Journal Article

Neonatal Exposure to the Cyanobacterial Toxin BMAA Induces Changes in Protein Expression and Neurodegeneration in Adult Hippocampus

Oskar Karlsson, Anna-Lena Berg, Anna-Karin Lindström, Jörg Hanrieder, Gunnel Arnerup, Erika Roman, Jonas Bergquist, Nils Gunnar Lindquist, Eva B. Brittebo and Malin Andersson

in Toxicological Sciences

Volume 130, issue 2, pages 391-404
Published in print December 2012 | ISSN: 1096-6080
Published online August 2012 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfs241

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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 (150mg/kg) that gave no histopathological lesions in this brain region. Developmental exposure to a higher dose (460mg/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.

Keywords: ALS/PDC; α-synuclein; neuronal calcification; MALDI imaging mass spectrometry; proteomics; hippocampus; CA1

Journal Article.  8298 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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