scholarly journals Regulation of Serotonin 1A Receptor SUMOylation by SENP2 and PIASxα

2021 ◽  
Vol 22 (24) ◽  
pp. 13176
Author(s):  
Sugandha Gupta ◽  
Mengya Wang ◽  
Yoshiaki Azuma ◽  
Nancy A. Muma
Keyword(s):  
Membrane Fraction ◽  
Acute Treatment ◽  
Neuropsychiatric Disorders ◽  
Depression And Anxiety ◽  
Protein Inhibitor ◽  
Serotonin 1A Receptor ◽  
Cytoplasmic Fraction ◽  
Agonist Stimulation ◽  
Large Fluctuations ◽  
17Β Estradiol

Serotonin 1A receptors (5-HT1ARs) are implicated in the control of mood, cognition, and memory and in various neuropsychiatric disorders such as depression and anxiety. As such, understanding the regulation of 5-HT1ARs will inform the development of better treatment approaches. We previously demonstrated 5-HT1ARs are SUMOylated by SUMO1 in the rat brain. Agonist stimulation increased SUMOylation and was further enhanced when combined with 17β-estradiol-3-benzoate (EB), which are treatments that cause the transient and prolonged desensitization of 5-HT1AR signaling, respectively. In the current study, we identified the protein inhibitor of activated STAT (PIAS)xα as the enzyme that facilitates SUMOylation, and SENP2 as the protein that catalyzes the deSUMOylation of 5-HT1ARs. We demonstrated that PIASxα significantly increased in the membrane fraction of rats co-treated with EB and an agonist, compared to either the EB-treated or vehicle-treated groups. The acute treatment with an agonist alone shifted the location of SENP2 from the membrane to the cytoplasmic fraction, but it has little effect on PIASxα. Hence, two separate mechanisms regulate SUMOylation and the activity of 5-HT1ARs by an agonist and EB. The effects of EB on 5-HT1AR SUMOylation and signaling may be related to the higher incidence of mood disorders in women during times with large fluctuations in estrogens. Targeting the SUMOylation of 5-HT1ARs could have important clinical relevance for the therapy for several neuropsychiatric disorders in which 5-HT1ARs are implicated.

Acute treatment with 17β-estradiol attenuates astrocyte–astrocyte and astrocyte–neuron communication

Glia ◽  
2007 ◽  
Vol 55 (16) ◽  
pp. 1680-1689 ◽  
Author(s):  
Shilpa P. Rao ◽  
Sujit Kumar Sikdar
Keyword(s):  
Acute Treatment ◽  
17Β Estradiol

scholarly journals Does human serotonin-1A receptor polymorphism (rs6295) code for pain and associated symptoms in fibromyalgia syndrome?

Reumatismo ◽  
2021 ◽  
Vol 73 (1) ◽  
pp. 24-31
Author(s):  
S. Tanwar ◽  
B. Mattoo ◽  
U. Kumar ◽  
R. Dada ◽  
R. Bhatia
Keyword(s):  
Gene Polymorphism ◽  
Pain Intensity ◽  
Healthy Subjects ◽  
Fibromyalgia Syndrome ◽  
Rating Scale ◽  
Research Work ◽  
Pain Modulation ◽  
Mcgill Pain Questionnaire ◽  
Depression And Anxiety ◽  
Serotonin 1A Receptor

Genetic predisposition may play an important role in the development of fibromyalgia syndrome (FMS). Serotonin is known to be involved in pain modulation and serotonin-1A receptor plays a considerable role in determining the central 5-HT tone. Consequently, variation in 5-HT1A receptor gene (HTR1A) may be responsible for inter-individual variability in pain sensitivity and other clinical symptoms of FMS. Therefore, the objectives of this research work were to study the gene polymorphism of 5-HTR1A gene and to explore the correlation between rs6295 genotype (−1019C/G HTR1A) and duration of pain, pain intensity and pain related depression and anxiety, if any, in FMS. 5-HTR1A genotype for the C(-1019)G polymorphism was typed in 62 patients with FMS and 42 healthy subjects. Present pain intensity, components of pain and pain related depression and anxiety were assessed using the numerical pain rating scale, McGill pain questionnaire and Hamilton depression and anxiety rating scale respectively. 5-HTR1A gene was represented by three different genotypes, homozygous C/C, heterozygous C/G and homozygous G/G. Analysis of the 5-HTR1A gene showed a frequency of 58%, 31% and 11% for the C/C, C/G and G/G genotypes, respectively in FMS group. This proportion was 69%, 23% and 8% in healthy subjects. No significant correlation was observed between 5-HTR1A gene polymorphism and pain and related symptoms in FMS patients. To the best of our knowledge this is the first study which investigated the correlation between the 5-HTR1A gene polymorphism and pain intensity, the affective component of pain, pain related depression and anxiety in FMS.

