Neurotensin Enhances Locomotor Activity and Arousal and Inhibits Melanin-Concentrating Hormone Signaling

2019 ◽  
Vol 110 (1-2) ◽  
pp. 35-49 ◽  
Author(s):  
Talia Levitas-Djerbi ◽  
Dana Sagi ◽  
Ilana Lebenthal-Loinger ◽  
Tali Lerer-Goldshtein ◽  
Lior Appelbaum
Keyword(s):  
Locomotor Activity ◽  
Hormone Receptor ◽  
Behavioral Response ◽  
Hormone Signaling ◽  
Wild Type ◽  
Expression Levels ◽  
Physiological Processes ◽  
Melanin Concentrating Hormone ◽  
Behavioral Assays

Background: Hypothalamic neurotensin (Nts)-secreting neurons regulate fundamental physiological processes including metabolism and feeding. However, the role of Nts in modulation of locomotor activity, sleep, and arousal is unclear. We previously identified and characterized Nts neurons in the zebrafish hypothalamus. Materials and Methods: In order to study the role of Nts, nts mutant (nts–/–), and overexpressing zebrafish were generated. Results: The expression of both nts mRNA and Nts protein was reduced during the night in wild-type zebrafish. Behavioral assays revealed that locomotor activity was decreased during both day and night, while sleep was increased exclusively during the nighttime in nts–/– larvae. Likewise, inducible overexpression of Nts increased arousal in hsp70:Gal4/uas:Nts larvae. Furthermore, the behavioral response to light-to-dark transitions was reduced in nts–/– larvae. In order to elucidate potential contenders that may mediate Nts action on these behaviors, we profiled the transcriptome of 6 dpf nts–/– larvae. Among other genes, the expression levels of melanin-concentrating hormone receptor 1b were increased in nts–/– larvae. Furthermore, a portion of promelanin-concentrating hormone 1 (pmch1) and pmch2 neurons expressed the nts receptor. In addition, expression of the the two zebrafish melanin-concentrating hormone (Mch) orthologs, Mch1 and Mch2, was increased in nts–/– larvae. Conclusion: These results show that the Nts and Mch systems interact and modulate locomotor activity and arousal.

scholarly journals Role of the INDETERMINATE DOMAIN Genes in Plants

2019 ◽  
Vol 20 (9) ◽  
pp. 2286 ◽  
Author(s):  
Manu Kumar ◽  
Dung Thi Le ◽  
Seongbin Hwang ◽  
Pil Joon Seo ◽  
Hyun Uk Kim
Keyword(s):  
Plant Architecture ◽  
Genetic Characterization ◽  
Sugar Metabolism ◽  
Hormone Signaling ◽  
Biological Functions ◽  
Transcription Factor Family ◽  
Physiological Processes ◽  
Ammonium Metabolism

The INDETERMINATE DOMAIN (IDD) genes comprise a conserved transcription factor family that regulates a variety of developmental and physiological processes in plants. Many recent studies have focused on the genetic characterization of IDD family members and revealed various biological functions, including modulation of sugar metabolism and floral transition, cold stress response, seed development, plant architecture, regulation of hormone signaling, and ammonium metabolism. In this review, we summarize the functions and working mechanisms of the IDD gene family in the regulatory network of metabolism and developmental processes.

scholarly journals Reduced-Beclin1-Expressing Mice Infected with Zika-R103451 and Viral-Associated Pathology during Pregnancy

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 608 ◽  
Author(s):  
Mohan Kumar Muthu Karuppan ◽  
Chet Raj Ojha ◽  
Myosotys Rodriguez ◽  
Jessica Lapierre ◽  
M. Javad Aman ◽  
...  
Keyword(s):  
Growth Factor ◽  
Susceptibility Gene ◽  
Neuronal Loss ◽  
Wild Type ◽  
Zikv Infection ◽  
Expression Levels ◽  
Pregnant Mice ◽  
Alpha Beta ◽  
Inflammatory Molecules

