scholarly journals New Perspectives for Anatomical and Molecular Studies of Kisspeptin Neurons in the Aging Human Brain

2019 ◽  
Vol 109 (3) ◽  
pp. 230-241 ◽  
Author(s):  
Erik Hrabovszky ◽  
Szabolcs Takács ◽  
Balázs Göcz ◽  
Katalin Skrapits
Keyword(s):  
Arcuate Nucleus ◽  
Anatomical Site ◽  
Neuronal System ◽  
Hormone Signaling ◽  
Neurokinin B ◽  
Molecular Approaches ◽  
Endocrine Organs ◽  
Aging Men ◽  
Gnrh Neurons

The human infundibular nucleus (corresponding to the rodent arcuate nucleus) serves as an important integration center for neuronal signals and hormones released by peripheral endocrine organs. Kisspeptin (KP)-producing neurons of this anatomical site, many of which also synthesize neurokinin B (NKB), are critically involved in sex hormone signaling to gonadotropin-releasing hormone (GnRH) neurons. In recent years, the basic topography, morphology, neuropeptide content, and connectivity of human KP neurons have been investigated with in situ hybridization and immunohistochemistry on postmortem tissues. These studies revealed that human KP neurons differ neurochemically from their rodent counterparts and show robust aging-related plasticity. Earlier immunohistochemical experiments also provided evidence for temporal changes in the hypothalamus of aging men whose NKB and KP neurons undergo hypertrophy, increase in number, exhibit increased neuropeptide mRNA expression and immunoreactivity and give rise to higher numbers of immunoreactive fibers and afferent contacts onto GnRH neurons. Increasing percentages of KP-expressing NKB perikarya, NKB axons, and NKB inputs to GnRH neurons raise the intriguing possibility that a significant subset of NKB neurons begins to cosynthesize KP as aging advances. Although use of postmortem tissues is technically challenging, recently available single-cell anatomical and molecular approaches discussed in this review provide promising new tools to investigate the aging-related anatomical and functional plasticity of the human KP neuronal system.

scholarly journals Estrogen and Estrogen Receptor-β (ERβ)-Selective Ligands Induce Galanin Expression within Gonadotropin Hormone-Releasing Hormone-Immunoreactive Neurons in the Female Rat Brain

Endocrinology ◽  
2005 ◽  
Vol 146 (6) ◽  
pp. 2760-2765 ◽  
Author(s):  
Istvan Merchenthaler ◽  
Gloria E. Hoffman ◽  
Malcolm V. Lane
Keyword(s):  
Ovariectomized Rats ◽  
Female Rat ◽  
Dependent Manner ◽  
Neuronal System ◽  
Selective Ligands ◽  
Gnrh Neurons ◽  
17Β Estradiol ◽  
Selective Agonists ◽  
The Many

Abstract Among the many factors that integrate the activity of the GnRH neuronal system, estrogens play the most important role. In females, estrogen, in addition to the negative feedback, also exhibits a positive feedback influence upon the activity and output of GnRH neurons to generate the preovulatory LH surge and ovulation. Until recently, the belief has been that the GnRH neurons do not contain estrogen receptors (ERs) and that the action of estrogen upon GnRH neurons is indirect involving several, estrogen-sensitive neurotransmitter and neuromodulator systems that trans-synaptically regulate the activity of the GnRH neurons. Based on our recent findings that GnRH neurons of the female rat coexpress galanin, that galanin is a potent GnRH-releasing peptide, and that ERβ is present in GnRH neurons, we have evaluated the effect of 17β-estradiol and two ERβ-selective agonists (WAY-200070, WAY-166818) on the expression of galanin within GnRH neurons. By combining immunocytochemistry for GnRH and in situ hybridization histochemistry for galanin, we demonstrate that 17β-estradiol (20 μg/kg, sc) stimulates galanin expression within GnRH-immunoreactive neurons in a time-dependent manner. A significant increase was observed 2 h after its administration to ovariectomized rats. However, a more robust expression required 3-d treatment regimen. Treatment with the β-selective ligands resulted in similar observations, although no statistical analysis is available for the 2 hr survival. These observations strongly suggest that estrogen and the ERβ-selective ligands stimulate galanin expression within GnRH neurons via ERβ, although an indirect mechanism via interneurons still cannot be ruled out.

