Modelling the neurodevelopmental pathogenesis in neuropsychiatric disorders. Bioactive kynurenines and their analogues as neuroprotective agents-in celebration of 80th birthday of Professor Peter Riederer

Following introduction of the monoamine oxidase type B inhibitor selegiline for the treatment of Parkinson's disease (PD), discovery of the action mechanism of Alzheimer's disease-modifying agent memantine, the role of iron in PD, and the loss of electron transport chain complex I in PD, and development of the concept of clinical neuroprotection, Peter Riederer launched one of the most challenging research project neurodevelopmental aspects of neuropsychiatric disorders. The neurodevelopmental theory holds that a disruption of normal brain development in utero or during early life underlies the subsequent emergence of neuropsychiatric symptoms during later life. Indeed, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Classification of Diseases, 11th Revision categorize autism spectrum disorder and attention deficit hyperactivity disorder in neurodevelopmental disorders (NDDs). More and more evidence, especially from preclinical studies, is revealing that neurodevelopmental pathology is not limited to the diagnostic class above, but also contributes to the development of other psychiatric disorders such as schizophrenia, bipolar disorder, and obsessive-compulsive disorder as well as neurodegenerative diseases such as PD and Huntington's disease. Preclinical animal research is taking a lead in understanding the pathomechanisms of NDDs, searching for novel targets, and developing new neuroprotective agents against NDDs. This narrative review discusses emerging evidence of the neurodevelopmental etiology of neuropsychiatric disorders, recent advances in modelling neurodevelopmental pathogenesis, potential strategies of clinical neuroprotection using novel kynurenine metabolites and analogues, and future research direction for NDDs

Differential Changes in Expression of Stress- and Metabolic-related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal

Chronic morphine treatment and naloxone precipitated morphine withdrawal activates stress-related brain circuit and results in significant changes in food intake, body weight gain and energy metabolism. The present study aimed to reveal hypothalamic mechanisms underlying these effects. Adult male rats were made dependent on morphine by subcutaneous implantation of constant release drug pellets. Pair feeding revealed significantly smaller weight loss of morphine treated rats compared to placebo implanted animals whose food consumption was limited to that eaten by morphine implanted pairs. These results suggest reduced energy expenditure of morphine-treated animals. Chronic morphine exposure or pair feeding did not significantly affect hypothalamic expression of selected stress- and metabolic related neuropeptides - corticotropin-releasing hormone (CRH), urocortin 2 (UCN2) and proopiomelanocortin (POMC) compared to placebo implanted and pair fed animals. Naloxone precipitated morphine withdrawal resulted in a dramatic weight loss starting as early as 15-30 min after naloxone injection and increased adrenocorticotrophic hormone, prolactin and corticosterone plasma levels in morphine dependent rats. Using real-time quantitative PCR to monitor the time course of relative expression of neuropeptide mRNAs in the hypothalamus we found elevated CRH and UCN2 mRNA and dramatically reduced POMC expression. Neuropeptide Y (NPY) and arginine vasopressin (AVP) mRNA levels were transiently increased during opiate withdrawal. These data highlight that morphine withdrawal differentially affects expression of stress- and metabolic-related neuropeptides in the rat hypothalamus, while relative mRNA levels of these neuropeptides remain unchanged either in rats chronically treated with morphine or in their pair-fed controls

Brown adipose tissue in obesity: Fractalkine-receptor dependent immune cell recruitment affects metabolic-related gene expression.

Brown adipose tissue (BAT) plays essential role in metabolic- and thermoregulation and displays morphological and functional plasticity in response to environmental and metabolic challenges. BAT is a heterogeneous tissue containing adipocytes and various immune-related cells, however, their interaction in regulation of BAT function is not fully elucidated. Fractalkine is a chemokine synthesized by adipocytes, which recruits fractalkine receptor (CX3CR1)-expressing leukocytes into the adipose tissue. Using transgenic mice, in which the fractalkine receptor, Cx3cr1 gene was replaced by Gfp, we evaluated whether deficiency in fractalkine signaling affects BAT remodeling and function in high-fat-diet - induced obesity. Homo- and heterozygote male CX3CR1-GFP mice were fed with normal or fat enriched (FatED) diet for 10weeks. Interscapular BAT was collected for molecular biological analysis. Heterozygous animals in which fractalkine signaling remains intact, gain more weight during FatED than CX3CR1 deficient gfp/gfp homozygotes. FatED in controls resulted in macrophage recruitment to the BAT with increased expression of proinflammatory mediators (Il1a, b, Tnfa and Ccl2). Local BAT inflammation was accompanied by increased expression of lipogenic enzymes and resulted in BAT "whitening". By contrast, fractalkine receptor deficiency prevented accumulation of tissue macrophages, selectively attenuated the expression of Tnfa, Il1a and Ccl2, increased BAT expression of lipolytic enzymes (Atgl, Hsl and Mgtl) and upregulated genes involved thermo-metabolism (Ucp1, Pparg Pgc1a) in response to FatED. These results highlight the importance of fractalkine-CX3CR1 interaction in recruitment of macrophages into the BAT of obese mice which might contribute to local tissue inflammation, adipose tissue remodeling and regulation of metabolic-related genes

