DŠ

Dubravka Švob Štrac

Rudjer Boskovic Institute

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Nela Pivac

Rudjer Boskovic Institute

112

Matea Nikolac Perković

Rudjer Boskovic Institute

Gordana Nedić Erjavec

Rudjer Boskovic Institute

Lucija Tudor

Rudjer Boskovic Institute

Marcela Konjevod

Rudjer Boskovic Institute

Suzana Uzun

University of Zagreb

Oliver Kozumplik

Klinika za psihijatriju Vrapče

Danka Peričić

Rudjer Boskovic Institute

MŠ

Marina Šagud

University Hospital Centre Zagreb

Maja Jazvinšćak Jembrek

Catholic University of Croatia

Cooperative Institutions

University of Zagreb

University Hospital Centre Zagreb

Rudjer Boskovic Institute

University of Belgrade

Klinika za psihijatriju Vrapče

University of Osijek

Psychiatric Hospital Sveti Ivan

Universidade Federal de Minas Gerais

Ministry of Health

Medical University of Vienna

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Plasma Brain-Derived Neurotrophic Factor (BDNF) Concentration and BDNF/TrkB Gene Polymorphisms in Croatian Adults with Asthma

Journal of Personalized Medicine (2020)

Katherina Bernadette Sreter Sanja Popović‐Grle Marina Lampalo Marcela Konjevod Lucija Tudor

Brain-derived neurotrophic factor (BDNF) and its tropomyosin-related kinase B (TrkB) receptor might contribute to normal lung functioning and immune responses; however, their role in asthma remains unclear. Plasma BDNF concentrations, as well as BDNF and NTRK2 (TrkB gene) polymorphisms, were investigated in 120 asthma patients and 120 healthy individuals using enzyme-linked immunosorbent assay and polymerase chain reaction, respectively. The genotype and allele frequencies of BDNF Val66Met (rs6265) and NTRK2 rs1439050 polymorphisms did not differ between healthy individuals and asthma patients, nor between patients grouped according to severity or different asthma phenotypes. Although plasma BDNF concentrations were higher among healthy subjects carrying the BDNF Val66Met GG genotype compared to the A allele carriers, such differences were not detected in asthma patients, suggesting the influences of other factors. Plasma BDNF concentration was not affected by NTRK2 rs1439050 polymorphism. Asthma patients had higher plasma BDNF concentrations than control subjects; however, no differences were found between patients subdivided according to asthma severity, or Type-2, allergic, and eosinophilic asthma. Higher plasma BDNF levels were observed in asthma patients with aspirin sensitivity and aspirin-exacerbated respiratory disease. These results suggest that plasma BDNF may serve as a potential peripheral biomarker for asthma, particularly asthma with aspirin sensitivity.

rs6265

10.3390/jpm10040189

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The Association of the Polymorphisms in the FUT8-Related Locus with the Plasma Glycosylation in Post-Traumatic Stress Disorder

International Journal of Molecular Sciences (2023)

Lucija Tudor Gordana Nedić Erjavec Matea Nikolac Perković Marcela Konjevod Suzana Uzun

The molecular underpinnings of post-traumatic stress disorder (PTSD) are still unclear due to the complex interactions of genetic, psychological, and environmental factors. Glycosylation is a common post-translational modification of proteins, and different pathophysiological states, such as inflammation, autoimmune diseases, and mental disorders including PTSD, show altered N-glycome. Fucosyltransferase 8 (FUT8) is the enzyme that catalyzes the addition of core fucose on glycoproteins, and mutations in the FUT8 gene are associated with defects in glycosylation and functional abnormalities. This is the first study that investigated the associations of plasma N-glycan levels with FUT8-related rs6573604, rs11621121, rs10483776, and rs4073416 polymorphisms and their haplotypes in 541 PTSD patients and control participants. The results demonstrated that the rs6573604 T allele was more frequent in the PTSD than in the control participants. Significant associations of plasma N-glycan levels with PTSD and FUT8-related polymorphisms were observed. We also detected associations of rs11621121 and rs10483776 polymorphisms and their haplotypes with plasma levels of specific N-glycan species in both the control and PTSD groups. In carriers of different rs6573604 and rs4073416 genotypes and alleles, differences in plasma N-glycan levels were only found in the control group. These molecular findings suggest a possible regulatory role of FUT8-related polymorphisms in glycosylation, the alternations of which could partially explain the development and clinical manifestation of PTSD.

