| Title |
Intracellular fibril formation, calcification, and enrichment of chaperones, cytoskeletal, and intermediate filament proteins in the adult hippocampus CA1 following neonatal exposure to the nonprotein amino acid BMAA
|
|---|---|
| Published in |
Archives of Toxicology, May 2014
|
| DOI | 10.1007/s00204-014-1262-2 |
| Pubmed ID | |
| Authors |
Oskar Karlsson, Anna-Lena Berg, Jörg Hanrieder, Gunnel Arnerup, Anna-Karin Lindström, Eva B. Brittebo |
| Abstract |
The environmental neurotoxin β-N-methylamino-L-alanine (BMAA) has been implicated in the etiology of neurodegenerative disease, and recent studies indicate that BMAA can be misincorporated into proteins. BMAA is a developmental neurotoxicant that can induce long-term learning and memory deficits, as well as regionally restricted neuronal degeneration and mineralization in the hippocampal CA1. The aim of the study was to characterize long-term changes (2 weeks to 6 months) further in the brain of adult rats treated neonatally (postnatal days 9-10) with BMAA (460 mg/kg) using immunohistochemistry (IHC), transmission electron microscopy, and laser capture microdissection followed by LC-MS/MS for proteomic analysis. The histological examination demonstrated progressive neurodegenerative changes, astrogliosis, microglial activation, and calcification in the hippocampal CA1 3-6 months after exposure. The IHC showed an increased staining for α-synuclein and ubiquitin in the area. The ultrastructural examination revealed intracellular deposition of abundant bundles of closely packed parallel fibrils in neurons, axons, and astrocytes of the CA1. Proteomic analysis of the affected site demonstrated an enrichment of chaperones (e.g., clusterin, GRP-78), cytoskeletal and intermediate filament proteins, and proteins involved in the antioxidant defense system. Several of the most enriched proteins (plectin, glial fibrillar acidic protein, vimentin, Hsp 27, and ubiquitin) are known to form complex astrocytic inclusions, so-called Rosenthal fibers, in the neurodegenerative disorder Alexander disease. In addition, TDP-43 and the negative regulator of autophagy, GLIPR-2, were exclusively detected. The present study demonstrates that neonatal exposure to BMAA may offer a novel model for the study of hippocampal fibril formation in vivo. |
Mendeley readers
The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 2% |
| Unknown | 53 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 17% |
| Student > Master | 8 | 15% |
| Student > Doctoral Student | 8 | 15% |
| Student > Ph. D. Student | 8 | 15% |
| Student > Bachelor | 7 | 13% |
| Other | 7 | 13% |
| Unknown | 7 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 11 | 20% |
| Agricultural and Biological Sciences | 9 | 17% |
| Neuroscience | 7 | 13% |
| Medicine and Dentistry | 5 | 9% |
| Chemistry | 4 | 7% |
| Other | 10 | 19% |
| Unknown | 8 | 15% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 August 2020.
All research outputs
#7,453,479
of 22,786,691 outputs
Outputs from Archives of Toxicology
#958
of 2,635 outputs
Outputs of similar age
#74,041
of 227,453 outputs
Outputs of similar age from Archives of Toxicology
#11
of 35 outputs
Altmetric has tracked 22,786,691 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,635 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one is in the 30th percentile – i.e., 30% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 227,453 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.