scholarly journals Historical Course of Neuropsychiatric Effects of Lemon Balm (Melissa Officinalis L.) as a Medicinal Herb

2021 ◽  
Author(s):  
Javid Ghazizadeh ◽  
Reza Mohammadinasab ◽  
Nikolaj Travica ◽  
Saeed Sadigh-Eteghad ◽  
Mohammadali Torbati ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Ages ◽  
Neuropsychiatric Disorders ◽  
Therapeutic Effects ◽  
Depression And Anxiety ◽  
Melissa Officinalis ◽  
Lemon Balm ◽  
Beneficial Effects ◽  
15Th Century ◽  
History Of

Abstract Affective disorders have become prevalent and costly worldwide chronic conditions. Lemon Balm (Melissa Officinalis L.) is a medicinal plant with beneficial effects on neuropsychiatric disorders. Its potential to specifically treat conditions such as depression and anxiety has been investigated for over 20 centuries. Given the lack of a historical overview of lemon balm in mood disorders, the present review aimed to introduce the historical course of the neuro-psychiatric applications of lemon balm across the centuries. We investigated several viable medieval Arabic sources up to the 15th century, to distinguish the neuropsychiatric applications, especially anxiolytic and anti-depressive effects of lemon balm. In the early centuries, lemon balm was mainly prescribed to treat gastrointestinal disorders. Over time, physicians identified the efficient use of lemon balm in sadness, sleep disorders, anxiety, depression, epilepsy, ischemic stroke, amnesia, sciatalgia, and radicular neuropathy. Importantly, it was established that the therapeutic effects of lemon balm in the field of neuro-psychiatric diseases were emphasized by physicians during the Middle Ages. These findings have since been validated in human clinical trials. Lemon balm has also demonstrated the ability to be utilized in epilepsy, amnesia and ischemic stroke. Based on the extensive history of lemon balm in neuropsychiatry, future investigations could use this knowledge to extensively investigate the potential of lemon balm in neuropsychiatric disorders such as depression and anxiety, and possibly develop an efficient neuropsychiatric remedy.

scholarly journals 17β-Estradiol Modifies Nitric Oxide-Sensitive Guanylyl Cyclase Expression and Down-Regulates Its Activity in Rat Anterior Pituitary Gland

Endocrinology ◽  
2006 ◽  
Vol 147 (9) ◽  
pp. 4311-4318 ◽  
Author(s):  
Jimena P. Cabilla ◽  
María del Carmen Díaz ◽  
Leticia I. Machiavelli ◽  
Ariel H. Poliandri ◽  
Fernanda A. Quinteros ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pituitary Gland ◽  
Mrna Expression ◽  
Guanylyl Cyclase ◽  
Anterior Pituitary ◽  
Acute Treatment ◽  
Inhibitory Effect ◽  
Anterior Pituitary Gland ◽  
Cgmp Pathway ◽  
17Β Estradiol

Previous studies showed that 17β-estradiol (17β-E2) regulates the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP pathway in many tissues. Evidence from our laboratory indicates that 17β-E2 disrupts the inhibitory effect of NO on prolactin release, decreasing sGC activity and affecting the cGMP pathway in anterior pituitary gland of adult ovariectomized and estrogenized rats. To ascertain the mechanisms by which 17β-E2 affects sGC activity, we investigated the in vivo and in vitro effects of 17β-E2 on sGC protein and mRNA expression in anterior pituitary gland from immature female rats. In the present work, we showed that 17β-E2 acute treatment exerted opposite effects on the two sGC subunits, increasing α1 and decreasing β1 subunit protein and mRNA expression. This action on sGC protein expression was maximal 6–9 h after 17β-E2 administration. 17β-E2 also caused the same effect on mRNA expression at earlier times. Concomitantly, 17β-E2 dramatically decreased sGC activity 6 and 9 h after injection. These effects were specific of 17β-E2, because they were not observed with the administration of other steroids such as progesterone and 17α-estradiol. This inhibitory action of 17β-E2 on sGC also required the activation of estrogen receptor (ER), because treatment with the pure ER antagonist ICI 182,780 completely blocked 17β-E2 action. 17β-E2 acute treatment caused the same effects on pituitary cells in culture. These results suggest that 17β-E2 exerts an acute inhibitory effect on sGC in anterior pituitary gland by down-regulating sGC β1 subunit and sGC activity in a specific, ER-dependent manner.