scholarly journals Evidence That Dynorphin Acts Upon KNDy and GnRH Neurons During GnRH Pulse Termination in the Ewe

Endocrinology ◽  
2018 ◽  
Vol 159 (9) ◽  
pp. 3187-3199 ◽  
Author(s):  
Peyton W Weems ◽  
Lique M Coolen ◽  
Stanley M Hileman ◽  
Steven Hardy ◽  
Rick B McCosh ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Third Ventricle ◽  
Pulse Generation ◽  
G Protein Coupled Receptors ◽  
Neurokinin B ◽  
Gnrh Secretion ◽  
Pulsatile Gnrh ◽  
Gnrh Neurons ◽  
Kndy Neurons ◽  
G Protein Coupled

Abstract A subpopulation of neurons located within the arcuate nucleus, colocalizing kisspeptin, neurokinin B, and dynorphin (Dyn; termed KNDy neurons), represents key mediators of pulsatile GnRH secretion. The KNDy model of GnRH pulse generation proposes that Dyn terminates each pulse. However, it is unknown where and when during a pulse that Dyn is released to inhibit GnRH secretion. Dyn acts via the κ opioid receptor (KOR), and KOR is present in KNDy and GnRH neurons in sheep. KOR, similar to other G protein–coupled receptors, are internalized after exposure to ligand, and thus internalization can be used as a marker of endogenous Dyn release. Thus, we hypothesized that KOR will be internalized at pulse termination in both KNDy and GnRH neurons. To test this hypothesis, GnRH pulses were induced in gonad-intact anestrous ewes by injection of neurokinin B (NKB) into the third ventricle and animals were euthanized at times of either pulse onset or termination. NKB injections produced increased internalization of KOR within KNDy neurons during both pulse onset and termination. In contrast, KOR internalization into GnRH neurons was seen only during pulse termination, and only in GnRH neurons within the mediobasal hypothalamus (MBH). Overall, our results indicate that Dyn is released onto KNDy cells at the time of pulse onset, and continues to be released during the duration of the pulse. In contrast, Dyn is released onto MBH GnRH neurons only at pulse termination and thus actions of Dyn upon KNDy and GnRH cell bodies may be critical for pulse termination.

scholarly journals Projections of Arcuate Nucleus and Rostral Periventricular Kisspeptin Neurons in the Adult Female Mouse Brain

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2387-2399 ◽  
Author(s):  
Shel-Hwa Yeo ◽  
Allan E. Herbison
Keyword(s):  
Mouse Brain ◽  
Female Mouse ◽  
Arcuate Nucleus ◽  
Third Ventricle ◽  
Retrograde Tracing ◽  
Neuron Activity ◽  
Neuronal System ◽  
Gnrh Neuron ◽  
Gnrh Neurons ◽  
Tracing Techniques

The important role of kisspeptin neurons in the regulation of GnRH neuron activity is now well accepted. However, the ways in which kisspeptin neurons located in the arcuate nucleus (ARN) and rostral periventricular area of the third ventricle (RP3V) control GnRH neurons are poorly understood. The present study used anterograde and retrograde tracing techniques to establish the neuronal projection patterns of kisspeptin cell populations in the female mouse brain. Anterograde tracing studies revealed that kisspeptin neurons in the ARN innervated a wide number of hypothalamic and associated limbic region nuclei, whereas RP3V kisspeptin neurons projected to a smaller number of mostly medially located hypothalamic nuclei. Retrograde tracing confirmed a major projection of RP3V kisspeptin neurons to the ARN and showed that kisspeptin neurons located in the rostral half of the ARN projected to the rostral preoptic area. Peripheral administration of Fluorogold was found to label the majority of GnRH neurons but no kisspeptin neurons. Together, these studies highlight the complexity of the brain kisspeptin neuronal system and indicate that both ARN and RP3V kisspeptin neurons participate in a variety of limbic functions. In relation to the GnRH neuronal network, these investigations demonstrate that, alongside the RP3V kisspeptin cells, rostral ARN kisspeptin neurons may also project to GnRH neuron cell bodies. However, no kisspeptin neurons innervate GnRH nerve terminals in the external layer of the median eminence. These studies provide a neuroanatomical framework for the further elucidation of the functions of the ARN and RP3V kisspeptin neuron populations.

