Croatian Institute for Brain Research

Salata, Croatia

Croatian Institute for Brain Research

Salata, Croatia
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Boban M.,University of Zagreb | Sarac H.,Croatian Institute for Brain Research | Mimica N.,University of Zagreb | Mladinov M.,Croatian Institute for Brain Research | And 7 more authors.
Translational Neuroscience | Year: 2010

Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) represent an important differential diagnostic problem in clinical practice. The identification for new biomarkers that would help establishing the diagnosis and primary cause of the dementia is therefore highly relevant. The aim of this study was to investigate the diagnostic accuracy of three potential CSF biomarkers, total tau protein (t-tau), tau protein phosphorylated at threonine 181 (p-tau181), and tau protein phosphorylated at serine 199 (p-tau199) in the differential diagnosis of AD and FTLD patients in relatively young age groups. The concentrations of the three CSF biomarkers were measured in 25 FTLD patients, 27 AD patients, and 25 non-demented (ND) subjects. The CSF concentrations of all three markers were significantly higher in AD than in FTLD cases (p < 0.001) or ND controls (p < 0.001). No difference was observed in FTLD compared to the ND group, except for p-tau181 (p = 0.028). When sensitivity was set at 85% or higher, specificity in differentiation between FTLD and AD patients reached 40% for t-tau, 37.5% for p-tau181 and 56% for p-tau199. Improvement of the diagnostic accuracy upon logistic regression analysis with t-tau and p-tau199 as independent variables showed that 22 out of 25 FTLD patients could be correctly classified. In conclusion, none of the markers per se fulfilled the criteria for the "ideal" marker (sensitivity and specificity higher than 85%). However, combination of t-tau and p-tau199 classified correctly 88% of FTLD patients, thus largely satisfying practical requirements. © Versita Sp. z o.o.


Sindic A.,Croatian Institute for Brain Research | Dobrivojevic M.,Croatian Institute for Brain Research | Hirsch J.R.,Pharis Biotec GmbH and CardioPep Pharma GmbH
Translational Neuroscience | Year: 2011

Natriuretic peptides (NPs) regulate salt and water homeostasis by inducing natriuresis and diuresis in the kidney. These actions in addition to those via the heart and vascular system play important roles in the regulation of blood pressure. In the central nervous system NPs play a significant role in neuronal development, synaptic transmission and neuroprotection. Currently, six different human NPs have been described: atrial natriuretic peptide (ANP), urodilatin (URO, renal natriuretic peptide), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) as well as guanylin and uroguanylin. ANP, URO and BNP activate the natriuretic peptide receptor A (NPR-A or guanylate cyclase A (GC-A)) while CNP activates natriuretic peptide receptor B (NPR-B or guanylate cyclase B (GC-B)). Guanylin and uroguanylin are known to activate guanylate cyclase C (GC-C). The receptors GC-A, GC-B, and GC-C are widely expressed in the human body. Currently, GC-B and CNP seems to have the highest expression in central nervous system compared to other NPs and their receptors. All known NPs generate intracellular cyclic GMP (cGMP) by activating their specific guanylate cyclase receptors. Subsequently, cGMP is able to activate protein kinase I or II (PKG I or II) and/or directly regulate transmembrane proteins such as ion channels, transporters and pumps. NPs also bind to the natriuretic peptide receptor C (also called clearance receptor NPR-C) which is a major pathway for the degradation of NPs and has no guanylate cyclase activity. In this review we will focus on new insights regarding the physiological effects of NPs in the brain, especially specific areas of their signaling pathways in neurons and glial cells. © Versita Sp. z o.o.


Fuller H.R.,RJAH Orthopaedic Hospital | Fuller H.R.,Keele University | Slade R.,Keele University | Jovanov-Milosevic N.,Croatian Institute for Brain Research | And 7 more authors.
Molecular and Cellular Neuroscience | Year: 2015

Understanding the intra- and extracellular proteins involved in the development of the corticospinal tract (CST) may offer insights into how the pathway could be regenerated following traumatic spinal cord injury. Currently, however, little is known about the proteome of the developing corticospinal system. The present study, therefore, has used quantitative proteomics and bioinformatics to detail the protein profile of the rat CST during its formation in the spinal cord. This analysis identified increased expression of 65 proteins during the early ingrowth of corticospinal axons into the spinal cord, and 36 proteins at the period of heightened CST growth. A majority of these proteins were involved in cellular assembly and organization, with annotations being most highly associated with cytoskeletal organization, microtubule dynamics, neurite outgrowth, and the formation, polymerization and quantity of microtubules. In addition, 22 proteins were more highly expressed within the developing CST in comparison to other developing white matter tracts of the spinal cord of age-matched animals. Of these differentially expressed proteins, only one, stathmin 1 (a protein known to be involved in microtubule dynamics), was both highly enriched in the developing CST and relatively sparse in other developing descending and ascending spinal tracts. Immunohistochemical analyses of the developing rat spinal cord and fetal human brain stem confirmed the enriched pattern of stathmin expression along the developing CST, and in vitro growth assays of rat corticospinal neurons showed a reduced length of neurite processes in response to pharmacological perturbation of stathmin activity. Combined, these findings suggest that stathmin activity may modulate axonal growth during development of the corticospinal projection, and reinforces the notion that microtubule dynamics could play an important role in the generation and regeneration of the CST. © 2015 Elsevier Inc.


