Abnormal motoneuron migration, differentiation, and axon outgrowth in spinal muscular atrophy

The role of heterotopic (migratory) motoneurons (HMN) in the pathogenesis of spinal muscular atrophy (SMA) is still controversial. We examined the occurrence and amount of HMN in spinal cord tissue from eight children with SMA (six with SMA-I and two with SMA-II). All affected subjects were carrying a homozygous deletion of exon 7 in the SMN1 gene. Unlike controls, virtually free from HMN, all SMA subjects showed a significant number of HMN at all levels of the spinal cord. Heterotopic neurons were hyperchromatic, located mostly in the ventral white matter and had no axon or dendrites. More than half of the HMN were very undifferentiated, as judged from their lack of immunoreactivity for NeuN and MAP2 proteins. Small numbers of more differentiated heterotopic neurons were also found in the dorsal and lateral white matter region. As confirmed by ultrastructural analysis, in situ end labeling (ISEL) and CD68 immunoreactivity, HMN in the ventral outflow were found to have no synapses, to activate microglial cells, and to eventually die by necrosis. An unbiased quantitative analysis showed a significant negative correlation between age of SMA subjects (a reflection of the clinical severity) and the number of HMN. Subjects who died at older ages had increased number of GFAP-positive astrocytes. Complementing our previous report on motoneuron apoptosis within the ventral horns in SMA, we now propose that abnormal migration, differentiation, and lack of axonal outgrowth may induce motoneuron apoptosis predominantly during early stages, whereas a slower necrosis-like cell death of displaced motoneurons which "escaped" apoptosis characterizes later stages of SMA

CHILD IN CONTEMPORARY CROATIAN SOCIETY

U Zagrebu je 12. prosinca 2009. održan simpozij »Dijete u suvremenome hrvatskom društvu«, koji su organizirali Hrvatsko pedijatrijsko društvo, Hrvatska akademija znanosti i umjetnosti, Ministarstvo zdravstva i socijalne skrbi i UNICEF za Hrvatsku. Predavači su prikazali važne podatke o teškoćama kojima su izložena djeca u Hrvatskoj. Naime, nove bolesti, koje su u suvremenom svijetu sve češće u djece, zahtijevaju od svih koji su uključeni u zdravstvenu zaštitu djece nove pristupe radu, što podrazumijeva i dodatnu edukaciju. To nisu bolesti uobičajene u svakodnevnoj liječničkoj praksi. Pristup društva, zbog raznolikosti teškoća s kojima se djeca suočavaju, može biti samo multidisciplinaran. Temeljni nacionalni interes društva je usmjeriti više pozornosti i financijska sredstva na zdravstvenu zaštitu djece, jer to osigurava opstanak i zdravu budućnost društva. Taj pristup zahtijeva nacionalni konsenzus i jasnu političku odluku svih odgovornih službi.The symposium on the topic »Child in contemporary Croatian society«, organized by Croatian Pediatric Society, Croatian Academy of Sciences and Arts, Ministry of health and social welfare and UNICEF Croatia Office, was held in Zagreb on December 12, 2009. The lecturers have shown important information on difficulties the children in Croatia are exposed to. Namely, diseases of the so called »new morbidity«, which are becoming more and more frequent in the contemporary world, demand a new approach of work from all who participate in healthcare for children, including additional education. These diseases are not part of a practitioner’s routine activity. Due to variety of problems children are exposed to, the approach can be only multidisciplinary. Basic national interest of every country (basic interest of every human society) should be to direct more attention and financial resources to the healthcare of children, which would ensure the existence and healthy future of the society. This approach requires a national consensus and clear political decision of all responsible official services

CHILD IN CONTEMPORARY CROATIAN SOCIETY

U Zagrebu je 12. prosinca 2009. održan simpozij »Dijete u suvremenome hrvatskom društvu«, koji su organizirali Hrvatsko pedijatrijsko društvo, Hrvatska akademija znanosti i umjetnosti, Ministarstvo zdravstva i socijalne skrbi i UNICEF za Hrvatsku. Predavači su prikazali važne podatke o teškoćama kojima su izložena djeca u Hrvatskoj. Naime, nove bolesti, koje su u suvremenom svijetu sve češće u djece, zahtijevaju od svih koji su uključeni u zdravstvenu zaštitu djece nove pristupe radu, što podrazumijeva i dodatnu edukaciju. To nisu bolesti uobičajene u svakodnevnoj liječničkoj praksi. Pristup društva, zbog raznolikosti teškoća s kojima se djeca suočavaju, može biti samo multidisciplinaran. Temeljni nacionalni interes društva je usmjeriti više pozornosti i financijska sredstva na zdravstvenu zaštitu djece, jer to osigurava opstanak i zdravu budućnost društva. Taj pristup zahtijeva nacionalni konsenzus i jasnu političku odluku svih odgovornih službi.The symposium on the topic »Child in contemporary Croatian society«, organized by Croatian Pediatric Society, Croatian Academy of Sciences and Arts, Ministry of health and social welfare and UNICEF Croatia Office, was held in Zagreb on December 12, 2009. The lecturers have shown important information on difficulties the children in Croatia are exposed to. Namely, diseases of the so called »new morbidity«, which are becoming more and more frequent in the contemporary world, demand a new approach of work from all who participate in healthcare for children, including additional education. These diseases are not part of a practitioner’s routine activity. Due to variety of problems children are exposed to, the approach can be only multidisciplinary. Basic national interest of every country (basic interest of every human society) should be to direct more attention and financial resources to the healthcare of children, which would ensure the existence and healthy future of the society. This approach requires a national consensus and clear political decision of all responsible official services