Phospholipid Transfer from ER to the Peribacteroid Membrane in Soybean Nodules

1985 ◽  
Vol 40 (1-2) ◽  
pp. 73-79 ◽  
Author(s):  
R. B. Mellor ◽  
T. M. I. E. Christensen ◽  
S. Bassarab ◽  
D. Werner
Keyword(s):  
Membrane Fraction ◽  
Adenosine Triphosphatase ◽  
Rhizobium Japonicum ◽  
Choline Kinase ◽  
Cytoplasmic Fraction ◽  
Peribacteroid Membrane ◽  
Choline Phosphotransferase ◽  
Membrane Atpase ◽  
Phospholipid Transfer

Organelle membranes subfractionated from nodules of Glycine max differed in lipid compo­sition. Of the enzymes assembling phospholipids, choline kinase (EC 2.7.1.32) was recovered in the cytoplasmic fraction whereas CDP choline 1,2-diacylglyceride choline phosphotransferase (EC2.7.8.2) was located in the ER. When methyl [14C]CDP choline was supplied to nodules in vivo radioactivity was found in the ER. On longer labelling periods [14C]phosphatidylcholine spread into denser regions of the gradient, including the peribacteroid membrane (which surrounds the Rhizobium japonicum symbiont). [14C]Phosphatidylcholine was a notable component of such membranes. Adenosine triphosphatase (EC 3.6.1.3) activity in the peribacteroid membrane fraction was compared to that of other major organelle fractions. The peribacteroid membrane ATPase was equally active on pH 6.0 and 8.0, was stimulated by K+ and inhibited by DES, DCCD and MoO4. In these respects it was more similar to the ATPase activity in the ER and mitochondria than in tonoplast or cytoplasm. The results are discussed in relation to modes of peribacteroid membrane biogenesis, in­cluding enzyme modification.

scholarly journals Identification of Membrane Proteins in the Hyperthermophilic ArchaeonPyrococcus FuriosusUsing Proteomics and Prediction Programs

2001 ◽  
Vol 2 (5) ◽  
pp. 275-288 ◽  
Author(s):  
James F. Holden ◽  
Farris L. Poole II ◽  
Sandra L. Tollaksen ◽  
Carol S. Giometti ◽  
Hanjo Lim ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Membrane Fraction ◽  
Pyrococcus Furiosus ◽  
Cell Fractionation ◽  
Cytoplasmic Fraction ◽  
Atpase Subunit ◽  
Consensus Prediction ◽  
Associated Proteins ◽  
2D Gel ◽  
Membrane Components

Cell-free extracts from the hyperthermophilic archaeonPyrococcus furiosuswere separated into membrane and cytoplasmic fractions and each was analyzed by 2D-gel electrophoresis. A total of 66 proteins were identified, 32 in the membrane fraction and 34 in the cytoplasmic fraction. Six prediction programs were used to predict the subcellular locations of these proteins. Three were based on signal-peptides (SignalP, TargetP, and SOSUISignal) and three on transmembrane-spanning α-helices (TSEG, SOSUI, and PRED-TMR2). A consensus of the six programs predicted that 23 of the 32 proteins (72%) from the membrane fraction should be in the membrane and that all of the proteins from the cytoplasmic fraction should be in the cytoplasm. Two membrane-associated proteins predicted to be cytoplasmic by the programs are also predicted to consist primarily of transmembrane-spanningβ-sheets using porin protein models, suggesting that they are, in fact, membrane components. An ATPase subunit homolog found in the membrane fraction, although predicted to be cytoplasmic, is most likely complexed with other ATPase subunits in the membrane fraction. An additional three proteins predicted to be cytoplasmic but found in the membrane fraction, may be cytoplasmic contaminants. These include a chaperone homolog that may have attached to denatured membrane proteins during cell fractionation. Omitting these three proteins would boost the membrane-protein predictability of the models to near 80%. A consensus prediction using all six programs for all 2242 ORFs in theP. furiosusgenome estimates that 24% of the ORF products are found in the membrane. However, this is likely to be a minimum value due to the programs’ inability to recognize certain membrane-related proteins, such as subunits associated with membrane complexes and porin-type proteins.

