scholarly journals Expression of type one cannabinoid receptor in different subpopulation of kisspeptin neurons and kisspeptin afferents to GnRH neurons in female mice

2021 ◽  
Author(s):  
Tamás Wilheim ◽  
Krisztina Nagy ◽  
Mahendravarman Mohanraj ◽  
Kamil Ziarniak ◽  
Masahiko Watanabe ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Third Ventricle ◽  
Glutamate Transporter ◽  
Neuroendocrine Cells ◽  
Receptor Protein ◽  
Specific Expression ◽  
Female Mice ◽  
Gnrh Neurons ◽  
Periventricular Area ◽  
Cycle Dependent

AbstractThe endocannabinoids have been shown to target the afferents of hypothalamic neurons via cannabinoid 1 receptor (CB1) and thereby to influence their excitability at various physiological and/or pathological processes. Kisspeptin (KP) neurons form afferents of multiple neuroendocrine cells and influence their activity via signaling through a variation of co-expressed classical neurotransmitters and neuropeptides. The differential potency of endocannabinoids to influence the release of classical transmitters or neuropeptides, and the ovarian cycle-dependent functioning of the endocannabinoid signaling in the gonadotropin-releasing hormone (GnRH) neurons initiated us to study whether (a) the different subpopulations of KP neurons express CB1 mRNAs, (b) the expression is influenced by estrogen, and (c) CB1-immunoreactivity is present in the KP afferents to GnRH neurons. The aim of the study was to investigate the site- and cell-specific expression of CB1 in female mice using multiple labeling in situ hybridization and immunofluorescent histochemical techniques. The results support that CB1 mRNAs are expressed by both the GABAergic and glutamatergic subpopulations of KP neurons, the receptor protein is detectable in two-thirds of the KP afferents to GnRH neurons, and the expression of CB1 mRNA shows an estrogen-dependency. The applied estrogen-treatment, known to induce proestrus, reduced the level of CB1 transcripts in the rostral periventricular area of the third ventricle and arcuate nucleus, and differently influenced its co-localization with vesicular GABA transporter or vesicular glutamate transporter-2 in KP neurons. This indicates a gonadal cycle-dependent role of endocannabinoid signaling in the neuronal circuits involving KP neurons.

scholarly journals Lactational Anovulation in Mice Results From a Selective Loss of Kisspeptin Input to GnRH Neurons

Endocrinology ◽  
2014 ◽  
Vol 155 (1) ◽  
pp. 193-203 ◽  
Author(s):  
X. Liu ◽  
R.S.E. Brown ◽  
A.E. Herbison ◽  
D.R. Grattan
Keyword(s):  
Brain Slice ◽  
Third Ventricle ◽  
Late Pregnancy ◽  
Mrna Levels ◽  
Fiber Density ◽  
Selective Loss ◽  
Fold Reduction ◽  
Gnrh Neurons ◽  
Periventricular Area ◽  
Brain Slice Preparation

In mammals, lactation is associated with a period of infertility characterized by the loss of pulsatile secretion of GnRH and cessation of ovulatory cycles. Despite the importance of lactational infertility in determining overall fecundity of a species, the mechanisms by which the suckling stimulus suppresses GnRH secretion remain unclear. Because kisspeptin neurons are critical for fertility, the aim of this study was to test the hypothesis that reduced kisspeptin expression might mediate the lactation-induced suppression of fertility, using mouse models. In the rostral periventricular area of the third ventricle (RP3V), a progressive decrease in RP3V Kiss1 mRNA levels was observed during pregnancy culminating in a 10-fold reduction during lactation compared with diestrous controls. This was associated with approximately 60% reduction in the numbers of kisspeptin-immunoreactive neurons in the RP3V detected during lactation. Similarly, in the arcuate nucleus there was also a significant decrease in Kiss1 mRNA levels during late pregnancy and midlactation, and a notable decrease in kisspeptin fiber density during lactation. The functional characteristics of the RP3V kisspeptin input to GnRH neurons were assessed using electrophysiological approaches in an acute brain slice preparation. Although endogenous RP3V kisspeptin neurons were found to activate GnRH neurons in diestrous mice, this was never observed during lactation. This did not result from an absence of kisspeptin receptors because GnRH neurons responded normally to 100 nM exogenous kisspeptin during lactation. The kisspeptin deficit in lactating mice was selective, because GnRH neurons responded normally to RP3V gamma aminobutryic acid inputs during lactation. These data demonstrate that a selective loss of RP3V kisspeptin inputs to GnRH neurons during lactation is the likely mechanism causing lactational anovulation in the mouse.

scholarly journals Genetic Deletion of Esr1 in the Mouse Preoptic Area Disrupts the LH Surge and Estrous Cyclicity

