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

作者：Karlsson Oskar^*; Berg Anna Lena; Lindstrom Anna Karin; Hanrieder Jorg; Arnerup Gunnel; Roman Erika; Bergquist Jonas; Lindquist Nils Gunnar; Brittebo Eva B; Andersson Malin

来源：Toxicological Sciences, 2012, 130(2): 391-404.

DOI：10.1093/toxsci/kfs241

• ALS/PDC
• alpha-synuclein
• neuronal calcification
• MALDI imaging mass spectrometry
• proteomics
• hippocampus
• CA1

The cyanobacterial toxin -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 910) 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 S100, 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.

• 出版日期2012-12