Information Patterns and News Bubbles in Hungary

The study is based on data from a representative survey conducted in Hungary in 2020, which examined the public’s con‐ sumption of political and public information. Using the survey data, the authors attempt to map the consumption patterns of the Hungarian audience, with a special focus on the relationship between party preferences and the consumption of the various news sources with different ideological backgrounds. The research aims to better understand the phenomenon of polarisation, which is increasingly observed on both the supply and demand sides of the Hungarian news media. The focus of the study is to examine news consumption patterns in Hungary and the relationship between political polarisation and news consumption. The authors analysed the prevalence of information bubbles in the Hungarian public sphere, where consumers are only exposed to the views of one political side without being confronted with information or opinions that differ. Particular attention is paid to a special category of the Hungarian media system, the grey‐zone media; they might seem to contribute greatly to the pluralism of the media system, but they are, in fact, strongly politically dependent. In addi‐ tion to the identified news consumption patterns, the study aims to shed light on the importance and problematic nature of this grey‐zone media category and to reveal how deeply the Hungarian public is actually dependent on the government

How Public Service Media Disinformation Shapes Hungarian Public Discourse

The structure of the illiberal Hungarian media system is well documented. Fewer publications address the question of how disinformation is reshaping public discourse in Hungary. The most important feature of disinformation in Hungary is that it is often generated and disseminated by the pro-government media. This is certainly unusual, as in other EU countries it is typically the fringe media which are responsible for spreading disinformation. The Russian war against Ukraine illustrates how the disinformation ecosystem works in Hungary, and it also reveals its devastating impact on democratic public discourse. Public service media play a prominent role in spreading disinformation. We were able to identify several false narratives in the period of the first year since the start of the war. In the first few months of the war, a key element of disinformation that was being spread in Hungary suggested that Ukraine had provoked the armed conflict. Later, the prevailing message was that only Hungary wanted peace, while the Western powers were interested in a continuation of the war. During autumn, the focus of the disinformation campaign increasingly shifted to the EU, disseminating an anti-EU message that was more concerned with the sanctions than the war. The pro-government media constantly told news consumers that the economic difficulties and the rise in energy prices had not been caused by the war launched by Russia but by the sanctions that the EU had imposed in response to the aggression. Public opinion research clearly shows the impact of these narratives on the perceptions of the Hungarian public. The polls readily capture how the Hungarian public’s opinion has changed over time. This study is primarily based on a content analysis of the relevant shows of the M1 public television channel, but we have also relied on some insights from public opinion polls to inform our analysis

Médiapluralizmus a digitális korban. A médiapluralizmus monitor alkalmazása az Európai unióban és a tagjelölt országokban 2023-ban. Országjelentés : Magyarország

This report presents the results of the implementation of the Media Pluralism Monitor in Hungary for the year 2023 (MPM2024). The MPM is a holistic tool aimed at assessing the risk to media pluralism in the EU member states and candidate countries. It considers legal, political, and economic variables relevant for analyzing the levels of media pluralism in a democratic society. The Media Pluralism Monitor has been implemented annually by the Centre for Media Pluralism and Media Freedom since 2013/2014.Ez a jelentés a Médiapluralizmus Monitor 2023. évi (MPM2024) magyarországi alkalmazásának eredményeit mutatja be. Az MPM egy holisztikus eszköz, amelynek célja a médiapluralizmust fenyegető kockázatok felmérése az uniós tagállamokban és a kiválasztott tagjelölt országokban. Az MPM azokat a jogi, politikai és gazdasági változókat veszi figyelembe, amelyek relevánsak a médiarendszerek pluralitásának elemzése szempontjából egy demokratikus társadalomban. A Médiapluralizmus és Médiaszabadság Központ 2013/2014 óta rendszeresen alkalmazza a médiapluralizmus-monitort.The Centre for Media Pluralism and Media Freedom is co-financed by the European Union