scholarly journals Development, Sex Steroid Regulation, and Phenotypic Characterization of RFamide-Related Peptide (Rfrp) Gene Expression and RFamide Receptors in the Mouse Hypothalamus

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1827-1840 ◽  
Author(s):  
Matthew C. Poling ◽  
Joshua Kim ◽  
Sangeeta Dhamija ◽  
Alexander S. Kauffman
Keyword(s):  
In Situ Hybridization ◽  
Estrogen Receptor Α ◽  
Cell Number ◽  
Phenotypic Characterization ◽  
Related Peptide ◽  
Adult Mice ◽  
Gnrh Neurons ◽  
Double Label ◽  
Hormonal Milieu

Arginine-phenylalanine-amide (RFamide)-related peptide 3 (RFRP-3, encoded by the Rfrp gene) is the mammalian ortholog of gonadotropin-inhibiting hormone and can inhibit GnRH neuronal activity and LH release. However, the development and regulation of the RFRP-3 system in both sexes is poorly understood. Using in situ hybridization, we examined changes in Rfrp-expressing neurons in mice of both sexes during development and under different adulthood hormonal milieus. We found no sex differences in Rfrp expression or cell number in adult mice. Interestingly, we identified two interspersed subpopulations of Rfrp cells (high Rfrp-expressing, HE; low Rfrp-expressing, LE), which have unique developmental and steroidal regulation characteristics. The number of LE cells robustly decreases during postnatal development, whereas HE cell number increases significantly before puberty. Using Bax knockout mice, we determined that the dramatic developmental decrease in LE Rfrp cells is not due primarily to BAX-dependent apoptosis. In adults, we found that estradiol and testosterone moderately repress Rfrp expression in both HE and LE cells, whereas the nonaromatizable androgen dihydrotestosterone has no effect. Using double-label in situ hybridization, we determined that approximately 25% of Rfrp neurons coexpress estrogen receptor-α in each sex, whereas Rfrp cells do not readily express androgen receptor in either sex, regardless of hormonal milieu. Lastly, when we looked at RFRP-3 receptors, we detected some coexpression of Gpr147 but no coexpression of Gpr74 in GnRH neurons of both intact and gonadectomized males and females. Thus, RFRP-3 may exert its effects on reproduction either directly, via Gpr147 in a subset of GnRH neurons, and/or indirectly, via upstream regulators of GnRH.

Localization and genotyping of canine papillomavirus in canine inverted papillomas

2021 ◽  
pp. 104063872110357
Author(s):  
Margherita Orlandi ◽  
Maurizio Mazzei ◽  
Marta Vascellari ◽  
Erica Melchiotti ◽  
Claudia Zanardello ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Inclusion Bodies ◽  
Animal Species ◽  
Viral Etiology ◽  
Molecular Approaches ◽  
Dna And Rna ◽  
Promising Tool ◽  
First Choice ◽  
Inverted Papillomas

Numerous canine papillomaviruses (CPVs) have been identified (CPV1–23). CPV1, 2, and 6 have been associated with inverted papillomas (IPs). We retrieved 19 IPs from 3 histopathology archives, and evaluated and scored koilocytes, inclusion bodies, giant keratohyalin granules, cytoplasmic pallor, ballooning degeneration, and parakeratosis. IHC targeting major capsid proteins of PV was performed, and CPV genotyping was achieved by PCR testing. Tissue localization of CPV DNA and RNA was studied by chromogenic and RNAscope in situ hybridization (DNA-CISH, RNA-ISH, respectively). IPs were localized to the limbs (50%), trunk (30%), and head (20%), mainly as single nodules (16 of 19). In 15 of 19 cases, immunopositivity was detected within the nuclei in corneal and subcorneal epidermal layers. PCR revealed CPV1 in 11 IPs and CPV2 DNA in 3 IPs. Overall, 14 of 17 cases were positive by both DNA-CISH and RNA-ISH, in accord with PCR results. A histologic score >5 was always obtained in cases in which the viral etiology was demonstrated by IHC, DNA-CISH, and RNA-ISH. IHC and molecular approaches were useful to ascertain the viral etiology of IPs. Although IHC is the first choice for diagnostic purposes, ISH testing allows identification of PV type and the infection phase. RNA-ISH seems a promising tool to deepen our understanding of the pathogenesis of different PV types in animal species.