Fucosyltransferase

Glycome

10.3390/ijms24065706

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The association of GRIK3 polymorphism with alcoholism in the subjects of Croatian origin

Boris Kuzman Marina Morić Gordana Nedić Erjavec Matea Nikolac Perković Korona Nenadić Šviglin

Alcoholism is frequent and complex chronic disorder with numerous genetic and environmental risk factors. Genetic vulnerability to alcohol dependence is likely due to multiple contributing genes encoding proteins in many neurotransmitter systems and signal transduction pathways. Glutamatergic system has been implicated in acute and chronic effects of alcohol and represents a potential target for development of promising novel alcoholism therapeutics. In recent years, kainate ionotropic glutamate receptors have emerged as important targets of alcohol’s action in the brain. Namely, some reports suggested that Ser310Ala polymorphism in the GRIK3 gene, encoding the GluR7 subunit of kainate receptors, is associated with alcoholism. However, the fact that other studies failed to demonstrate these findings, might be explained by the differences in the origin of participants, as the role of genetic and environmental risk factors may be different in various populations. Hence, the aim of this study was to examine the allelic and genotypic association of GRIK3 functional polymorphism with alcohol dependence in subjects of Croatian origin. A total of 483 unrelated Caucasian subjects of Croatian origin, including 208 healthy control subjects and 275 patients diagnosed with alcohol dependence (DSM-IV criteria), stratified according to gender, age and nicotine dependence, were enrolled in the study. Following DNA extraction from the whole blood, genotyping of Ser310Ala GRIK 3 polymorphism (rs6691840) was performed by using TaqMan Real-Time allelic discrimination technique. No significant differences in the frequency of the genotypes and alleles for rs6691840 between alcohol-dependent and control individuals were detected. Moreover, in order to define the alcohol-related phenotypes more specifically, alcohol-dependent participants were additionally subdivided according to the early/late onset of alcohol abuse, presence/absence of aggressive behavior and lifetime suicide attempts. Although the distribution of genotypes and alleles did not differ between alcohol-dependent patients stratified by aggressive behavior or suicide attempts, the results demonstrated significant differences in the frequency of a homozygous CC genotype between the alcohol-dependent patients with the early onset (before 25 years of age) and patients with the late onset (after 25 years of age) of alcohol abuse. Further research is necessary to elucidate the role of GRIK3 gene in the development of alcoholism.

Alcohol Dependence

Kainate receptor

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The effects of persistent activation of GABA-A receptors by neurotransmitter GABA

Josipa Vlainić Dubravka Švob Štrac Maja Jazvinšćak Jembrek

Gamma-aminobutyric acid (GABA) has an important role in the transmission of neural information throughout all brain regions, and is involved directly and/or indirectly in the control of many vital functions. In particular, various brain functions depend on the balance between excitatory and inhibitory neurotransmission. Given that GABA is the main inhibitory neurotransmitter, changes in its level might lead to numerous neurological and psychiatric disorders. GABA achieves its physiological actions mostly through GABA-A receptors. Persistent activation of GABAA receptors by GABA, as well as by agonists and drugs facilitating the action of GABA, triggers regulatory changes in receptor expression and/or function that are relevant to physiological, pathological and pharmacological conditions. Therefore, the aim of our study was to better understand the effects and mechanisms that underlie adaptive changes at GABA-A receptors following their prolonged exposure to neurotransmitter GABA itself. Prolonged exposure of human embryonic kidney (HEK 293) cells stably expressing recombinant α1β2γ2S GABAA receptors to GABA (1 mM) enhanced the maximum number of [3H]flunitrazepam, [3H]muscimol and [3H]TBOB binding sites without affecting their affinity. The GABA-induced enhancement in the maximum number of benzodiazepine binding sites was reduced by bicuculline (100 μM), GABA-A receptor antagonist, and by cycloheximide (10 μL/mL), a protein synthesis inhibitor. In parallel, prolonged GABA treatment has not produced allosteric uncoupling of GABA and benzodiazepine binding sites as evidenced by unaltered GABA-induced potentiation of [3H]flunitrazepam binding. In conclusion, prolonged exposure of recombinant GABAA receptors to GABA results in enhancement of total receptor number, probably due to increased synthesis rather than decreased degradation of receptor proteins. Moreover, persistent activation of receptors by GABA has not resulted in functional uncoupling of GABA and benzodiazepine binding sites. Additional studies are needed to determine the functional implications of such changes, as well as relevance of obtained results to the development of tolerance and dependence.