Here, we used a mouse model with defective autophagy to further decipher the role of Beclin1 in the infection and disease of Zika virus (ZIKV)-R103451. Hemizygous (Becn1+/−) and wild-type (Becn1+/+) pregnant mice were transiently immunocompromised using the anti-interferon alpha/beta receptor subunit 1 monoclonal antibody MAR1-5A3. Despite a low mortality rate among the infected dams, 25% of Becn1+/− offspring were smaller in size and had smaller, underdeveloped brains. This phenotype became apparent after 2-to 3-weeks post-birth. Furthermore, the smaller-sized pups showed a decrease in the mRNA expression levels of insulin-like growth factor (IGF)-1 and the expression levels of several microcephaly associated genes, when compared to their typical-sized siblings. Neuronal loss was also noticeable in brain tissues that were removed postmortem. Further analysis with murine mixed glia, derived from ZIKV-infected Becn1+/− and Becn1+/+ pups, showed greater infectivity in glia derived from the Becn1+/− genotype, along with a significant increase in pro-inflammatory molecules. In the present study, we identified a link by which defective autophagy is causally related to increased inflammatory molecules, reduced growth factor, decreased expression of microcephaly-associated genes, and increased neuronal loss. Specifically, we showed that a reduced expression of Beclin1 aggravated the consequences of ZIKV infection on brain development and qualifies Becn1 as a susceptibility gene of ZIKV congenital syndrome.

scholarly journals Conditional deletion of melanin-concentrating hormone receptor 1 from GABAergic neurons increases locomotor activity

2019 ◽  
Vol 29 ◽  
pp. 114-123 ◽  
Author(s):  
Melissa J. Chee ◽  
Alex J. Hebert ◽  
Nadege Briançon ◽  
Stephen E. Flaherty ◽  
Pavlos Pissios ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Hormone Receptor ◽  
Gabaergic Neurons ◽  
Conditional Deletion ◽  
Melanin Concentrating Hormone

Non-Canonical NF-Kb Signaling Regulates Hematopoietic Stem Cell Self-Renewal and Microenvironment Interactions

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 859-859 ◽  
Author(s):  
Chen Zhao ◽  
Yan Xiu ◽  
John M Ashton ◽  
Lianping Xing ◽  
Yoshikazu Morita ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Wild Type ◽  
Double Knockout ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Physiological Processes ◽  
Marrow Cells

Abstract Abstract 859 RelB and NF-kB2 are the main effectors of NF-kB non-canonical signaling and play critical roles in many physiological processes. However, their role in hematopoietic stem/progenitor cell (HSPC) maintenance has not been characterized. To investigate this, we generated RelB/NF-kB2 double-knockout (dKO) mice and found that dKO HSPCs have profoundly impaired engraftment and self-renewal activity after transplantation into wild-type recipients. Transplantation of wild-type bone marrow cells into dKO mice to assess the role of the dKO microenvironment showed that wild-type HSPCs cycled more rapidly, were more abundant, and had developmental aberrancies: increased myeloid and decreased lymphoid lineages, similar to dKO HSPCs. Notably, when these wild-type cells were returned to normal hosts, these phenotypic changes were reversed, indicating a potent but transient phenotype conferred by the dKO microenvironment. However, dKO bone marrow stromal cell numbers were reduced, and bone-lining niche cells supported less HSPC expansion than controls. Further, increased dKO HSPC proliferation was associated with impaired expression of niche adhesion molecules by bone-lining cells and increased inflammatory cytokine expression by bone marrow cells. Thus, RelB/NF-kB2 signaling positively and intrinsically regulates HSPC self-renewal and maintains stromal/osteoblastic niches and negatively and extrinsically regulates HSPC expansion and lineage commitment through the marrow microenvironment. Disclosures: No relevant conflicts of interest to declare.