Endocrinology ◽  
2019 ◽  
Vol 160 (8) ◽  
pp. 1821-1829 ◽  
Author(s):  
Robert Porteous ◽  
Allan E Herbison
Keyword(s):  
Estrogen Receptor ◽  
Third Ventricle ◽  
Estrogen Receptor Α ◽  
Adeno Associated Virus ◽  
Estrous Cycles ◽  
Lh Surge ◽  
Periventricular Nucleus ◽  
Gnrh Neurons ◽  
Estrous Cyclicity ◽  
Periventricular Area

Abstract Estrogen receptor α (ESR1) is critical for the generation of the preovulatory LH surge. Experiments in rodents have indicated a role for neurons located in the anteroventral periventricular area and preoptic periventricular nucleus [termed the rostral periventricular area of the third ventricle (RP3V)] in surge generation. In the current study, we aimed to examine whether ESR1 expressed by RP3V neurons was necessary for the LH surge. The estrous cycles of mice with estrogen receptor α (Esr1) exon 3 flanked by LoxP sites (Esr1 flox) and controls were monitored before and after bilateral stereotactic injection of adeno-associated virus encoding Cre recombinase into the RP3V. This resulted in 84% and 72% decreases in ESR1-immunoreactive cell numbers in the anteroventral periventricular area and preoptic periventricular nucleus, respectively, with no changes in the arcuate nucleus. Beginning three weeks after the adeno-associated virus injection, Esr1 flox mice began to show a loss of estrous cyclicity going, primarily, into constant estrus. Wild-type mice and Esr1 flox mice with injections outside the RP3V or unilateral ablations of ESR1 continued to exhibit normal estrous cycles. Mice were then gonadectomized and given an estradiol replacement regimen to generate the LH surge. This resulted in an absence of cFOS expression in GnRH neurons (1 ± 1% vs 28 ± 4% of GnRH neurons; P < 0.01) and markedly reduced LH surge levels (2.5 ± 0.6 vs 9.1 ± 1.0 ng/mL; P < 0.01) in Esr1 flox mice compared with controls. These results demonstrate that neurons expressing ESR1 within the RP3V are critical for the generation of the LH surge and estrous cyclicity in the mouse.

scholarly journals Sensory Detection by the Vomeronasal Organ Modulates Experience-Dependent Social Behaviors in Female Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Anne-Charlotte Trouillet ◽  
Chantal Moussu ◽  
Kevin Poissenot ◽  
Matthieu Keller ◽  
Lutz Birnbaumer ◽  
...  
Keyword(s):  
Social Behavior ◽  
Third Ventricle ◽  
Vomeronasal Organ ◽  
Social Behaviors ◽  
Sensory Function ◽  
Sexual Receptivity ◽  
Vomeronasal System ◽  
Female Mice ◽  
Pup Retrieval ◽  
Periventricular Area

In mice, social behaviors are largely controlled by the olfactory system. Pheromone detection induces naïve virgin females to retrieve isolated pups to the nest and to be sexually receptive to males, but social experience increases the performance of both types of innate behaviors. Whether animals are intrinsically sensitive to the smell of conspecifics, or the detection of olfactory cues modulates experience for the display of social responses is currently unclear. Here, we employed mice with an olfactory-specific deletion of the G protein Gαi2, which partially eliminates sensory function in the vomeronasal organ (VNO), to show that social behavior in female mice results from interactions between intrinsic mechanisms in the vomeronasal system and experience-dependent plasticity. In pup- and sexually-naïve females, Gαi2 deletion elicited a reduction in pup retrieval behavior, but not in sexual receptivity. By contrast, experienced animals showed normal maternal behavior, but the experience-dependent increase in sexual receptivity was incomplete. Further, lower receptivity was accompanied by reduced neuronal activity in the anterior accessory olfactory bulb and the rostral periventricular area of the third ventricle. Therefore, neural mechanisms utilize intrinsic sensitivity in the mouse vomeronasal system and enable plasticity to display consistent social behavior.

scholarly journals Activation of Glutamate Transporter-1 (GLT-1) Confers Sex-Dependent Neuroprotection in Brain Ischemia

2021 ◽  
Vol 11 (1) ◽  
pp. 76
Author(s):  
Flavia A. Tejeda-Bayron ◽  
David E. Rivera-Aponte ◽  
Christian J. Malpica-Nieves ◽  
Gerónimo Maldonado-Martínez ◽  
Héctor M. Maldonado ◽  
...  
Keyword(s):  
Infarct Size ◽  
Glutamate Transporter ◽  
Triphenyltetrazolium Chloride ◽  
Stroke Outcomes ◽  
Female Mice ◽  
Protein Levels ◽  
Translational Activator ◽  
Glutamate Transporter 1 ◽  
Sensorimotor Performance

