is the first study to show that the HSP90 antagonist AUY922 may provide a new option for therapy of islet cell neoplasms. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 10/2014;
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    ABSTRACT: Purpose: To evaluate the effect of combined (68)Ga and (18)F-FDG PET/CT on treatment management for patients with pancreatic NET (PNET). Methods: Between January 2012 and April 2014, 49 consecutive patients with cytological and/or histological proven diagnosis of PNET underwent combined (68)Ga and (18)FDG PET/CT on the same day. Results: There were 21 males and 28 females with a median age of 59 years. (68)Ga imaging achieved disease detection in 48 out of 49 cases and (18)FDG PET/CT in 36 of 49 cases. These results corresponded to sensitivities of 98% for (68)Ga versus 73% for (18)FDG PET/CT. Patients with NET-G1/NET-G2 had positive (68)Ga and negative (18)FDG in 13 cases whereas both (68)Ga and (18)FDG PET/CT were positive in 27. Patients with NEC-G3 were both (68)Ga and (18)FDG PET/CT positive in 7 cases and only (18)FDG positive in one case. Another NEC G3 patient was only (68)Ga PET/CT positive. The median Ki67 was 7% for (68)Ga PET/CT positive tumors and 10% for tumors with both (68)Ga and (18)FDG PET/CT positive (p = 0.130). Half of patients with a prevalent uptake of 18FDG (n = 7) had a NEC G3 compared with the 12% of patients with a prevalent uptake of 68Ga (p = 0.012). There were no significant differences between patients with positive (68)Ga and those with positive (18)FDG as regards of treatment choice. Conclusions: The association of (18)FDG slightly increases sensitivity of (68)Ga PET/CT alone in the diagnosis of PNET. A combined dual tracer PET/CT does not influence the choice of treatment strategy. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 10/2014;
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    ABSTRACT: Exposure to stressors such as footshock leads to increased expression of multiple inflammatory factors, including the pro-inflammatory cytokine interleukin-1 (IL-1) in the brain. Studies have indicated that there are sex differences in stress reactivity, suggesting that the fluctuation of gonadal steroid levels across the estrous cycle may play a regulatory role in the stress-induced cytokine expression. The present studies were designed to investigate the role of estrogen (E2) and progesterone (Pg) in regulating the cytokine response within the paraventricular nucleus of the hypothalamus (PVN) through analysis of gene expression with real-time RT-PCR. Intact, cycling female rats showed a stress-induced increase in PVN IL-1 during the diestrus, proestrus, and estrus stages. During the metestrus stage, no change in IL-1 levels was seen following footshock; however ER-β levels did increase. Ovariectomy resulted in an increase in PVN IL-1, which was attenuated by treatment with estradiol benzoate (10 or 50 µg), indicating an E2- mediated anti-inflammatory effect. Ovarectomized rats treated with Pg (500 or 1,250 µg) showed no alteration in IL-1 levels, however Pg did up-regulate ER-β gene expression. The results from the current study implicate a potential mechanism through which high availability of endogenous Pg during the metestrus stage increases ER-β sensitivity, which in turn attenuates the PVN IL-1 response to stress. Thus, the interaction between gonadal steroid hormones and their central receptors throughout the estrous cycle may exert a powerful inhibitory influence on neuroimmune consequences of stress. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 10/2014;
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    ABSTRACT: Neuronal populations that synthesize kisspeptin (KP), neurokinin B (NKB) and substance P (SP) in the hypothalamic infundibular nucleus of humans are partly overlapping. These cells are important upstream regulators of gonadotropin-releasing hormone (GnRH) neurosecretion. Homologous neurons in laboratory animals are thought to modulate episodic GnRH secretion primarily via influencing KP receptors on the hypophysiotropic fiber projections of GnRH neurons. To explore the structural basis of this putative axo-axonal communication in humans, we analyzed the anatomical relationship of KP-immunoreactive (IR), NKB-IR and SP-IR axon plexuses with hypophysiotropic GnRH fiber projections. Immunohistochemical studies were carried out on histological samples from postmenopausal women. The neuropeptide-IR axons innervated densely the portal