8 research outputs found
Dijete je gradu festival
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
Neuronal migration and cortical migratory disorders
U ovom radu pružili smo pregled spoznaja o neurobioloÅ”koj osnovi poremeÄaja migracije koja je važna za njihovu klasifikaciju. Kortikalni neuroni raÄaju se u ventrikularnoj i subventrikularnoj zoni te prolaze dugaÄak put do svojeg konaÄnog odrediÅ”ta, rabeÄi dva osnovna mehanizma i puta migracije: (1) radijalnu migraciju, put uzduž radijalne glije i (2) tangencijalnu, najvjerojatnije āneurofilnuā migraciju. Tijek migracije je složen i može biti poremeÄen utjecajem razliÄitih genetskih i vanjskih Äimbenika. PoremeÄaj proliferacije u ventrikularnoj zoni dovodi do znaÄajnih malformacija, kao Å”to je shizencefalija, a poremeÄaj samog poÄetka migracije uslijed genetskih abnormalnosti (mutacija FILAMIN1 gena) dovodi do periventrikularne nodularne heterotopije i strukturnih promjena vidljivih na slikovnim prikazima magnetskom rezonancijom (MRI). TipiÄni poremeÄaj migracije je lizencefalija tipa 1 koja se trenutno ubraja u spektar poremeÄaja agirija-pahigirija-ābandā heterotopija. Ova skupina poremeÄaja uzrokovana je mutacijama gena LIS1 i DCX (XLIS), a povezana je s Miller-Diekerovim, Lennox-Gastaut sindromom i epilepsijom. PoremeÄaji kasnijih faza migracije uzrokuju lizencefaliju tipa 2 (kompleks ācobblestoneā), koja je povezana s Walker-Warburgovim sindromom, makrocefalijom, malformacijom mrežnice, poremeÄajem miÅ”iÄ-oko-mozak i Fukuyama kongenitalnom miÅ”iÄnom distrofijom. Zellwegerov sindrom je karakteriziran patomorfoloÅ”ki polimikrogirijom i biokemijski grjeÅ”kom mithondrijskih putova desaturacije. PoremeÄaji kasne migracije pokazuju strukturne promjene vidljive MRI-om, koje su ograniÄene na moždanu koru. Drugi migracijski poremeÄaj, fokalna kortikalna displazija, Äesto je prisutna kod rezistentnih oblika epilepsije, a kod dijagnostike je od posebne koristi MRI visoke rezolucije (3T). Genetski testovi zajedno s MRI-om otvaraju nove moguÄnosti za ranu dijagnostiku i poboljÅ”ani pristup u lijeÄenju poremeÄaja migracije.In this review we outline the neurobiological basis for classification of cortical migratory disorders. Neurons of the human cortex are born in the ventricular and subventricular zone and migrate for a long distance to reach their final point of destination in the cortex, using two types of migratory routes and mechanisms: (1) radial migration along radial glia and (2) tangential, presumably āneurophilicā migration. The process of migration is complex and may be disturbed by various genetic and extrinsic factors. The disturbances of proliferation in the ventricular zone result in major malformations such as schizencephaly, while the failure of onset of migration results in periventricular nodular heterotopia with characteristic abnormalities in magnetic resonance imaging (MRI) and with genetic aberration in the background (FILAMIN1 gene mutation). The typical migratory disorder is lissencephaly type I caused by defect of ongoing migration. The lissencephaly type I is currently included in agyria-pachigyria band spectrum disorders. This group of disorders is caused by mutations of LIS1 and DCX (XLIS) gene mutations associated with Miller-Dieker syndrome, Lennox-Gastaut syndrome and epilepsy. The defects of late phases of migration cause lissencephaly type II, cobblestone complex, which is associated with Walker-Warburg syndrome, macrocephaly, retinal malformation, muscle-eye-brain disease and Fukuyama congenital muscular dystrophy. Zellweger syndrome is morphologically characterized by polymicrogyria and biochemically by defects of the mitochondrial desaturation pathway. The disorders with later migration failure show abnormal MRI restricted to the cortex. Another migratory disorder, focal cortical dysplasia, is a frequent cause of drug resistant epilepsy. An especially helpful diagnostic tool for migratory disorders is high resolution (3T) MRI. Genetic testing together with detailed MRI of migratory disorders opens new perspectives for early detection and improved treatment of migratory disorders