Chronic psychosocial isolation alters hsp70/gr and hsp90/gr ratios in response to novel acute stress in rat hypothalamus

It is known that chronic psychosocial isolation (CPSI) exerts maladaptive effect on the hypothalamic-pituitary-adrenal (HPA) axis activity. Since the hypothalamus (HT) is a major driver of the HPA axis activity and since glucocorticoid receptor protein (GR) mediates HPA axis negative feedback particularly in this structure, we studied the effect of CPSI by following the expression of GR and its chaperones hsp70 and hsp90 in HT. Our results showed that the ratios of HSPs/GR set by the CPSI were altered in response to a novel acute stress, which indicated negative CPSI influence on GR functions in HT

Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner

The early postnatal environment is critical for its capacity to influence adult behavior, and is associated with traits of altered physiological and neurobiological function and long-term predisposition to depression. Here we describe the delayed effects of maternal deprivation (MD) in male and female Wistar pups on their physical development and behavior in adulthood in tasks designed to explore depressive-like (forced swimming test, FST), and anxiety-like behaviors (elevated plus maze, EPM). We observed that MD led to reduced body weight in adulthood, anxiety-like traits in the EPM test and increased activity in the phases of the FST. Particularly, a consistent sexual dimorphism was observed in the responses to MD. A lower increase in body weight during maturation of MD rats was more pronounced in males than in females. MD anxiogenic effects were more pronounced in females, while in FST only MD males showed a marked increase in swimming activity followed by decreased immobility

Association of female gonadal hormones and immunity in depression

In this study, we examined the influence of immunity on depressive-like behavior in females in the context of gonadal hormones. We used neuroinflammatory model of depression elicited by lipopolysaccharide (LPS) administration on naïve and ovariectomozed (OVX) females and examined the effects of estradiol (E2) and/or progesterone (P4) replacement therapy on Wistar rat behavior. LPS induced depressive–like behavior in both naïve and OVX females. Our behavioral data indicated that E2 and P4 applied alone had opposite effects compared to the E2/P4 combination. The supplementation of both hormones attenuates detrimental effects of LPSinduced inflammation, particularly through stimulation of noradrenergic transmission. Overall immune challenge with LPS is able to induce depressive-like behavior either of naïve or ovariectomized females, particularly depending on ovarian hormones background

Fluoxetine decreases the level of nuclear glucocorticoid receptor in wistar rat hippocampus under chronic stress

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and stress disorders. Glucocorticoids, key regulators of stress response, have diverse effects on cellular processes in the hippocampus. Beside non genomic pathways, glucocorticoids effects are mediated through activation of the glucocorticoid receptor (GR), a ligand activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. We analysed the GR protein level both, in the cytoplasmic and nuclear compartments in Wistar rat hippocampus, exposed to 3 week social isolation stress upon chronic fluoxetine treatment. Under chronic stress, corticosterone level was decreased compared to the control and treatment with fluoxetine did not change its level significantly in stressed animals. At the molecular level, fluoxetine significantly decreased the level of nuclear GR protein in the brain hippocampus of the chronically stressed rats. Fluoxetine reversed the nuclear level of GR disrupted by chronic psychosocial isolation (CPSI), but it failed to normalize HPA axis activity

Combined magnetic and structural characterization of hidrothermal bismuth ferrite (BiFeO3) nanoparticles

Bismuth ferrite (BiFeO3) was synthesized by hydrothermal method. The crystal and magnetic structures of BiFeO3 have been studied by means of X-ray diffraction and neutron powder diffraction at ambient temperature. Microstructure was analysed by scanning electron microscopy. Quantitative phase analysis by the Rietveld method was conducted and crystallite sizes of 27 nm were determined from the XRD line broadening. The magnetic structure of BiFeO3 is described by the G-type antiferromagnetic order with magnetic peak located at 4.6 Å and a noticeable magnetic contribution to a reflection located at 2.4 Å in the diffraction pattern. The values of the ordered magnetic moment of Fe ions μFe=3.8(1) μB, obtained at ambient conditions, are consistent with those determined earlier. The magnetic moments in the crystal plane z = const are arranged in parallel, changing the direction from [100] to [ 110 ] when moving from one to the other z = const plane. © 2018 Authors. Published by the International Institute for the Science of Sintering

Effects of ghrelin on protein expression of antioxidative enzymes and iNOS in the rat liver