capillary network in the postinfundibular eminence. Subsets of the fibers formed descending tracts in the infundibular stalk, some reaching the neurohypophysis. KP-IR, NKB-IR and SP-IR plexuses intermingled, and established occasional contacts, with hypophysiotropic GnRH fibers in the postinfundibular eminence and through their lengthy course while descending within the infundibular stalk. Triple-immunofluorescent studies also revealed considerable overlap between the KP, NKB and SP signals in individual fibers, providing evidence that these peptidergic projections arise from neurons of the mediobasal hypothalamus. These neuroanatomical observations indicate that the hypophysiotropic projections of human GnRH neurons in the postinfundibular eminence and the descending GnRH tract coursing through the infundibular stalk to the neurohypophysis are exposed to neurotransmitters/neuropeptides released by dense KP-IR, NKB-IR and SP-IR fiber plexuses. Localization and characterization of axonal neuropeptide receptors will be required to clarify the putative autocrine and paracrine interactions in these anatomical regions. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 09/2014;
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    ABSTRACT: Introduction: The 'diurnal slope' of salivary cortisol has been used as a measure of stress and circadian function in a variety of reports with several detailing its association with cancer progression. The relationship of this slope, typically a negative value from high morning concentrations to low evening concentrations, to the underlying daily variation in total plasma cortisol throughout the 24-hour cycle, however, has never been reported. Methods: To examine the relationship between diurnal salivary cortisol slope and the underlying pattern of plasma cortisol in individuals with cancer, we examined a cohort of women with advanced breast cancer (n = 97) who had saliva and plasma collected during a modified 24-hour, constant posture protocol. Results: We found that steepness of the diurnal slope of salivary cortisol was correlated with the amplitude of plasma cortisol rhythm when the slope was calculated from samples taken at wake+30 min and 9PM (r = -0.29, p > 0.05). Other variants of salivary slope calculations were not significantly correlated with the amplitude of the plasma cortisol rhythm. Diurnal salivary cortisol slope steepness was not correlated with the time between habitual waking and the computed circadian peak of cortisol, but there was a correlation between diurnal slope steepness and the time between habitual waking and the time of the awakening spike of morning cortisol (r's<-0.23, p's<0.05). Conclusion: It therefore appears that in women with advanced breast cancer, diurnal salivary cortisol slope primarily represents aspects of the cortisol awakening response in relation to evening levels more than the circadian rhythm of total plasma cortisol. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 09/2014;
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    ABSTRACT: Background: Whether patients with small (<2 cm), sporadic non-functioning pancreatic endocrine tumors (NF-PETs) should directly undergo pancreatic surgery or should be followed longitudinally to detect growth and malignancy still has to be defined. Study Design: Based on the pertinent literature of the past decade, a Markov model was developed to investigate this issue. In the wait-and-see strategy arm, surgery was performed if the tumor attained a size ≥2 cm or surpassed 20% of the initial size. In a Monte Carlo probabilistic analysis, 100 hypothetical patients undergoing a wait-and-see strategy were compared to 100 patients directly undergoing surgery, with the aim of investigating the efficacy and cost-effectiveness of the two strategies. Results: During the post-diagnostic lifetime, 63 NF-PETs in the wait-and-see group showed significant growth and underwent surgery: 38 were Stage I, 10 were Stage II, 15 were stage III and none were Stage IV. In the base-case scenario, the mean life expectancy and quality-adjusted life expectancy were found to be superior after immediate surgery (26.1 years and 11.8 quality-adjusted life-years [QALYs]) than with the wait-and-see strategy (22.1 years and 8.3 QALYs) as the consequence of ageing during the wait-and-see follow-up which increased mortality due to surgery, when surgery was needed. The model was sensitive to starting age and length of follow-up; in particular, for patients >65 years of age, the two strategies provided similar results but the wait-and-see strategy was more cost-effective. Conclusions: The wait-and-see strategy for NF-PETs <2 cm represents a reasonable approach only in patients over 65 years of age; otherwise, immediate surgery is preferable. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 09/2014;