PubMed | University of Zagreb, Croatian Institute For Brain Research Kaikaila@Helsinkifi, Croatian Institute for Brain Research and University of Helsinki
Type: Journal Article | Journal: Cerebral cortex (New York, N.Y. : 1991) | Year: 2015

Work on rodents demonstrated that steep upregulation of KCC2, a neuron-specific Cl


PubMed | Keele University, Croatian Institute for Brain Research and Andrews University
Type: | Journal: Molecular and cellular neurosciences | Year: 2015

Understanding the intra- and extracellular proteins involved in the development of the corticospinal tract (CST) may offer insights into how the pathway could be regenerated following traumatic spinal cord injury. Currently, however, little is known about the proteome of the developing corticospinal system. The present study, therefore, has used quantitative proteomics and bioinformatics to detail the protein profile of the rat CST during its formation in the spinal cord. This analysis identified increased expression of 65 proteins during the early ingrowth of corticospinal axons into the spinal cord, and 36 proteins at the period of heightened CST growth. A majority of these proteins were involved in cellular assembly and organization, with annotations being most highly associated with cytoskeletal organization, microtubule dynamics, neurite outgrowth, and the formation, polymerization and quantity of microtubules. In addition, 22 proteins were more highly expressed within the developing CST in comparison to other developing white matter tracts of the spinal cord of age-matched animals. Of these differentially expressed proteins, only one, stathmin 1 (a protein known to be involved in microtubule dynamics), was both highly enriched in the developing CST and relatively sparse in other developing descending and ascending spinal tracts. Immunohistochemical analyses of the developing rat spinal cord and fetal human brain stem confirmed the enriched pattern of stathmin expression along the developing CST, and in vitro growth assays of rat corticospinal neurons showed a reduced length of neurite processes in response to pharmacological perturbation of stathmin activity. Combined, these findings suggest that stathmin activity may modulate axonal growth during development of the corticospinal projection, and reinforces the notion that microtubule dynamics could play an important role in the generation and regeneration of the CST.


Boban M.,University of Zagreb | Malojcic B.,University of Zagreb | Mimica N.,University of Zagreb | Mimica N.,University Psychiatric Hospital | And 5 more authors.
Dementia and Geriatric Cognitive Disorders | Year: 2012

Aim: The aim of this study was standardization and validation of the Mini-Mental State Examination (MMSE) in the general Croatian aging population. Methods: Three-hundred and forty-four participants underwent the MMSE test, 217 cognitively healthy subjects without neurological and psychiatric disorders and 127 patients with mild cognitive impairment (MCI) or dementia. Results: The optimal cutoff point for screening of the general Croatian population (cognitively healthy vs. MCI and dementia) is 26/27; in the Croatian population aged ≥65 years, the cutoff point is 24/25, whereas for screening of highly educated persons (≥14 years of education) aged ≥65 years a higher cutoff point should be used (26/27). Conclusions: MMSE results when standardized and validated in a certain population might better contribute to recognition of the individuals at risk that should be directed to dementia outpatient clinics. Copyright © 2012 S. Karger AG, Basel.


Vladusic T.,University of Zagreb | Hrascan R.,University of Zagreb | Vrhovac I.,University of Zagreb | Kruslin B.,University of Zagreb | And 5 more authors.
Pathology Research and Practice | Year: 2010

Human testicular germ cell tumors (TGCTs) are histologically heterogenous neoplasms with a variable malignant potential. Two main groups of germ cell tumors occur in men: seminomas and nonseminomas. In the present study, a set of four tumor suppressor genes was investigated in testicular cancers. CDH1, APC, p53, and nm23-H1 genes were tested for loss of heterozygosity (LOH). Thirty-eight testicular germ cell tumors (17 seminomas and 21 nonseminomas) were analyzed by PCR using restriction fragment length polymorphism or the dinucleotide/tetranucleotide repeat polymorphism method. An allelic loss of p53 at exon 4 was detected in five nonseminomas, whereas LOH of p53 at intron 6 occurred in one of the seminoma and two of the nonseminoma samples. Allelic losses of the APC gene were present in three seminomas and one nonseminoma, whereas one seminoma and three nonseminomas showed LOH of CDH1. The analysis of allelic losses showed no common structural genetic alterations in tumor tissues, although a different pattern of LOH was observed between the two main histological groups of TGCTs. © 2009 Elsevier GmbH. All rights reserved.