Introduction: We investigated the effects of ghrelin on protein expression of the liver antioxidant enzymes superoxide dismutases (SODs), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), nuclear factor kappa B (NF kappa B) and inducible nitric oxide synthase (iNOS). Furthermore, we aimed to investigate whether extracellular regulated protein kinase (ERK1/2) and protein kinase B (Akt) are involved in ghrelin-regulated liver antioxidant enzymes and iNOS protein expression. Material and methods: Male Wistar rats were treated with ghrelin (0.3 nmol/5 mu l) injected into the lateral cerebral ventricle every 24 h for 5 days, and 2 h after the last treatment the animals were sacrificed and the liver excised. The Western blot method was used to determine expression of antioxidant enzymes, iNOS, phosphorylation of Akt, ERK1/2 and nuclear factor kappa B (NF kappa B) subunits 50 and 65. Results: There was significantly higher protein expression of CuZnSOD (p LT 0.001), MnSOD (p LT 0.001), CAT (p LT 0.001), GPx, (p LT 0.001), and GR (p LT 0.01) in the liver isolated from ghrelin-treated animals compared with control animals. In contrast, ghrelin significantly (p LT 0.01) reduced protein expression of iNOS. In addition, phosphorylation of NF kappa B subunits p65 and p50 was significantly (p LT 0.001 for p65; p LT 0.05 for p50) reduced by ghrelin when compared with controls. Phosphorylation of ERK1/2 and of Akt was significantly higher in ghrelin-treated than in control animals (p LT 0.05 for ERK1/2; p LT 0.01 for Akt). Conclusions: The results show that activation of Akt and ERK1/2 is involved in ghrelin-mediated regulation of protein expression of antioxidant enzymes and iNOS in the rat liver

Fluoxetine normalized nuclear phospho erk1/2 signaling in stressed females

A growing body of evidence indicates extracellular signal-regulated kinase (ERK1/2) participates in various stress-induced responses which isconsider to beinvolved in pathophysiology of depression. Surprisingly, the effect of antidepressants on ERKs is almost unexplored, particularly from the perspective of sexes.In the present study, we investigated the potential role of cytoplasm-nuclear distribution of phospho-ERK1/2 in the hippocampus of chronically stressed female and male Wistar rats and if those potential changes could be attenuated with chronic fluoxetine treatment. In females, stress induced cytosolic retention of phospho-ERKs, while in malesitpromoted the nuclear translocation of phospho-ERK 1/2. The effect of concomitant fluoxetine treatment was more pronounced in stressed females, with main focus on normalization of its nuclear phospho-ERK 1/2 levels

Glutarimidi - biološka aktivnost, opšti postupci za sintezu i fizičko-hemijske karakteristike

Glutarimides, 2,6-dioxopiperidines, are compounds that rarely occur in natural sources, but so far isolated ones exert widespread pharmacological activities, which makes them valuable as potential pharmacotherapeutics. Glutarimides act as androgen receptor antagonists, anti-inflammatory, anxiolytics, antibacterials, and tumor suppressing agents. Some synthetic glutarimide derivatives are already in use as immunosuppressive and sedative (e.g., thalidomide) or anxiolytics (buspirone) drugs. The wide applicability of this class of compounds, justify the interest of scientists to explore new pathways for its syntheses. General methods for synthesis of six-membered imide ring are presented in this paper. These methods include: a) reaction of dicarboxylic acids with ammonia or primary amine, b) reactions of cyclization: amido-acids, diamides, dinitriles, nitrilo-acids, amidonitriles, amido-esters, amidoacyl-chlorides or diacyl-chlorides, c) addition of carbon-monoxide on alpha,beta-unsaturated amides, d) oxidation reactions, e) Michael addition of active methylen compounds on methacrylamide or conjugated amides. Some of the described methods are used for closing glutarimide ring in syntheses of pharmacological active compounds sesbanimide and aldose reductase inhibitors (ARI). Analyses of the geometry, as well as, the spectroscopic analyses (NMR and FT-IR) of some glutarimides are presented due to their broad spectrum of pharmacological activity. To elucidate structures of glutarimides, geometrical parameters of newly synthesized tert-pentyl-1-benzyl-4-methyl-glutarimide-3-carboxylate (PBMG) are analyzed and compared with the experimental data from X-ray analysis for glutarimide. Moreover, molecular electrostatic potential (MEP) surface which is plotted over the optimized geometry to elucidate the reactivity of PBMG molecule is analyzed. The electronic properties of glutarimide derivatives are explained on the example of thalidomide. The Frontier Molecular Orbital (FMO) and their energies are presented, as well as the energy gap between them.U ovom radu dat je prikaz metoda za sintezu šestočlanih cikličnih imida. Glutarimidi, 2,6-dioksopiperidini, su značajna biološka jedinjenja i deluju kao antagonisti adrenogenih receptora, antiinflamatorni agensi, anksiolitici, antivirotici, antibiotici i agensi koji sprečavaju rast pojedinih vrsta tumora. Prikazana je i njihova spektralna analiza (FT-IR i NMR), zbog potvrde stukture, kao i analiza graničnih molekulskih orbitala koja daje prikaz elektronskih svojstava ovih molekula, što je važno zbog njihove biološke aktivnosti. Da bi se predstavila hemijska reaktivnost glutarimida predstavljen je molekulski elektronski potencijal (MEP) iz prethodno optimizovane geometrije reprezentativnog primera terc-pentil-1- -benzil-4-metil-glutarimid-3-karboksilata (skraćenica PBMG). Elektronska svojstva su objašnjena na primeru talidomida