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    ABSTRACT: Background/Aims: Stress exacerbates neuron loss in many CNS injuries via the actions of adrenal glucocorticoid (GC) hormones. For some injuries, this GC-endangerment of neurons is accompanied by greater immune cell activation in the CNS, a surprising outcome given the potent immunosuppressive properties of GCs. Methods: To determine whether the effects of GCs on inflammation contribute to neuron death or result from it, we tested whether non-steroidal anti-inflammatory drugs could protect neurons from GCs during kainic acid excitotoxicity in adrenalectomized male rats. We next measured GC effects on (i) chemokine production (CCL2, CINC-1), (ii) signals that suppress immune activation (CX3CL1, CD22, CD200, and TGF-b), and (iii) NF-kB activity. Results: Concurrent treatment with minocycline but not indomethacin prevented GC-endangerment. GCs did not substantially affect CCL2, CINC-1, or baseline NF-kB activity, but they did suppress CX3CL1, CX3CR1, and CD22 expression in the hippocampus, factors that normally restrain inflammatory responses. Conclusions: These findings demonstrate that cellular inflammation is not necessarily suppressed by GCs in the injured hippocampus; instead, GCs may worsen hippocampal neuron death, at least in part, by increasing the neurotoxicity of CNS inflammation. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 09/2014;
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    ABSTRACT: In monogamous mammals, fathers play an important role in the development of the brain and typical behavior in offspring, but the exact nature of this process is not well understood. In particular, little research has addressed whether the presence or absence of paternal care alters levels of hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF), and basal levels of serum corticosterone (CORT) and adrenocorticotropin (ACTH). Here, we explore this concept using socially monogamous mandarin voles (Microtus mandarinus), a species in which fathers display high levels of paternal care toward their pups. Our immunohistochemical study shows that paternal deprivation (PD) significantly decreased levels of GR and BDNF protein in the CA1 and CA2/3 of the hippocampus. In the dental gyrus, decreases in GR and BDNF induced by PD were evident in females but not in males. Additionally, Elisa results show that PD significantly up-regulated levels of serum CORT and ACTH in females, but not males. These findings demonstrate that paternal deprivation alters HPA axis activity in a sex-specific way. The changes in stress hormones documented here may be associated with alteration in hippocampal BDNF and GR levels. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 08/2014;
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    ABSTRACT: A pivotal event in the onset of puberty in humans is the re-emergence of pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamic neurons. Pathways governing GnRH ontogeny and physiology have been discovered by studying animal models and humans with reproductive disorders. Recent human studies implicated the activation of the kisspeptin and its cognate receptor (KISS1- KISS1R), and the inactivation of the MKRN3 in the premature reactivation of the GnRH secretion, causing central precocious puberty (CPP). MKRN3, an imprinted gene located in the long arm of chromosome 15, encodes makorin ring finger protein 3 that is involved with ubiquitination and cell signaling. MKRN3 protein is derived only from RNA transcribed from the paternally inherited copy of the gene due to maternal imprinting. Currently, MKRN3 defects represent the most frequent known genetic cause of familial CPP. In this review, we explore the clinical, hormonal and genetic aspects of children with sporadic or familial CPP caused by mutations in the kisspeptin and MKRN3 systems, essential genetic factors for pubertal timing. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 08/2014;
