Neuronal fibrillogenesis: Amyloid fibrils from primary neuronal cultures impair long-term memory in the crab Chasmagnathus

Amyloid β protein (Aβ) fibrillogenesis is considered one of the crucial steps of Alzheimer's disease (AD) pathogenesis. The effect of endogenous neuronal amyloid fibrils on memory processes is unknown. To investigate this issue, we first characterised the Aβ fibrillar aggregates secreted by cer...

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Publicado: 2003
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Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01664328_v147_n1-2_p73_Romano
http://hdl.handle.net/20.500.12110/paper_01664328_v147_n1-2_p73_Romano
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spelling paper:paper_01664328_v147_n1-2_p73_Romano2023-06-08T15:15:43Z Neuronal fibrillogenesis: Amyloid fibrils from primary neuronal cultures impair long-term memory in the crab Chasmagnathus Amyloid β protein Long-term memory Neuronal fibrillogenesis amyloid beta protein monomer thioflavine animal cell apoptosis article cell free system cell secretion conditioning controlled study crab electron microscopy fluorescence granule cell invertebrate learning long term memory memory nerve cell nerve cell culture nerve fiber nonhuman priority journal protein secretion training Amyloid β protein (Aβ) fibrillogenesis is considered one of the crucial steps of Alzheimer's disease (AD) pathogenesis. The effect of endogenous neuronal amyloid fibrils on memory processes is unknown. To investigate this issue, we first characterised the Aβ fibrillar aggregates secreted by cerebellar granule cells and then we evaluated the effect of neuronal fibrils on an invertebrate model of memory. An increase of fibril formation, assessed by Thioflavin T (ThT) fluorescence, was observed in the conditioned medium of apoptotic neurons during 48h of the apoptotic process. Moreover, the depolarisation-stimulated secretion of cerebellar granule cells contains monomers of endogenous Aβ, which undergo cell-free fibrillogenesis over several days of incubation. The pattern of single endogenous fibrils, examined by electron microscopy, was similar to that of synthetic Aβ while a tighter and more complex interfibrillar organization was observed in endogenous fibrils. The biological effect of neuronal fibrils was studied in a long-term memory (LTM) paradigm, namely the context-signal learning of the crab Chasmagnathus. Pre-training injection of neuronal fibril extract (protein concentration, 1μg/ml) induced amnesia in a dose-dependent manner. On the contrary, no effect on retention was observed with the administration of two orders higher doses (100μg/ml) of synthetic Aβ1-40. These results indicate that only naturally secreted fibrils, but not synthetic Aβ, clearly interfere with memory process. © 2003 Elsevier Science B.V. All rights reserved. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01664328_v147_n1-2_p73_Romano http://hdl.handle.net/20.500.12110/paper_01664328_v147_n1-2_p73_Romano
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Amyloid β protein
Long-term memory
Neuronal fibrillogenesis
amyloid beta protein
monomer
thioflavine
animal cell
apoptosis
article
cell free system
cell secretion
conditioning
controlled study
crab
electron microscopy
fluorescence
granule cell
invertebrate
learning
long term memory
memory
nerve cell
nerve cell culture
nerve fiber
nonhuman
priority journal
protein secretion
training
spellingShingle Amyloid β protein
Long-term memory
Neuronal fibrillogenesis
amyloid beta protein
monomer
thioflavine
animal cell
apoptosis
article
cell free system
cell secretion
conditioning
controlled study
crab
electron microscopy
fluorescence
granule cell
invertebrate
learning
long term memory
memory
nerve cell
nerve cell culture
nerve fiber
nonhuman
priority journal
protein secretion
training
Neuronal fibrillogenesis: Amyloid fibrils from primary neuronal cultures impair long-term memory in the crab Chasmagnathus
topic_facet Amyloid β protein
Long-term memory
Neuronal fibrillogenesis
amyloid beta protein
monomer
thioflavine
animal cell
apoptosis
article
cell free system
cell secretion
conditioning
controlled study
crab
electron microscopy
fluorescence
granule cell
invertebrate
learning
long term memory
memory
nerve cell
nerve cell culture
nerve fiber
nonhuman
priority journal
protein secretion
training
description Amyloid β protein (Aβ) fibrillogenesis is considered one of the crucial steps of Alzheimer's disease (AD) pathogenesis. The effect of endogenous neuronal amyloid fibrils on memory processes is unknown. To investigate this issue, we first characterised the Aβ fibrillar aggregates secreted by cerebellar granule cells and then we evaluated the effect of neuronal fibrils on an invertebrate model of memory. An increase of fibril formation, assessed by Thioflavin T (ThT) fluorescence, was observed in the conditioned medium of apoptotic neurons during 48h of the apoptotic process. Moreover, the depolarisation-stimulated secretion of cerebellar granule cells contains monomers of endogenous Aβ, which undergo cell-free fibrillogenesis over several days of incubation. The pattern of single endogenous fibrils, examined by electron microscopy, was similar to that of synthetic Aβ while a tighter and more complex interfibrillar organization was observed in endogenous fibrils. The biological effect of neuronal fibrils was studied in a long-term memory (LTM) paradigm, namely the context-signal learning of the crab Chasmagnathus. Pre-training injection of neuronal fibril extract (protein concentration, 1μg/ml) induced amnesia in a dose-dependent manner. On the contrary, no effect on retention was observed with the administration of two orders higher doses (100μg/ml) of synthetic Aβ1-40. These results indicate that only naturally secreted fibrils, but not synthetic Aβ, clearly interfere with memory process. © 2003 Elsevier Science B.V. All rights reserved.
title Neuronal fibrillogenesis: Amyloid fibrils from primary neuronal cultures impair long-term memory in the crab Chasmagnathus
title_short Neuronal fibrillogenesis: Amyloid fibrils from primary neuronal cultures impair long-term memory in the crab Chasmagnathus
title_full Neuronal fibrillogenesis: Amyloid fibrils from primary neuronal cultures impair long-term memory in the crab Chasmagnathus
title_fullStr Neuronal fibrillogenesis: Amyloid fibrils from primary neuronal cultures impair long-term memory in the crab Chasmagnathus
title_full_unstemmed Neuronal fibrillogenesis: Amyloid fibrils from primary neuronal cultures impair long-term memory in the crab Chasmagnathus
title_sort neuronal fibrillogenesis: amyloid fibrils from primary neuronal cultures impair long-term memory in the crab chasmagnathus
publishDate 2003
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01664328_v147_n1-2_p73_Romano
http://hdl.handle.net/20.500.12110/paper_01664328_v147_n1-2_p73_Romano
_version_ 1768546488348049408