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Characterization of the beta amyloid precursor protein-like gene in the central nervous system of the crab Chasmagnathus. Expression during memory consolidation.

ABSTRACT: BACKGROUND:Human ?-amyloid, the main component in the neuritic plaques found in patients with Alzheimer's disease, is generated by cleavage of the ?-amyloid precursor protein. Beyond the role in pathology, members of this protein family are synaptic proteins and have been associated with synaptogenesis, neuronal plasticity and memory, both in vertebrates and in invertebrates. Consolidation is necessary to convert a short-term labile memory to a long-term and stable form. During consolidation, gene expression and de novo protein synthesis are regulated in order to produce key proteins for the maintenance of plastic changes produced during the acquisition of new information. RESULTS:Here we partially cloned and sequenced the beta-amyloid precursor protein like gene homologue in the crab Chasmagnathus (cappl), showing a 37% of identity with the fruit fly Drosophila melanogaster homologue and 23% with Homo sapiens but with much higher degree of sequence similarity in certain regions. We observed a wide distribution of cappl mRNA in the nervous system as well as in muscle and gills. The protein localized in all tissues analyzed with the exception of muscle. Immunofluorescence revealed localization of cAPPL in associative and sensory brain areas. We studied gene and protein expression during long-term memory consolidation using a well characterized memory model: the context-signal associative memory in this crab species. mRNA levels varied at different time points during long-term memory consolidation and correlated with cAPPL protein levels CONCLUSIONS:cAPPL mRNA and protein is widely distributed in the central nervous system of the crab and the time course of expression suggests a role of cAPPL during long-term memory formation.

SUBMITTER: Fustinana MS

PROVIDER: S-EPMC2940927 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Characterization of the beta amyloid precursor protein-like gene in the central nervous system of the crab Chasmagnathus. Expression during memory consolidation.

Fustiñana Maria Sol MS Ariel Pablo P Federman Noel N Freudenthal Ramiro R Romano Arturo A

BMC neuroscience 20100901

<h4>Background</h4>Human β-amyloid, the main component in the neuritic plaques found in patients with Alzheimer's disease, is generated by cleavage of the β-amyloid precursor protein. Beyond the role in pathology, members of this protein family are synaptic proteins and have been associated with synaptogenesis, neuronal plasticity and memory, both in vertebrates and in invertebrates. Consolidation is necessary to convert a short-term labile memory to a long-term and stable form. During consolida ...[more]

PMID: 20809979

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Project description:Importance:Recent studies found that the concentration of amyloid-? (A?) fluctuates with the sleep-wake cycle. Although the amplitude of this day/night pattern attenuates with age and amyloid deposition, to our knowledge, the association of A? kinetics (ie, production, turnover, and clearance) with this oscillation has not been studied. Objective:To determine the association between A? kinetics, age, amyloid levels, and the A? day/night pattern in humans. Design, Setting, and Participants:We measured A? concentrations and kinetics in 77 adults aged 60 to 87 years with and without amyloid deposition by a novel precise mass spectrometry method at the Washington University School of Medicine in St Louis, Missouri. We compared findings of 2 orthogonal methods, enzyme-linked immunosorbent assay and mass spectrometry, to validate the day/night patterns and determine more precise estimates of the cosinor parameters. In vivo labeling of central nervous system proteins with stable isotopically labeled leucine was performed, and kinetics of A?40 and A?42 were measured. Interventions:Serial cerebrospinal fluid collection via indwelling lumbar catheter over 36 to 48 hours before, during, and after in vivo labeling, with a 9-hour primed constant infusion of 13C6-leucine. Main Outcomes and Measures:The amplitude, linear increase, and other cosinor measures of each participant's serial cerebrospinal fluid A? concentrations and A? turnover rates. Results:Of the 77 participants studied, 46 (59.7%) were men, and the mean (range) age was 72.6 (60.4-87.7) years. Day/night patterns in A? concentrations were more sharply defined by the precise mass spectrometry method than by enzyme-linked immunosorbent assay (mean difference of SD of residuals: A?40, -7.42 pM; P?<?.001; A?42, -3.72 pM; P?<?.001). Amyloid deposition diminished day/night amplitude and linear increase of A?42 but not of A?40. Increased age diminished day/night amplitude of both A?40 and A?42. After controlling for amyloid deposition, amplitude of A?40 was positively associated with production rates (r?=?0.42; P?<?.001), while the linear rise was associated with turnover rates (r?=?0.28; P?<?.05). The amplitude and linear rise of A?42 were both associated with turnover (r?=?-0.38; P?<?.001) and production (r?=?0.238; P?<?.05) rates. Conclusions and Relevance:Amyloid deposition is associated with premature loss of normal A?42 day/night patterns in older adults, suggesting the previously reported effects of age and amyloid on A?42 amplitude at least partially affect each other. Production and turnover rates suggest that day/night A? patterns are modulated by both production and clearance mechanisms active in sleep-wake cycles and that amyloid deposition may impair normal circadian patterns. These findings may be important for the designs of future secondary prevention trials for Alzheimer disease.

Dataset Information

Characterization of the beta amyloid precursor protein-like gene in the central nervous system of the crab Chasmagnathus. Expression during memory consolidation.

Publications

Characterization of the beta amyloid precursor protein-like gene in the central nervous system of the crab Chasmagnathus. Expression during memory consolidation.

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