Muscimol

Gamma-Aminobutyric Acid

GABA receptor antagonist

Zolpidem

Neurotransmitter receptor

Flunitrazepam

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Metabolomic and glycomic findings in posttraumatic stress disorder

Progress in Neuro-Psychopharmacology and Biological Psychiatry (2018)

Marcela Konjevod Lucija Tudor Dubravka Švob Štrac Gordana Nedić Erjavec Coral Barbas

Metabolome

Glycomics

Omics

Glycome

10.1016/j.pnpbp.2018.07.014

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Citations (44)

Platelet monoamine oxidase type B,MAOBintron 13 andMAOA-uVNTR polymorphism and symptoms of post-traumatic stress disorder

Stress (2016)

Dubravka Švob Štrac Zrnka Kovačić Petrović Matea Nikolac Perković Danica Umolac Gordana Nedić Erjavec

Post-traumatic stress disorder (PTSD), a disorder that develops following exposure to traumatic experience(s), is frequently associated with agitation, aggressive behavior and psychotic symptoms. Monoamine oxidase (MAO) degrades different biogenic amines and regulates mood, emotions and behavior, and has a role in the pathophysiology of various neuropsychiatric disorders. The aim of the study was to investigate the association between different symptoms occurring in PTSD [PTSD symptom severity assessed by the Clinician Administered PTSD Scale (CAPS), agitation and selected psychotic symptoms assessed by the Positive and Negative Syndrome Scale (PANSS)] and platelet MAO-B activity and/or genetic variants of MAOB rs1799836 and MAOA-uVNTR polymorphisms in 249 Croatian male veterans with PTSD. Our study revealed slightly higher platelet MAO-B activity in veterans with PTSD with more severe PTSD symptoms and in veterans with agitation, and significantly higher platelet MAO-B activity in veterans with more pronounced psychotic symptoms compared to veterans with less pronounced psychotic symptoms. Platelet MAO-B activity was associated with smoking but not with age. Genetic variants of MAOB rs1799836 and MAOA-uVNTR were not associated with agitation and selected psychotic symptoms in veterans with PTSD. A marginally significant association was found between MAOB rs1799836 polymorphism and severity of PTSD symptoms, but it was not confirmed since carriers of G or A allele of MAOB rs1799836 did not differ in their total CAPS scores. These findings suggest an association of platelet MAO-B activity, but a lack of association of MAOB rs1799836 and MAOA-uVNTR, with selected psychotic symptoms in ethnically homogenous veterans with PTSD.

Monoamine oxidase B

10.1080/10253890.2016.1174849

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Citations (15)

Neurosteroid dehydroepiandrosterone improves active avoidance retrieval and induces antidepressant-like behavior in rats

Neuroscience Letters (2017)

Janko Samardžić Boris Henčić Jasna Jančić Dragana Jadžić Milos Djuric

Allopregnanolone

10.1016/j.neulet.2017.09.013

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Citations (11)

The association between HT1A serothe association between 5-ht1a serotonin receptor gene polymorphism and extrapyramidal side effects in haloperidol-treated patients with schizophrenia

Mirko Grubor Dubravka Švob Štrac Maja Mustapić Maja Živković Alma Mihaljević-Peleš

Extrapyramidal symptoms

5-HT1A receptor

5-HT2A receptor

Association (psychology)

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Platelet Serotonin (5-HT) Concentration, Platelet Monoamine Oxidase B (MAO-B) Activity and HTR2A, HTR2C, and MAOB Gene Polymorphisms in Asthma

Biomolecules (2023)

Marcela Konjevod Katherina Bernadette Sreter Sanja Popović‐Grle Marina Lampalo Lucija Tudor

The complex role of the serotonin system in respiratory function and inflammatory diseases such as asthma is unclear. Our study investigated platelet serotonin (5-HT) levels and platelet monoamine oxidase B (MAO-B) activity, as well as associations with HTR2A (rs6314; rs6313), HTR2C (rs3813929; rs518147), and MAOB (rs1799836; rs6651806) gene polymorphisms in 120 healthy individuals and 120 asthma patients of different severity and phenotypes. Platelet 5-HT concentration was significantly lower, while platelet MAO-B activity was considerably higher in asthma patients; however, they did not differ between patients with different asthma severity or phenotypes. Only the healthy subjects, but not the asthma patients, carrying the MAOB rs1799836 TT genotype had significantly lower platelet MAO-B activity than the C allele carriers. No significant differences in the frequency of the genotypes, alleles, or haplotypes for any of the investigated HTR2A, HTR2C and MAOB gene polymorphisms have been observed between asthma patients and healthy subjects or between patients with various asthma phenotypes. However, the carriers of the HTR2C rs518147 CC genotype or C allele were significantly less frequent in severe asthma patients than in the G allele carriers. Further studies are necessary to elucidate the involvement of the serotonergic system in asthma pathophysiology.

Monoamine oxidase B

Pathophysiology of asthma

Monoamine oxidase A

10.3390/biom13050800

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Citations (5)

Introductory Chapter: GABA/Glutamate Balance: A Key for Normal Brain Functioning

InTech eBooks (2018)

Janko Samardžić Dragana Jadžić Boris Henčić Jasna Jančić Dubravka Švob Štrac

10.5772/intechopen.74023

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Citations (14)