Neuronal fibrillogenesis: amyloid fibrils from primary neuronal cultures impair long-term memory in the crab Chasmagnathus.
Amyloid beta protein (Abeta) 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 Abeta 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 48 h of the apoptotic process. Moreover, the depolarisation-stimulated secretion of cerebellar granule cells contains monomers of endogenous Abeta, 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 Abeta 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, 1 microg/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 (100 microg/ml) of synthetic Abeta1-40. These results indicate that only naturally secreted fibrils, but not synthetic Abeta, clearly interfere with memory process.
Romano
Arturo
A
Laboratorio de Neurobiología de la Memoria, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428, Argentina.
Serafino
Annalucia
A
Krasnowska
Ewa
E
Ciotti
Maria Teresa
MT
Calissano
Pietro
P
Ruberti
Francesca
F
Galli
Cinzia
C
D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology* / Q000648:ultrastructure; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal; D052160:Benzothiazoles; D003386:Brachyura; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry / Q000379:methods; D007150:Immunohistochemistry; D008297:Male; D008568:Memory / Q000187:drug effects*; D008854:Microscopy, Electron / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology / Q000648:ultrastructure; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000378:metabolism; D013997:Time Factors
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D017077:Culture Media, Conditioned; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C009462:thioflavin T; D011189:Potassium Chloride