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently, a growing number of preclinical studies have revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among others. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)-kynurenine (KYN) metabolic system, which observably contributes to the development of pathological conditions including neurological and psychiatric disorders. This review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases

A versengés jutalmazásának hatása a nyáltesztoszteronszintre és a teljesítményre fiatal felnőtt férfiakban: A hiperversengés szerepe

Korábbi kutatások megmutatták, hogy versengő helyzetben a nagyobb jutalom megnövekedett fiziológiai arousallal jár. Mégis kevés tanulmány érintette a jutalmazás hatását a tesztoszteron (T) szintre, annak ellenére, hogy ez a hormon érzékenyen reagál a versengő helyzetekre és státuszváltozásokra. A jelen kutatás versengő helyzetben vizsgálta a nyáltesztoszteron és fiziológiai arousal (szívritmus, szívritmusvariabilitás) változásait fiatal felnőtt férfi mintán (N = 40, átlag életkor = 21.7 ± 2.3 év). A résztvev ők egy videojátékban versengtek egymással, ahol a páros egyik tagja nyert, a másik veszített a képességeknek és erőfeszítésnek megfelelően. A párosok véletlenszerű csoportosítása alapján résztvevők vagy egyenlő pénzjutalmat kaptak, vagy a győztes több jutalmat kapott, mint a vesztes (egyenlőtlen jutalom). A pszichofiziológiai és endokrinológiai méréseken túl a résztvevők versengéssel kapcsolatos attitűdjeit (hiperversengés, önfejlesztő versengés) és a versengő helyzetben mutatott hangulati változásait is felmértük kérdőívek segítségével. Az eredmények azt mutatták, hogy a versengés mindkét csoportban növelte mind a szubjektív, mind a fiziológiai arousalszintjét, ám a jutalom mértéke nem volt szignifikáns hatással a T szintre. A T szint csak a vesztes hiperversengőkben növekedett szignifikánsan. A kompetitív teljesítmény korrelált a győztesek és vesztesek T szintjével, illetve annak változásával, alátámasztva azt a korábbi megfigyelést, hogy a versengő teljesítmény és a T egymást kölcsönösen meghatározó kapcsolatban állnak. A kapott eredmények összefüggésben vannak a státuszinstabilitás-hipotézissel

Médiapluralizmus a digitális korban : a médiapluralizmus monitor alkalmazása az Európai Unióban, Albániában, Montenegróban, az Észak-macedón Köztársaságban, Szerbiában és Törökországban 2022-ben. Országjelentés : Magyarország

This report presents the results of the implementation of the Media Pluralism Monitor for the year 2022 (MPM2023) in Hungary. The MPM is a holistic tool geared at assessing the risks to media pluralism in EU member states and selected candidate countries (32 European countries in total, including Albania, Montenegro, the Republic of North Macedonia, Serbia, and Turkey). The MPM takes into account legal, political and economic variables that are relevant to analysing the levels of plurality of media systems in a democratic society. The Media Pluralism Monitor has been implemented, on a regular basis, by the Centre for Media Pluralism and Media Freedom, since 2013/2014.Ez a jelentés a Médiapluralizmus Monitor 2022. évi (MPM2023) magyarországi alkalmazásának eredményeit mutatja be. Az MPM egy holisztikus eszköz, amelynek célja a médiapluralizmust fenyegető kockázatok felmérése az uniós tagállamokban és a kiválasztott tagjelölt országokban (összesen 32 európai országban, köztük Albániában, Montenegróban, az Észak-macedón Köztársaságban, Szerbiában és Törökországban). Az MPM azokat a jogi, politikai és gazdasági változókat veszi figyelembe, amelyek relevánsak a médiarendszerek pluralitásának elemzése szempontjából egy demokratikus társadalomban. A Médiapluralizmus és Médiaszabadság Központ 2013/2014 óta rendszeresen alkalmazza a médiapluralizmus-monitort.The Centre for Media Pluralism and Media Freedom is co-financed by the European Unio