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| Marina Del Fiacco |
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Department of Cytomorphology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy
e-mail: dfiacco@unica.it |
Poster Presentation: |
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| Neurotrophin-like immunoreactivity in the human pre-term newborn, infant and adult cerebellum. |
| Marina Del Fiacco, Marina Quartu, Maria Pina Serra, Annalisa Manca, Paolo Follesa* and Maria Letizia Lai | |
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Departments of Cytomorphology and *Experimental Biology, University of Cagliari, Italy. |
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| The four mammalian neurotrophins (NTs) nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) regulate survival, proliferation and differentiation of a variety of neuronal populations during development. They further play roles in neuronal maintenance and repair, and in the modulation of synaptic efficacy in adult life. NTs and their receptors are widely expressed in the developing and adult cerebellum of experimental animals, where they affect cell survival and differentiation of granule cells and other cerebellar neuronal types, appear involved in cerebellar foliation, and protect granule cells from excitotoxic- and oxidative stress-mediated apoptosis. Reduced levels of some NTs have been correlated to impaired mouse cerebellar development in inherited neurological disorders and after early postnatal ethanol exposure, and have been reported in the cerebellum of Alzheimer?s disease patients. The relevance of NTs activity in the correct development and function of the cerebellum contrasts with the paucity of information regarding the occurrence and functional significance of these molecules in the human cerebellum, and their possible changes in pathology. This study provides data on the immunohistochemical occurrence of the four mammalian NTs in the normal human cerebellum at life stages spanning from prenatal age to adulthood. Cryostat sections of autoptic specimens were processed by the avidin-biotin-peroxidase complex immunohistochemical technique. Positive neuronal elements for each neurotrophin were observed in all specimens examined. Their distribution was uneven and showed regional differences among cerebellar lobules and folia. The paucity of samples examined did not allow their precise mapping, nor a clear-cut determination of age-related changes in their distribution and frequency. However, our observations indicate that (i) immunoreactivity to the four NTs occurs in the immature cells of the external granular layer in the premature newborns; (ii) NGF- and NT-3-positive cell bodies in the molecular layer persist throughout life; (iii) Purkinje cells immunoreactive for each neurotrophin are detectable in the pre-term newborn and cells positive for BDNF and NT-4 can be found in infancy; (iiii) perikarya immunoreactive for each neurotrophin are present in the granular layer in the pre-term newborn, whereas NT-4-positive ones can be detected also in infancy, and NGF- and NT-3-positive cell bodies persist throughout life; (iiiii) labelled neurons for each neurotrophin can be found in the deep cerebellar nuclei in pre-term age and NT-3-positive neurons occur in the dentate nucleus in adulthood. On the whole, these findings point to a decrease with age in the occurrence of neurotrophin-labelled cell bodies. By contrast, an increase with age was obvious in the fibre systems immunoreactive to BDNF in the arbor vitae, deep nuclei, and granular and Purkinje cortical layers. The present results indicate that NGF, BDNF, NT-4, and NT-3 are likely to be involved in development, differentiation, maintenance and repair of the neuronal circuitry in the human cerebellum. The simultaneous occurrence of the four NTs further suggests that parallel patterns of multiple neurotrophin expression may be significant in the accomplishment of their trophic activities on the cerebellar connectivity. |
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