Influence of photoperiod and gonadal status on food intake, adiposity, and gene expression of hypothalamic appetite regulators in a seasonal mammal

2007 ◽  
Vol 292 (1) ◽  
pp. R242-R252 ◽  
Author(s):  
Chantacha Anukulkitch ◽  
Alexandra Rao ◽  
Frank R. Dunshea ◽  
Dominique Blache ◽  
Gerald A. Lincoln ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Reproductive Axis ◽  
Pomc Gene ◽  
Gonadal Status ◽  
Long Photoperiod ◽  
Refractory Phase

We studied the effects of photoperiod on metabolic profiles, adiposity, and gene expression of hypothalamic appetite-regulating peptides in gonad-intact and castrated Soay rams. Groups of five to six animals were studied 6, 18, or 30 wk after switching from long photoperiod (LP: 16 h of light) to short photoperiod (SP: 8 h of light). Reproductive and metabolic indexes were measured in blood plasma. Expression of neuropeptide Y (NPY), proopiomelanocortin (POMC), and leptin receptor (ObRb) in the arcuate nucleus was measured using in situ hybridization. Testosterone levels of intact animals were low under LP, increased to a peak at 16 wk under SP, and then declined. Voluntary food intake (VFI) was high under LP in both intact and castrated animals, decreased to a nadir at 12–16 wk under SP, and then recovered, but only in intact rams as the reproductive axis became photorefractory to SP. NPY gene expression varied positively and POMC expression varied negatively with the cycle in VFI, with differences between intact and castrate rams in the refractory phase. ObRb expression decreased under SP, unrelated to changes in VFI. Visceral fat weight also varied between the intact and castrated animals across the cycle. We conclude that 1) photoperiodic changes in VFI reflect changes in NPY and POMC gene expression, 2) changes in ObRb gene expression are not necessarily determinants of changes in VFI, 3) gonadal status affects the pattern of VFI that changes with photoperiod, and 4) in the absence of gonadal factors, animals can eat less but gain adiposity.

scholarly journals Colonisation of basal cell carcinoma and actinic keratosis by malignant melanoma in situ in a patient with xeroderma pigmentosum variant

2012 ◽  
Vol 2 (2) ◽  
pp. 47 ◽  
Author(s):  
Louise J. Smith ◽  
Ehab A. Husain
Keyword(s):  
Malignant Melanoma ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Actinic Keratosis ◽  
Xeroderma Pigmentosum ◽  
Clinical Impression ◽  
Anatomical Site ◽  
History Of

Although malignant melanoma (MM) and both basal cell carcinoma (BCC) and actinic keratosis (AK) are sun-induced lesions, the coexistence of these entities at the same anatomical site (collision tumour) is exceedingly rare. We report the case of a 54-year-old woman with a known history of xeroderma pigmentosum variant (XPV) who presented with 2 separate skin lesions over the middle and upper right forearm, respectively. The clinical impression was that of BCCs or squamous cell lesions. On histological examination, both specimens showed features of melanoma <em>in situ </em>(MIS). In the first lesion, MIS merged with and colonised a superficial and focally invasive BCC. In the second lesion, MIS merged with an AK. No separate invasive nests of malignant melanoma were seen in either specimen. The atypical melanocytes were highlighted by Melan-A and HMB-45 immunostaining, whereas the epithelial cells in both the BCC and AK stained with the pancytokeratin MNF-116. The patient had a previous history of multiple MMs and non-melanomatous skin cancers and finally developed widespread metastatic malignant melanoma, which proved fatal. The rare and interesting phenomenon of collision tumours may pose diagnostic difficulties. To our knowledge, this is the first reported simultaneous presentation of cytologically malignant collision tumours in a patient with XPV.

Sign in / Sign up

Export Citation Format

Share Document