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    ABSTRACT: Background/Aims: Kisspeptin is the major excitatory regulator of GnRH neurons and is responsible for basal GnRH/LH release and the GnRH/LH surge. Although it is widely assumed, based on mutations in kisspeptin and Kiss1R, that kisspeptin acts to sustain basal GnRH neuronal activity, there have been no studies to investigate whether endogenous basal kisspeptin tone plays a direct role in basal spontaneous GnRH neuronal excitability. It is also of interest to examine possible interactions between endogenous kisspeptin tone and other neuropeptides that have direct effects on GnRH neurons, such as NPY or CART, since the activity of all these neuropeptides changes during states of negative energy balance. Methods: Loose cell-attached and whole cell current-clamp patch recordings were made from GnRH-GFP neurons in hypothalamic slices from female and male rats. Results: Kisspeptin activated GnRH neurons in a concentration dependent manner with an EC50 of 3.32 ± 0.02 nM. Surprisingly, a kisspeptin antagonist, Peptide 347, suppressed spontaneous activity in GnRH neurons, demonstrating the essential nature of the endogenous kisspeptin tone. Furthermore, inhibition of endogenous kisspeptin tone blocked the direct activation of GnRH cells that occurs in response to antagonism of NPY Y5R or by CART. Conclusions: Our electrophysiology studies suggest that basal endogenous kisspeptin tone is not only essential for spontaneous GnRH neuronal firing, but it is also required for the net excitatory effects of other neuropeptides, such as CART or NPY antagonism, on GnRH neurons. Therefore, endogenous kisspeptin tone could serve as the linchpin in GnRH activation or inhibition. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 07/2014;
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    ABSTRACT: Background/Aims: Estrogens are important effectors of reproduction and are critical for upregulating female reproductive behavior or lordosis in females. In addition to the importance of transcriptional regulation of genes by 17β-estradiol-bound estrogen receptors (ERs), extra-nuclear signal transduction cascades such as protein kinase A (PKA) are also important in regulating female sexual receptivity. GPR30, also known as GPER1, a putative membrane ER (mER), is a G protein-coupled receptor that binds 17β-estradiol with an affinity that is similar to that possessed by the classical nuclear ER and activates both the PKA and extracellular regulated kinase signaling pathways. The high expression of GPR30 in the ventromedial hypothalamus, a region important for lordosis behavior, as well as kinase cascades activated by this receptor led us to hypothesize that GPR30 may regulate lordosis behavior in female rodents. Method: In this study, we investigated the ability of G-1, a selective agonist of GPR30, to regulate lordosis in the female mouse by administering this agent prior to progesterone in an estradiol-progesterone priming paradigm, prior to testing with stud males. Results: As expected, 17β-estradiol benzoate (EB), but not sesame oil, increased lordosis behavior in female mice. G-1 also increased lordosis behavior in female mice and decreased the number of rejective responses towards male mice, similar to the effect of EB. The selective GPR30 antagonist G-15 blocked these effects. Conclusion: This study demonstrates that activation of the membrane estrogen receptor GPR30 stimulates a social behavior in a rodent, in a manner similar to 17β-estradiol. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 07/2014;
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    ABSTRACT: Introduction: Cellular antioxidant signaling can be altered either by thyroid disturbances or by selenium status. Aims: To investigate whether or not dietary diphenyl diselenide could modify the expression of genes of antioxidant enzymes and endpoint markers of oxidative stress under hypothyroid condition. Methods: Female rats were rendered hypothyroid by continuous exposure to methimazole (MTZ; 20 mg/100 ml in the drinking water) for 3 months. Concomitantly, MTZ treated rats were either fed or not with a diet containing 5 ppm of diphenyl diselenide. mRNA levels of antioxidant enzymes and antioxidant/oxidant status were determined in cerebral cortex, hippocampus and striatum. Results: Hypothyroidism caused a marked up-regulation in mRNA expression of catalase (CAT), superoxide dismutase (SOD-1, SOD-3), glutathione peroxidase (GPx-1, GPx-4) and thioredoxin reductase (TrxR1) in brain structures. SOD-2 was increased in cortex and striatum, while TrxR2 increased in cerebral