Down’s syndrome is a the phenotypic expression of the partial or total trisomy of the chromosome 21. DS patients display visual deficits, impaired odour identification, inappropriate sexual and aggressive behaviour. Moreover, they are affected by mental retardation, and, in the adulthood, may develop anatomo-pathological alterations similar to thos observed in the Alzheimer’s disease. The search for an animal model to study DS has led in recent years to the development of the segmental trisomic 16 mouse (Ts65Dn) in which only a segment of the chromosome 16 is triplicat¬ed, this segment is the homologous of the obligate region of the human chromosome 21. Con¬trary to the trisomic 16 mouse (Ts16), which normally die in utero, the Ts65Dn mouse survive even adulthood and have several behavioural abnormalities that can be compared to the deficits of DS patients. Ts65Dn mice show, in fact, deficits in spatial learning and memory, inappropriate sexual and aggressive behaviours adaptative behavioural deficits. Many of these behaviours are controlled in rodents by the nitric-oxide producing neuronal system, which is extended through the entire brain. NO-system is also involved in the development of Alzheimer’s disease in humans. The obligate region of the chromosome 21 and the segment of mouse chromosome 16 which is triplicated in the Ts65Dn mouse contain, among the other genes, the gene for the copper-zinc su¬peroxide dismutase (Cu/Zn SOD; SOD1), an antioxidant enzyme which is involved in both the production and in the removal of the excess of NO. This enzyme is considered as the first line in the defence against oxygen derived radicals that seem to be involved in the degenerative processes of some neurological disease as Huntington’s, Parkinson and Alzheimer disease. Several behavioural studies have been already performed on this animal model, confirming a very close parallelism with the DS behavioural deficits, on the contrary, only a few studies have inves¬tigated the neuroanatomical architecture of the Ts65Dn mouse brain. Our project will investigate the distribution of NO-producing and SOD1 producing systems in adult mice of Ts65Dn strain and of the wild type. Due to implications on sexual behaviour, the research will be performed on both sexes in order to see if a sexually dimorphic anormalities could be found. NOS and SOD1 producing elements will be evidenced by means of immunohistochemical tech¬niques to identify the presence of the protein within the cells (neurones or glial cells). The presence of synthesis for these proteins will be tested by non-radioactive in situ hybridization techniques. The reactions will be performed on coronal and parasagittal serial sections in order to have a clear illustration of the extent of putative changes. The specimens will be subsequently considered for computer-assisted quantification of the extension of the immunoreactive reaction product.

Alterations of NO-producing neuronal system and superoxide dismutase distribution in the brain of a murine model for Down Syndrome

PANZICA, Giancarlo;GOTTI, STEFANO;VERZE', Laura;VIGLIETTI, Carla Maria
1999

Abstract

Down’s syndrome is a the phenotypic expression of the partial or total trisomy of the chromosome 21. DS patients display visual deficits, impaired odour identification, inappropriate sexual and aggressive behaviour. Moreover, they are affected by mental retardation, and, in the adulthood, may develop anatomo-pathological alterations similar to thos observed in the Alzheimer’s disease. The search for an animal model to study DS has led in recent years to the development of the segmental trisomic 16 mouse (Ts65Dn) in which only a segment of the chromosome 16 is triplicat¬ed, this segment is the homologous of the obligate region of the human chromosome 21. Con¬trary to the trisomic 16 mouse (Ts16), which normally die in utero, the Ts65Dn mouse survive even adulthood and have several behavioural abnormalities that can be compared to the deficits of DS patients. Ts65Dn mice show, in fact, deficits in spatial learning and memory, inappropriate sexual and aggressive behaviours adaptative behavioural deficits. Many of these behaviours are controlled in rodents by the nitric-oxide producing neuronal system, which is extended through the entire brain. NO-system is also involved in the development of Alzheimer’s disease in humans. The obligate region of the chromosome 21 and the segment of mouse chromosome 16 which is triplicated in the Ts65Dn mouse contain, among the other genes, the gene for the copper-zinc su¬peroxide dismutase (Cu/Zn SOD; SOD1), an antioxidant enzyme which is involved in both the production and in the removal of the excess of NO. This enzyme is considered as the first line in the defence against oxygen derived radicals that seem to be involved in the degenerative processes of some neurological disease as Huntington’s, Parkinson and Alzheimer disease. Several behavioural studies have been already performed on this animal model, confirming a very close parallelism with the DS behavioural deficits, on the contrary, only a few studies have inves¬tigated the neuroanatomical architecture of the Ts65Dn mouse brain. Our project will investigate the distribution of NO-producing and SOD1 producing systems in adult mice of Ts65Dn strain and of the wild type. Due to implications on sexual behaviour, the research will be performed on both sexes in order to see if a sexually dimorphic anormalities could be found. NOS and SOD1 producing elements will be evidenced by means of immunohistochemical tech¬niques to identify the presence of the protein within the cells (neurones or glial cells). The presence of synthesis for these proteins will be tested by non-radioactive in situ hybridization techniques. The reactions will be performed on coronal and parasagittal serial sections in order to have a clear illustration of the extent of putative changes. The specimens will be subsequently considered for computer-assisted quantification of the extension of the immunoreactive reaction product.
PANZICA G.C.; GOTTI S.; VERZE' L.; VIGLIETTI PANZICA C.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/123357
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