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Cooperability
| Project leader: |
Assistant Professor Goran Sedmak |
| Project co-leader: |
Professor Nenad Sestan |
| Administering organization: |
University of Zagreb, School of Medicine,
Šalata 3, 10 000, Zagreb, Croatia |
| Partner Institution/Company: |
Yale University School of Medicine, Department of Neurobiology |
| Grant type: |
1C |
| Project title: |
Developmental origin and phenotypic profile of white matter interstitial neurons in the human brain |
| Project summary: |
White matter interstitial neurons (WMIN) are large, yet insufficiently explored population of neurons located in the gyral white matter. This neuronal population is phylogenetically conserved and present in various animal species such as rodents, carnivores and primates. Their role, developmental origin, number, morphological and molecular profile are still debated. It has been proposed that WMIN are remnants of the transient fetal subplate zone. However, the exact number and subpopulations which survive into adulthood are still unknown. They are present in all parts of the cerebral cortex with varying density and distribution. WMIN have been linked with many important functions in the human brain such as regulating blood flow or sleep cycle. Furthermore, WMIN have been implicated in the etiopathogenesis of the many human brain disorders such as epilepsy, schizophrenia, bipolar disorder, depression, Alzheimer’s disease and multiple sclerosis. Although this neuronal population has important role in the proper functioning of the human brain, very little is known about its molecular and transcriptional profile. There are no studies in the human brain dealing with the transcriptome of this neuronal population. In order to better understand its role in normal and pathological functioning of the human brain a normative data about its origin, number, distribution, morphological and molecular profile needs to be generated. The goal of this proposal is to investigate in detail the number and regional differences in the distribution of WMIN; elucidate developmental origin of WMIN and to characterize morphological and molecular profile. In order to achieve these goals we will use combination of classical and novel methods such as: isotropic fractionator for neural quantification; single-cell RNAseq in order to determine transcriptional profile of WMIN; Neurolucida system for morphological reconstruction and in-situ hybridization and immunohistochemistry. Proposed research will be conducted at Croatian Institute for Brain Research, University of Zagreb School of Medicine and Department of Neurobiology, Yale University School of Medicine. The tissue used in the proposed research is available through Zagreb Neuroembryological Collection, located at Croatian Institute for Brain Research, and Brain Collection of Professor Nenad Sestan at Yale University. |
| Hrvatski sažetak: |
Intersticijski neuroni bijele tvari (WMIN)su mnogobrojna, ali nedovoljno istražena populacija neurona smještena u bijeloj tvari moždanih vijuga. Ova populacija neurona je filogenetski očuvana i prisutna u različitim vrstama (npr. u glodavcima, mesožderima, primatima). Njihova uloga, razvojno porijeklo, broj, morfologija i molekularni profil još uvijek nisu u potpunosti razjašnjeni. Predloženo je da su WMIN ostaci populacije neurona u prolaznoj fetalnoj zoni subplate. No, točan broj i subpopulacije koje prežive još uvijek nisu poznate. WMIN se nalaze u svim dijelovima moždane kore u različitim udjelima. Povezani su s mnogim važnim funkcijama ljudskog mozga kao što su regulacija protoka krvi i ciklusa spavanja. Nadalje. WMIN su povezani i s etiopatogenezom mnogih bolesti mozga kao što su epilepsija, shizofrenija, bipolarni poremećaj, depresija, Alzheimerova bolest i multipla skleroza. Iako ova populacija neurona ima važnu ulogu u normalnom radu ljudskog mozga, jako malo je poznato o njihovom molekularnom i transkripcijskom profilu. Trenutačno ne postoji studija o transkriptomu WMIN. Kako bismo bolje razumjeli ulogu WMIN u normalnom i patološkom funkcioniranju mozga potrebno je stvoriti normativne podatke o njihovom porijeklu, broju, distribuciji, morfološkom i molekularnom profilu. Cilj ovog prijedloga je detaljno istražiti broj i regionalne razlike u distribuciji WMIN, otkriti razvojno porijeklo, karakterizirati morfološki i molekularni profil. Kako bismo ostvarili ove ciljeve koristiti ćemo kombinaciju klasičnih i novih metoda kao što su izotropni frakcionator za kvantifikaciju broja neurona, RNAseq pojedinačnih neurona za otkrivanje transkriptoma, neurolucida sustav za rekonstrukciju morfologije neurona, i in-situ hibridizaciju i imunohistokemiju. Predloženo istraživanje će se provesti na Hrvatskom institutu za istraživanje mozga Medicinskog fakulteta Sveučilišta u Zagrebu i Odsjeku za neuroznanost Medicinskog fakulteta Sveučilišta Yale. Tkivo predviđeno za korištenje u studiji dostupno je kroz Zagrebačku neuroembriološku zbirku i Zbirku mozgova profesora Šestana na Sveučilištu Yale. |
| Amount requested from UKF: |
300.000,00 |
| Amount of matching funding: |
60.000,00 |
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