Stroke is one of the leading causes of long-term disability. During ischemic stroke, glutamate is released, reuptake processes are impaired, and glutamate promotes excitotoxic neuronal death. Astrocytic glutamate transporter 1 (GLT-1) is the major transporter responsible for removing excess glutamate from the extracellular space. A translational activator of GLT-1, LDN/OSU 0212320 (LDN) has been previously developed with beneficial outcomes in epileptic animal models but has never been tested as a potential therapeutic for ischemic strokes. The present study evaluated the effects of LDN on stroke-associated brain injury. Male and female mice received LDN or vehicle 24 h before or 2 h after focal ischemia was induced in the sensorimotor cortex. Sensorimotor performance was determined using the Rung Ladder Walk and infarct area was assessed using triphenyltetrazolium chloride staining. Males treated with LDN exhibited upregulated GLT-1 protein levels, significantly smaller infarct size, and displayed better sensorimotor performance in comparison to those treated with vehicle only. In contrast, there was no upregulation of GLT-1 protein levels and no difference in infarct size or sensorimotor performance between vehicle- and LDN-treated females. Taken together, our results indicate that the GLT-1 translational activator LDN improved stroke outcomes in young adult male, but not female mice.

scholarly journals Expression of beta-nerve growth factor and its receptor in rat seminiferous epithelium: specific function at the onset of meiosis.

1992 ◽  
Vol 117 (3) ◽  
pp. 629-641 ◽  
Author(s):  
M Parvinen ◽  
M Pelto-Huikko ◽  
O Söder ◽  
R Schultz ◽  
A Kaipia ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Sertoli Cells ◽  
Seminiferous Epithelium ◽  
Receptor Protein ◽  
Tyrosine Kinase Receptor ◽  
Specific Expression ◽  
Nerve Growth ◽  
Ngf Receptor

beta-Nerve growth factor (NGF) is expressed in spermatogenic cells and has testosterone-downregulated low-affinity receptors on Sertoli cells suggesting a paracrine role in the regulation of spermatogenesis. An analysis of the stage-specific expression of NGF and its low affinity receptor during the cycle of the seminiferous epithelium in the rat revealed NGF mRNA and protein at all stages of the cycle. Tyrosine kinase receptor (trk) mRNA encoding an essential component of the high-affinity NGF receptor was also present at all stages. In contrast, expression of low affinity NGF receptor mRNA was only found in stages VIIcd and VIII of the cycle, the sites of onset of meiosis. The low-affinity NGF receptor protein was present in the plasma membrane of the apical Sertoli cell processes as well as in the basal plasma membrane of these cells at stages VIIcd to XI. NGF was shown to stimulate in vitro DNA synthesis of seminiferous tubule segments with preleptotene spermatocytes at the onset of meiosis while other segments remained nonresponsive. We conclude that NGF is a meiotic growth factor that acts through Sertoli cells.

scholarly journals Joint changes in RNA, RNA polymerase II, and promoter activity through the cell cycle identify non-coding RNAs involved in proliferation

2021 ◽  
Author(s):  
Siv Anita Hegre ◽  
Helle Samdal ◽  
Antonin Klima ◽  
Endre B. Stovner ◽  
Kristin G. Nørsett ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Promoter Activity ◽  
Cycle Phase ◽  
Specific Expression ◽  
Chip Sequencing ◽  
Non Coding Rnas ◽  
Cycle Dependent ◽  
Rna Levels

AbstractProper regulation of the cell cycle is necessary for normal growth and development of all organisms. Conversely, altered cell cycle regulation often underlies proliferative diseases such as cancer. Long non-coding RNAs (lncRNAs) are recognized as important regulators of gene expression and are often found dysregulated in diseases, including cancers. However, identifying lncRNAs with cell cycle functions is challenging due to their often low and cell-type specific expression. We present a highly effective method that analyses changes in promoter activity, transcription, and RNA levels for identifying genes enriched for cell cycle functions. Specifically, by combining RNA sequencing with ChIP sequencing through the cell cycle of synchronized human keratinocytes, we identified 1009 genes with cell cycle-dependent expression and correlated changes in RNA polymerase II occupancy or promoter activity as measured by histone 3 lysine 4 trimethylation (H3K4me3). These genes were highly enriched for genes with known cell cycle functions and included 59 lncRNAs. We selected four of these lncRNAs – AC005682.5, RP11-132A1.4, ZFAS1, and EPB41L4A-AS1 – for further experimental validation and found that knockdown of each of the four lncRNAs affected cell cycle phase distributions and reduced proliferation in multiple cell lines. These results show that many genes with cell cycle functions have concomitant cell-cycle dependent changes in promoter activity, transcription, and RNA levels and support that our multi-omics method is well suited for identifying lncRNAs involved in the cell cycle.

