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Cooperability
| Project leader |
Kostović Ivica |
| Project co-leader: |
Paško Rakić |
| Administering organization: |
School of Medicine University of Zagreb
Salata 3, 10 000 Zagreb, www.mef.hr ,
Croatian Institute for Brain Research, Salata 12, www.hiim.hr
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| Partner Institution/Company: |
Dept. of Neurobiology, School of Medicine, Yale University; Montreal Neurological Institute, McGill University |
| Grant type: |
1B |
| Project title: |
Neuroimaging, neurogenomics and pharmacogenomics of the frontal lobe connectivity: normal development and abnormalities in developmental cognitive disorders |
| Project summary: |
The objective of project is to supplement neuroimaging studies at the School of Medicine
University of Zagreb with neurogenomics (with Yale University) and functional neuroimaging
(with Montreal Neurological Institute and Harvard). This cutting-edge approach (genes –
structure – functions) is based on analysis of prefrontal cortical areas in normal development
and cognitive disorders, and developing protocols for genome-based pharmacotherapy of
depression.
The project develops new approach to studying abnormal development of cortical circuitry in
cognitive disorders (autism), introduces new technologies in Croatia, ensures research use of
new 3 Tesla MR, enhances return of scientists from Diaspora, and secures international grant
applications (FP7).
Specific aims are:
1) To analyze areal differentiation of human frontal (orbital, dorsolateral, and
precingulate) cortex and related nuclei (amygdala, thalamus) from fetal life to
adolescence, using developmental criteria for specification of cortical areas, layers,
modules and molecular phenotypes of pyramidal neurons. To identify cortical
pathways, areas and layers. To determine cellular and molecular correlates of gene
expression in prefrontal and language-related areas with focus on transient fetal
neurons, cytoarchitectonic zones and pyramidal neurons. To analyze cellular
determinants of cortical thickness and perinatal cortical reorganization. To compare
developmental and gene expression data obtained in humans with those obtained in
rhesus monkey and mouse.
2) To describe histological correlates of structural MRI changes in normal and disordered
cortex from fetal period to adolescence.
3) To combine MR spectroscopy with genomic analysis in studying frontal cortical areas
of young adolescents with depression, after antidepressant medication.
Methodology: Histological studies – immunocitochemistry, DiI, Golgi morphometry;
Neuroimaging – structural in vivo and in vitro MRI with 3D-volumetry, DTI tractography, fMRI;
Neurogenomics- overall gene expression analysis together with gene expression profiling of
specific brain regions by microarray technology, real-time PCR and in situ hybridization
Neuroproteomics – structures and functions related study of protein expression profile within
brain
Pharmacogenomics –proton MRS and microarray analysis.
The main contribution of the project is development of scientific infrastructure in Croatia (hightech
research with 3Tesla MR device).
We expect to: delineate sensitive periods in development of prefrontal connectivity and timing
of gene expression in principal neurons; unravel abnormalities of cortical circuitry underlying
cognitive disorders; and develop individualized treatment based on pharmacogenomics. The
project benefits Croatian biomedical centers by introducing neurogenomic tools. It also helps
combat brain disorders, which (by representing 30% of total health costs) have great
socioeconomic impact (depression-5% of population). The results will be communicated
through high impact publications, conferences and symposia. |
| Hrvatski sažetak: |
Cilj projekta je nadopuniti neuroimaging studije Medicinskog fakulteta Sveučilišta u Zagrebu sa neurogenomikom (sa Sveučilištom Yale) te funkcionalnim neuroimaging studijama (s Neurološkim institutom u Montrealu i Harvardu). Ovakav napredan pristup (geni – struktura – funkcija) zasnovan je na analizi prefrontalnih moždanih područja tijekom normalnog razvitka, kognitivnih bolesti te na razvitku protokola za, na genomu temeljenu, farmakoterapiju depresije. Glavni doprinos projekta razvitak je znanstvene infrastrukture u Hrvatskoj (visoka tehnologija u istraživanju sa 3Tesla MR uređajem). Projekt će koristiti hrvatskim biomedicinskim centrima uvođenjem neurogenomskih pristupa. Projekt razvija novi pristup u istraživanju poremećenog razvitka kortikalnih krugova u kognitivnim bolestima (autizam), uvodi novu tehnologiju u Hrvatsku, osigurava korištenje novog 3 Tesla MR uređaja u znanstvene svrhe, potiče povratak znanstvenika iz iseljeništva, te jamči međunarodne natječaje za novčane potpore (FP7).
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| Amount requested from UKF: |
200 000 € |
| Amount of matching funding: |
95 000 € |
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