Identification and Perceived Value of Ecosystem Services of Urban Green Areas. Case Study: Kamenički Park in Novi Sad, Serbia

Urban parks, as one of the most significant urban green areas (UGA), bring many direct or indirect benefits, including but not limited to ecosystem services (ES) (Mexia et al. 2018). These services are often generalized, unquantified and poorly supported by empirical evidence and their negative consequences – disservices are rarely mentioned (Roman et al., 2021; Pataki et al., 2011). In order to improve planning, design and management of UGA that can increase their environmental benefits (Xie et al. 2019), better understanding and additional field research of ES and disservices is required. As a result of a survey of employees of the Institute for Nature Conservation of Vojvodina Province that manages the park and on-site users, this study represents a research of the perceived value of generated ES on the example of Kamenički park in Novi Sad, as there are no studies on the actual value of those ES. After identifying major ES, the employees and users evaluated them by their perception on a scale of 1 – the ES is well provided, 2 – service is provided but can be enhanced and 3 – the service is not provided, but has potential. Employees mainly emphasized regulation and supporting services (regulation of air quality, noise reduction, wind protection, maintaining biodiversity), but also cultural services (educational role, recreation and enjoying nature, spiritual peace and prosperity). Users opted mainly for cultural services (recreation and enjoying nature and inspiration for culture, art and design), but also for supporting services like maintaining biodiversity. The specific location, valuable natural and cultural-historical characteristics of Kamenički park contribute to the provision of numerous ES, but also offer the opportunity to develop additional ones that are currently not represented or are not sufficiently provided. The opinions and needs of stakeholders and users regarding ES can be a guideline in planning in accordance with the ES, which is a step to sustainable cities. Quantifying the degree to which various ES are related to plant diversity and structure would provide evidence of the ability to manipulate designed ecosystems to maximize the benefits they provide to urban landscapes (Nighswander et al. 2021)

Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats

Considerable evidence shows an association of depression with the immune system and emphasizes the importance of gender in the etiology of the disease and the response to inflammatory stimuli. We examined the influence of immune-challenged systems on depressive-like behavior in female rats in the context of gonadal hormones. We used a neuroinflammatory model of depression elicited by lipopolysaccharide (LPS) administration on naive and ovariectomized (OVX) female rats, and examined the effects of estradiol (E2) and/or progesterone (P4) replacement therapy on animal behavior, as assessed by the forced swimming test (FST). We found that LPS and OVX increase immobility in the FST, while LPS also decreased body weight in naive female rats. Further, even though P4 application alone showed beneficial effects on the behavioral profile (it reduced immobility and increased climbing), supplementation of both hormones (E2 and P4) together to OVX rats failed to do so. When OVX rats were exposed to LPS-induced immune challenge, neither hormone individually nor their combination had any effect on immobility, however, their joint supplementation increased climbing behavior. In conclusion, our study confirmed that both LPS and OVX induced depressive-like behavior in female rats. Furthermore, our results potentiate P4 supplementation in relieving the depressive-like symptomatology in OVX rats, most likely through fine-tuning of different neurotransmitter systems. In the context of an activated immune system, the application of E2 and/or P4 does not provide any advantageous effects on depressive-like behavior