scholarly journals Integrative Transcriptomics and Proteomics Analyses to Reveal the Developmental Regulation of Metorchis orientalis: A Neglected Trematode With Potential Carcinogenic Implications

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun-Feng Gao ◽  
Qing-Bo Lv ◽  
Rui-Feng Mao ◽  
Yun-Yi Sun ◽  
Ying-Yu Chen ◽  
...  
Keyword(s):  
Nucleocytoplasmic Transport ◽  
Protein Quantification ◽  
Differentially Expressed ◽  
Receptor Protein ◽  
Proteomics Data ◽  
Potential Threat ◽  
Serine Threonine Kinase ◽  
Specific Expression ◽  
Threonine Kinase ◽  
Gene And Protein Expression

Metorchis orientalis is a neglected zoonotic parasite of the gallbladder and bile duct of poultry, mammals, and humans. It has been widely reported in Asian, including China, Japanese, and Korea, where it is a potential threat to public health. Despite its significance as an animal and human pathogen, there are few published transcriptomic and proteomics data available. Transcriptome Illumina RNA sequencing and label-free protein quantification were performed to compare the gene and protein expression of adult and metacercariae-stage M. orientalis, resulting in 100,234 unigenes and 3,530 proteins. Of these, 13,823 differentially expressed genes and 1,445 differentially expressed proteins were identified in adult versus metacercariae. In total, 570 genes were differentially expressed consistent with the mRNA and protein level in the adult versus metacercariae stage. Differential gene transcription analyses revealed 34,228 genes to be expressed in both stages, whereas 66,006 genes showed stage-specific expression. Compared with adults, the metacercariae stage was highly transcriptional. GO and KEGG analyses based on transcriptome and proteome revealed numerous up-regulated genes in adult M. orientalis related to microtubule-based processes, microtubule motor activity, and nucleocytoplasmic transport. The up-regulated genes in metacercariae M. orientalis were mainly related to transmembrane receptor protein serine/threonine kinase activity, transmembrane receptor protein serine/threonine kinase signaling pathway. Transcriptome and proteome comparative analyses showed numerous up-regulated genes in adult stage were mainly enriched in actin filament capping, spectrin, and glucose metabolic process, while up-regulated genes in metacercariae stage were mainly related to cilium assembly, cilium movement, and motile cilium. These results highlight changes in protein and gene functions during the development of metacercariae into adults, and provided evidence for the mechanisms involved in morphological and metabolic changes at both the protein and gene levels. Interestingly, many genes had been proved associated with liver fibrosis and carcinogenic factors were identified highly expressed in adult M. orientalis, which suggests that M. orientalis is a neglected trematode with potential carcinogenic implications. These data provide attractive targets for the development of therapeutic or diagnostic interventions for controlling M. orientalis.

scholarly journals Pup removal suppresses estrogen-induced surges of LH secretion and activation of GnRH neurons in lactating rats

2006 ◽  
Vol 191 (1) ◽  
pp. 339-348 ◽  
Author(s):  
Atsushi Fukushima ◽  
Ping Yin ◽  
Maho Ishida ◽  
Nobuhiro Sugiyama ◽  
Jun Arita
Keyword(s):  
Third Ventricle ◽  
Acute Effect ◽  
Suppressive Effect ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Indwelling Catheter ◽  
Lh Surge ◽  
Gnrh Neurons ◽  
Double Immunohistochemical Staining ◽  
Lh Secretion

During lactation, the suckling stimulus exerts profound influences on neuroendocrine regulation in nursing rats. We examined the acute effect of pup removal on the estrogen-induced surge of LH secretion in ovariectomized lactating rats. Lactating and nonlactating cyclic female rats were given an estradiol-containing capsule after ovariectomy, and blood samples were collected through an indwelling catheter for serum LH determinations. In lactating, freely suckled ovariectomized rats, estrogen treatment induced an afternoon LH surge with a magnitude and timing comparable to those seen in nonlactating rats. Removal of pups from the lactating rats at 0900, 1100, or 1300 h, but not at 1500 h, suppressed the estrogen-induced surge that normally occurs in the afternoon of the same day. The suppressive effect of pup removal at 0900 h was completely abolished when the pups were returned by 1400 h. In contrast, pup removal was ineffective in abolishing the stimulatory effect of progesterone on LH surges. Double immunohistochemical staining for gonadotropin-releasing hormone (GnRH) and c-Fos, a marker for neuronal activation, revealed a decrease, concomitantly with the suppression of LH surges, in the number of c-Fos-immunoreactive GnRH neurons in the preoptic regions of nonsuckled rats. An LH surge was restored in nonsuckled rats when 0.1 μg oxytocin was injected into the third ventricle three times at 1-h intervals during pup removal. These results suggest that the GnRH surge generator of lactating rats requires the suckling stimulus that is not involved in nonlactating cyclic female rats.

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