Thesis etd-09122011-114510 |
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Thesis type
Tesi di laurea specialistica
Author
FERRARI, ALBERTO
URN
etd-09122011-114510
Thesis title
Characterization of the astroglia in an animal model of Alzheimer's Disease.
Department
SCIENZE MATEMATICHE, FISICHE E NATURALI
Course of study
NEUROBIOLOGIA
Supervisors
relatore Prof. Cattaneo, Antonino
correlatore Prof.ssa Capsoni, Simona
tutor Prof. Pasqualetti, Massimo
controrelatore Prof.ssa Dente, Luciana
correlatore Prof.ssa Capsoni, Simona
tutor Prof. Pasqualetti, Massimo
controrelatore Prof.ssa Dente, Luciana
Keywords
- AD11
- Alzheimer
- astrocytes
- astroglia
- glia
- NGF
Graduation session start date
29/09/2011
Availability
Full
Summary
Astrocytes are the most numerous cell type in the central nervous system, and one of its most important homeostatic elements, influencing neuronal activity. Moreover, astrocytes are involved in reaction to brain injury through reactive astrogliosis.
Although several studies report an induction of Nerve Growth Factor expression in astrocytes during brain damage and put it in relation to neuronal activity, no in vivo studies report about the effects that NGF, or its deprivation, can have on the astrocyte itself.
To this purpose, we used AD11 anti-NGF mice in which the expression of a recombinant antibody blocks the activity of mature NGF. Interestingly AD11 mice progressively develop an Alzheimer-like neurodegeneration which includes the deposition of β-in the hippocampus.
In this work, an analysis of astroglial morphology and Aβ deposits distribution in AD11 mice grouped by age was performed, to show the presence of astrocytic atrophy in mutants with respect to age-matched non transgenic mice. The correlations between AD11 astrocytes feature, Aβ deposition and the degree of NGF neutralization were also studied.
3D Images of astrocytes from the radiate and molecular layers of hippocampus were obtained by immunofluorescence and confocal microscopy, and analyzed using Bitplane's image elaboration software Imaris.
We found significant reduction in volume, surface area and number of branching points in younger AD11 mice with respect to aged-matched wild type mice. In older AD11 mice a decrease in branch length, area/volume ratio ratio was shown. A significant positive correlation was found between the amount of free NGF and astrocytic atrophy, but not with the of Aβ deposits. We therefore conclude that astroglial atrophy is present in AD11 mice, but it is induced by NGF neutralization and not triggered by amyloid protein formation.
Although several studies report an induction of Nerve Growth Factor expression in astrocytes during brain damage and put it in relation to neuronal activity, no in vivo studies report about the effects that NGF, or its deprivation, can have on the astrocyte itself.
To this purpose, we used AD11 anti-NGF mice in which the expression of a recombinant antibody blocks the activity of mature NGF. Interestingly AD11 mice progressively develop an Alzheimer-like neurodegeneration which includes the deposition of β-in the hippocampus.
In this work, an analysis of astroglial morphology and Aβ deposits distribution in AD11 mice grouped by age was performed, to show the presence of astrocytic atrophy in mutants with respect to age-matched non transgenic mice. The correlations between AD11 astrocytes feature, Aβ deposition and the degree of NGF neutralization were also studied.
3D Images of astrocytes from the radiate and molecular layers of hippocampus were obtained by immunofluorescence and confocal microscopy, and analyzed using Bitplane's image elaboration software Imaris.
We found significant reduction in volume, surface area and number of branching points in younger AD11 mice with respect to aged-matched wild type mice. In older AD11 mice a decrease in branch length, area/volume ratio ratio was shown. A significant positive correlation was found between the amount of free NGF and astrocytic atrophy, but not with the of Aβ deposits. We therefore conclude that astroglial atrophy is present in AD11 mice, but it is induced by NGF neutralization and not triggered by amyloid protein formation.
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