title: Neonatal exposure to the cyanobacterial toxin BMAA induces changes in protein expression and neurodegeneration in adult hippocampus.
abstract: The cyanobacterial toxin β-N-methylamino-L-alanine (BMAA) has been proposed to contribute to neurodegenerative disease. We have previously reported a selective uptake of BMAA in the mouse neonatal hippocampus and that exposure during the neonatal period causes learning and memory impairments in adult rats. The aim of this study was to characterize effects in the brain of 6-month-old rats treated neonatally (postnatal days 9-10) with the glutamatergic BMAA. Protein changes were examined using the novel technique Matrix-Assisted Laser Desorption Ionization (MALDI) imaging mass spectrometry (IMS) for direct imaging of proteins in brain cryosections, and histological changes were examined using immunohistochemistry and histopathology. The results showed long-term changes including a decreased expression of proteins involved in energy metabolism and intracellular signaling in the adult hippocampus at a dose (150 mg/kg) that gave no histopathological lesions in this brain region. Developmental exposure to a higher dose (460 mg/kg) also induced changes in the expression of S100β, histones, calcium- and calmodulin-binding proteins, and guanine nucleotide-binding proteins. At this dose, severe lesions in the adult hippocampus including neuronal degeneration, cell loss, calcium deposits, and astrogliosis were evident. The data demonstrate subtle, sometimes dose-dependent, but permanent effects of a lower neonatal dose of BMAA in the adult hippocampus suggesting that BMAA could potentially disturb many processes during the development. The detection of BMAA in seafood stresses the importance of evaluating the magnitude of human exposure to this neurotoxin.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, 75124 Uppsala, Sweden. oskar.karlsson@farmbio.uu.se
authors.forename: Oskar
authors.initials: O
authors.lastname: Karlsson
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Berg
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Lindström
authors.forename: Jörg
authors.initials: J
authors.lastname: Hanrieder
authors.forename: Gunnel
authors.initials: G
authors.lastname: Arnerup
authors.forename: Erika
authors.initials: E
authors.lastname: Roman
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.forename: Nils Gunnar
authors.initials: NG
authors.lastname: Lindquist
authors.forename: Eva B
authors.initials: EB
authors.lastname: Brittebo
authors.forename: Malin
authors.initials: M
authors.lastname: Andersson
mesh_terms: D000367:Age Factors; D000599:Amino Acids, Diamino / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001427:Bacterial Toxins / Q000633:toxicity*; D000087522:Cyanobacteria Toxins; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005506:Food Contamination; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008387:Marine Toxins / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors
chemical_list: D000599:Amino Acids, Diamino; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D009419:Nerve Tissue Proteins; C001824:beta-N-methylamino-L-alanine