scholarly journals Behavioral and Metabolome Differences between C57BL/6 and DBA/2 Mouse Strains: Implications for Their Use as Models for Depression- and Anxiety-Like Phenotypes

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 128
Author(s):  
Michaela D. Filiou ◽  
Markus Nussbaumer ◽  
Larysa Teplytska ◽  
Christoph W. Turck
Keyword(s):  
Neuropsychiatric Disorders ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Molecular Characteristics ◽  
Depression And Anxiety ◽  
Metabolite Level ◽  
Metabolite Profiles ◽  
Total Antioxidant ◽  
Molecular Comparison ◽  
Plasma Metabolite

Mouse models are widely used to study behavioral phenotypes related to neuropsychiatric disorders. However, different mouse strains vary in their inherent behavioral and molecular characteristics, which needs to be taken into account depending on the nature of the study. Here, we performed a detailed behavioral and molecular comparison of C57BL/6 (B6) and DBA/2 (DBA) mice, two inbred strains commonly used in neuropsychiatric research. We analyzed anxiety-related and depression-like traits, quantified hippocampal and plasma metabolite profiles, and assessed total antioxidant capacity (ΤAC). B6 mice exhibit increased depression-like and decreased anxiety-related behavior compared to DBA mice. Metabolite level differences indicate alterations in amino acid, nucleotide and mitochondrial metabolism that are accompanied by a decreased TAC in B6 compared to DBA mice. Our data reveal multiple behavioral and molecular differences between B6 and DBA mouse strains, which should be considered in the experimental design for phenotype, pharmacological and mechanistic studies relevant for neuropsychiatric disorders.

Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: Relevance for neuropsychiatric disorders

2009 ◽  
Vol 198 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Ana M. Basso ◽  
Natalie A. Bratcher ◽  
Richard R. Harris ◽  
Michael F. Jarvis ◽  
Michael W. Decker ◽  
...  
Keyword(s):  
Animal Models ◽  
Knockout Mice ◽  
P2x7 Receptor ◽  
Neuropsychiatric Disorders ◽  
Depression And Anxiety ◽  
Behavioral Profile ◽  
Animal Models Of Depression

scholarly journals D-Serine in Neuropsychiatric Disorders: New Advances

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Andrea R. Durrant ◽  
Uriel Heresco-Levy
Keyword(s):  
Amino Acid ◽  
First Generation ◽  
Neuropsychiatric Disorders ◽  
Depression And Anxiety ◽  
Proof Of Concept ◽  
Glycine Site ◽  
Pharmacological Manipulation ◽  
Treatment Refractory ◽  
Dependent Processes ◽  
Major Drug

D-Serine (DSR) is an endogenous amino acid involved in glia-synapse interactions that has unique neurotransmitter characteristics. DSR acts as obligatory coagonist at the glycine site associated with the N-methyl-D-aspartate subtype of glutamate receptors (NMDAR) and has a cardinal modulatory role in major NMDAR-dependent processes including NMDAR-mediated neurotransmission, neurotoxicity, synaptic plasticity, and cell migration. Since either over- or underfunction of NMDARs may be involved in the pathophysiology of neuropsychiatric disorders; the pharmacological manipulation of DSR signaling represents a major drug development target. A first generation of proof-of-concept animal and clinical studies suggest beneficial DSR effects in treatment-refractory schizophrenia, movement, depression, and anxiety disorders and for the improvement of cognitive performance. A related developing pharmacological strategy is the indirect modification of DSR synaptic levels by use of compounds that alter the function of main enzymes responsible for DSR production and degradation. Accumulating data indicate that, during the next decade, we will witness important advances in the understanding of DSR role that will further contribute to elucidating the causes of neuropsychiatric disorders and will be instrumental in the development of innovative treatments.

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