MCH Neuron Activity Is Sufficient for Reward and Reinforces Feeding

2019 ◽  
Vol 110 (3-4) ◽  
pp. 258-270 ◽  
Author(s):  
Pelin Dilsiz ◽  
Iltan Aklan ◽  
Nilufer Sayar Atasoy ◽  
Yavuz Yavuz ◽  
Gizem Filiz ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Glucose Tolerance ◽  
Energy Homeostasis ◽  
Neuron Activity ◽  
Physiological Effects ◽  
Short Term ◽  
Direct Role ◽  
Reward Function ◽  
Melanin Concentrating Hormone

Background: Melanin-concentrating hormone (MCH)-expressing neurons have been implicated in regulation of energy homeostasis and reward, yet the role of their electrical activity in short-term appetite and reward modulation has not been fully understood. Objectives: We investigated short-term behavioral and physiological effects of MCH neuron activity manipulations. Methods: We used optogenetic and chemogenetic approaches in Pmch-cre transgenic mice to acutely stimulate/inhibit MCH neuronal activity while probing feeding, locomotor activity, anxiety-like behaviors, glucose homeostasis, and reward. Results: MCH neuron activity is neither required nor sufficient for short-term appetite unless stimulation is temporally paired with consumption. MCH neuronal activation does not affect short-term locomotor activity, but inhibition improves glucose tolerance and is mildly anxiolytic. Finally, using two different operant tasks, we showed that activation of MCH neurons alone is sufficient to induce reward. Conclusions: Our results confirm diverse behavioral/physiological functions of MCH neurons and suggest a direct role in reward function.

Role of ryanodine receptor mutations in cardiac pathology: more questions than answers?

2006 ◽  
Vol 34 (5) ◽  
pp. 913-918 ◽  
Author(s):  
N.L. Thomas ◽  
C.H. George ◽  
F.A. Lai
Keyword(s):  
Ryanodine Receptor ◽  
Ventricular Arrhythmias ◽  
Striated Muscle ◽  
Polymorphic Ventricular Tachycardia ◽  
Wild Type ◽  
Cell Interior ◽  
Cardiac Pathology ◽  
Physiological Processes ◽  
The Common

The RyR (ryanodine receptor) mediates rapid Ca2+ efflux from the ER (endoplasmic reticulum) and is responsible for triggering numerous Ca2+-activated physiological processes. The most studied RyR-mediated process is excitation–contraction coupling in striated muscle, where plasma membrane excitation is transmitted to the cell interior and results in Ca2+ efflux that triggers myocyte contraction. Recently, single-residue mutations in the cardiac RyR (RyR2) have been identified in families that exhibit CPVT (catecholaminergic polymorphic ventricular tachycardia), a condition in which physical or emotional stress can trigger severe tachyarrhythmias that can lead to sudden cardiac death. The RyR2 mutations in CPVT are clustered in the N- and C-terminal domains, as well as in a central domain. Further, a critical signalling role for dysfunctional RyR2 has also been implicated in the generation of arrhythmias in the common condition of HF (heart failure). We have prepared cardiac RyR2 plasmids with various CPVT mutations to enable expression and analysis of Ca2+ release mediated by the wild-type and mutated RyR2. These studies suggest that the mutational locus may be important in the mechanism of Ca2+ channel dysfunction. Understanding the causes of aberrant Ca2+ release via RyR2 may assist in the development of effective treatments for the ventricular arrhythmias that often leads to sudden death in HF and in CPVT.

scholarly journals BRCA2 Heterozygosity Delays Cytokinesis in Primary Human Fibroblasts

2009 ◽  
Vol 31 (3) ◽  
pp. 191-201
Author(s):  
Asta Björk Jonsdottir ◽  
Maaike P. G. Vreeswijk ◽  
Ron Wolterbeek ◽  
Peter Devilee ◽  
Hans J. Tanke ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Human Fibroblasts ◽  
Immunofluorescence Staining ◽  
Wild Type ◽  
Expression Levels ◽  
Brca2 Protein ◽  
Mrna Expression Levels