cortex. The increase in mRNA expression of antioxidant enzymes was positively correlated with the Nrf-2 transcription in cortex and hippocampus. Hypothyroidism caused oxidative stress, namely an increase in lipid peroxidation and ROS levels in hippocampus and striatum, and a decrease in non-protein thiols (NPSH) in cerebral cortex. Diphenyl diselenide was effective in reducing brain oxidative stress and normalizing most of changes observed in gene expression of antioxidant enzymes. Conclusion: The present work corroborates and extends that hypothyroidism disrupts the antioxidant enzyme gene expression and causes oxidative stress in the brain. Furthermore, diphenyl diselenide may be considered a promising molecule in counteracting these effects under hypothyroidism state. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 07/2014;
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    ABSTRACT: Aim: Accurate detection of recurrent disease and restaging are essential in the postoperative surveillance of many patients with pheochromocytomas (PHEOs) and paragangliomas (PGLs). In this study, the impact of positron emission tomography (PET) and PET/CT with (11)C-hydroxyephedrine (HED) was evaluated for the postoperative surveillance and diagnosis of recurrent disease and for functional monitoring of loco-regional andsystemic therapy. Methods: One hundred eleven HED-PET and PET/CT examinations performed in 48 patients after surgical intervention for PHEO/PGL were analyzed retrospectively. In a subgroup of 16 patients who underwent systemic and loco-regional therapies, the tracer uptake in tumors was also measured as the functional volume (FV),maximum standardized uptake value (SUVmax), mean SUV (SUVmean) and as the total catecholamine transporter tumor volume (TCTTV) calculated as TCTTV = FVxSUVmean. The PET imaging results were correlated to CT/MRI findings and biochemical and clinical follow-up data. Results: In the first postoperative examination, HED-PET was positive in 24/48 and negative in 24/48 patients with no false positive results, yielding 92.3% sensitivity and 100% specificity. For the 16 patients, there was a significant correlation between FV and SUVmax and SUVmax and TCTTV. TCTTV correlated significantly to plasma and urinary catecholamines. In 11/16 patients, SUVmax and TCTTV increased/decreased in parallel but not in the remaining five patients. Conclusion: HED-PET and PET/CT were found valuable in the postoperative follow-up in detecting recurrent and metastatic disease. In a subgroup of patients, functional monitoring of systemic and loco-regional therapies was feasible by assessing the changes of the TCTTV, and therefore warrants further prospective evaluation. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 07/2014;
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    ABSTRACT: Background/Aims: O6-Methyl-Guanine-Methyl-Transferase (MGMT) is an important enzyme of DNA repair. MGMT promoter methylation is detectable in a subset of pancreatic neuroendocrine neoplasms (pNEN). A subset of pNEN responds to the alkylating agent temozolomide (TMZ). We wanted to correlate MGMT promoter methylation with MGMT protein loss in pNEN, correlate the findings with clinico-pathological data and determine the role of MGMT to predict response to temozolomide chemotherapy. Methods: We analyzed a well characterized collective of 141 resected pNEN with median follow up of 83 months for MGMT protein expression and promoter methylation using methylation specific PCR (MSP). A second collective of 10 metastasized, pre-treated and progressive patients receiving TMZ was used to examine the predictive role of MGMT by determining protein expression and promoter methylation using primer extension based quantitative PCR. Results: In both collectives there was no correlation between MGMT protein expression and promoter methylation. Loss of MGMT protein was associated with an adverse outcome, this prognostic value, however, was not independent from grade and stage in multivariate analysis. Promoter hypermethylation was significantly associated with response to TMZ. Conclusion: Loss of MGMT protein expression is associated with adverse outcome in a surgical series of pNET. MGMT promoter methylation could be a predictive marker for TMZ chemotherapy in pNEN, but further, favourably prospective studies will be needed to confirm this result and before this observation can influence clinical routine. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 07/2014;