Slade N.,Ruder Boskovic Institute | Zoric A.,Ruder Boskovic Institute | Horvat B.,French Institute of Health and Medical Research | Vuksic M.,Croatian Institute for Brain Research | And 2 more authors.
Immunobiology | Year: 2015

The aim of this study was to find out how NF-κB and Smad-mediated signaling influenced the expression of astrogliogenic versus neurogenic markers of brain development in U4C cells which were either enriched (Tg Jak-1) or deprived in Jak-1 molecule (Jak-1 KO). Genetically modified U4C cells were transfected with NF-kB reporter plasmid in order to follow its activation when cells were cotransfected with different combinations of Smads constructs.In wild type cells no significant activation of NF-κB was observed while genetically modified cells exhibited somewhat different pattern of NF-κB activation depending on the Smad constructs combination used. The absence of NF-κB activation in Jak-1 transgenic cells transfected with Smad-1 plus Smad-3 was accompanied by the appearance of apoptotic cells as revealed by DAPI staining. Smad-1 expression was undetectable in Jak-1 transgenic cells and was downregulated in wild type cells upon transfection with Smad-2. The absence of p65 nuclear translocation in Smad-2 transfected cells and the presence of Smad-4 in nucleus of the same cells indicates dichotomy in NF-κB and Smads mediated signaling pathways.The significance of this study is that helps to elucidate the point of collaboration among three different signaling pathways - Jak-1 mediated cytokine signaling, NF-κB and Smads mediated pathways. © 2014 Elsevier GmbH.


Grosic V.,Psychiatric Hospital Sveti Ivan | Grosic P.F.,University of Zagreb | Kalember P.,Croatian Institute for Brain Research | Kalember P.,University of Zagreb | And 6 more authors.
Neuropsychiatric Disease and Treatment | Year: 2014

Purpose: To investigate the correlates of a clinical therapeutic response by using the parameters measured by proton magnetic resonance spectroscopy after the administration of atypical antipsychotics. Patients and methods: Twenty-five antipsychotic-naïve first-episode patients with schizophrenia were monitored for 12 months. The patients were evaluated using 1H magnetic resonance spectroscopy in the dorsolateral prefrontal cortex and Positive and Negative Syndrome Scale, Clinical Global Impression Scale of Severity, Tower of London - Drexel University, Letter-Number Span Test, Trail Making Test A, and Personal and Social Performance Scale. They were administered atypical antipsychotics, starting with quetiapine. In the absence of a therapeutic response, another antipsychotic was introduced. Results: After 12 study months, the N-acetylaspartate/creatine (NAA/Cr) level did not significantly change at the whole-group level. Additional analysis revealed a significant rise in the NAA/Cr level in the study group that stayed on the same antipsychotic throughout the study course (P=0.008) and a significant drop in NAA/Cr in the study group that switched antipsychotics (P=0.005). On the whole-group level, no significant correlations between NAA/Cr values and other scores were found at either baseline or after 12 study months. Conclusion: One-year treatment with atypical antipsychotics administered to antipsychotic-naïve patients didn't result in a significant rise in the NAA/Cr ratio. However, a significant rise was witnessed in the study group in which a satisfactory therapeutic response had been achieved with a single antipsychotic administration. © 2014 Grošić et al.


PubMed | University of Zagreb, Ruder Boskovic Institute, Croatian Institute for Brain Research and French Institute of Health and Medical Research
Type: Journal Article | Journal: Immunobiology | Year: 2014

The aim of this study was to find out how NF-B and Smad-mediated signaling influenced the expression of astrogliogenic versus neurogenic markers of brain development in U4C cells which were either enriched (Tg Jak-1) or deprived in Jak-1 molecule (Jak-1 KO). Genetically modified U4C cells were transfected with NF-kB reporter plasmid in order to follow its activation when cells were cotransfected with different combinations of Smads constructs. In wild type cells no significant activation of NF-B was observed while genetically modified cells exhibited somewhat different pattern of NF-B activation depending on the Smad constructs combination used. The absence of NF-B activation in Jak-1 transgenic cells transfected with Smad-1 plus Smad-3 was accompanied by the appearance of apoptotic cells as revealed by DAPI staining. Smad-1 expression was undetectable in Jak-1 transgenic cells and was downregulated in wild type cells upon transfection with Smad-2. The absence of p65 nuclear translocation in Smad-2 transfected cells and the presence of Smad-4 in nucleus of the same cells indicates dichotomy in NF-B and Smads mediated signaling pathways. The significance of this study is that helps to elucidate the point of collaboration among three different signaling pathways - Jak-1 mediated cytokine signaling, NF-B and Smads mediated pathways.

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