Background: Inherited mutations in the tumour suppressor gene BRCA2 greatly increase the risk of developing breast, ovarian and other types of cancers. So far, most studies have focused on the role of BRCA-pathways in the maintenance of genomic stability.In this study we investigated the potential role of the BRCA2 protein in cytokinesis in unmodified primary human fibroblast carrying a heterozygous mutation in the BRCA2 gene.Methods: Cell divisions were monitored with time lapse live-cell imaging. BRCA2 mRNA expression levels in BRCA2+/− and BRCA2+/+ cells were quantified with quantitative real-time polymerase chain reaction (qRT-PCR). To investigate the localization of the BRCA2 protein during cytokinesis, immunofluorescence staining using antibody directed against BRCA2 was carried out. Immunofluorescence staining was performed directly after live-cell imaging and cells with delayed cytokinesis, of which the co-ordinates were saved, were automatically repositioned and visualized.Results: We demonstrate that unmodified primary human fibroblasts derived from heterozygous BRCA2 mutation carriers show significantly prolonged cytokinesis.A Subset of the BRCA2+/− cells had delayed cytokinesis (40 min or longer) making the mean cell division time 6 min longer compared with BRCA2+/+ cells, 33 min versus 27 min, respectively. Lower BRCA2 mRNA expression levels were observed in the BRCA2 heterozygous samples compared with the BRCA2 wild type samples.The BRCA2 protein localizes and accumulates to the midbody during cytokinesis, and no difference was detected in distribution and localization of the protein between BRCA2+/− and BRCA2+/+ samples or cells with delayed cytokinesis and normal division time.Conclusion: The delayed cytokinesis phenotype of the BRCA2 heterozygous cells and localization of the BRCA2 protein to the midbody confirms that BRCA2 plays a role in cytokinesis. Our observations indicate that in a subset of cells the presence of only one wild type BRCA2 allele is insufficient for efficient cytokinesis.

Neurokinin-1 Antagonism Distinguishes the Role of Norepinephrine Transporter from Dopamine Transporter in Mediating Amphetamine Behaviors

Pharmacology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Padmanabhan Mannangatti ◽  
Durairaj Ragu Varman ◽  
Sammanda Ramamoorthy ◽  
Lankupalle D. Jayanthi
Keyword(s):  
Locomotor Activity ◽  
Ventral Striatum ◽  
Surface Expression ◽  
Norepinephrine Transporter ◽  
Wild Type ◽  
Kinase C ◽  
In The Wild ◽  
High Sequence Homology ◽  
Neurokinin 1

<b><i>Background:</i></b> Amphetamine (AMPH) and other psychostimulants act on the norepinephrine (NE) transporter (NET) and the dopamine (DA) transporter (DAT) and enhance NE and DA signaling. Both NET and DAT share anatomical and functional characteristics and are regulated similarly by psychostimulants and receptor-linked signaling pathways. We and others have demonstrated that NET and DAT are downregulated by AMPH and substance P/neurokinin-1 receptor (NK1R)-mediated protein kinase C pathway. <b><i>Objectives:</i></b> Since both NET and DAT are downregulated by AMPH and NK1R activation and share high sequence homology, the objective of the study was to determine the catecholamine transporter specificity in NK1R modulation of AMPH-induced behaviors. <b><i>Methods:</i></b> The effect of NK1R antagonism on AMPH-induced conditioned place preference (CPP) as well as AMPH-induced NET and DAT downregulation was examined using NET and DAT knockout mice (NET-KO and DAT-KO) along with their wild-type littermates. <b><i>Results:</i></b> Aprepitant (5 mg/kg i.p.) significantly attenuated AMPH (2 mg/kg i.p.)-induced CPP in the wild-type and DAT-KO but not in the NET-KO. Locomotor activity measured during the post-conditioning test (in the absence of AMPH) showed higher locomotor activity in DAT-KO compared to wild-type or NET-KO. However, the locomotor activity of all 3 genotypes remained unchanged following aprepitant. Additionally, in the ventral striatum of wild-type, the AMPH-induced downregulation of NET function and surface expression but not that of DAT was attenuated by aprepitant. <b><i>Conclusions:</i></b> The results from the current study demonstrate that aprepitant attenuates the expression of AMPH-induced CPP in DAT-KO mice but not in NET-KO mice suggesting a role for NK1R-mediated NET regulation in AMPH-induced behaviors.

scholarly journals Analyzing the Role of Receptor Internalization in the Regulation of Melanin-Concentrating Hormone Signaling

2013 ◽  
Vol 2013 ◽  
pp. 1-10
Author(s):  
Jay I. Moden ◽  
Katrina Haude ◽  
Robert Carroll ◽  
Andrew Goodspeed ◽  
Laurie B. Cook
Keyword(s):  
Receptor Internalization ◽  
Hormone Signaling ◽  
Melanin Concentrating Hormone
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