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: Oskar Karlsson, Anna-Lena Berg, Anna-Karin Lindström, Jörg Hanrieder, Gunnel Arnerup, Erika Roman, Jonas Bergquist, Nils Gunnar Lindquist, Eva B Brittebo, Malin Andersson
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 130 Issue 2 Pg. 391-404 (Dec 2012) ISSN: 1096-0929 [Electronic] United States
• PMID: 22872059 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids, Diamino
• Bacterial Toxins
• Cyanobacteria Toxins
• Marine Toxins
• Nerve Tissue Proteins
• beta-N-methylamino-L-alanine

Topics

• Age Factors
• Amino Acids, Diamino (toxicity)
• Animals
• Animals, Newborn
• Bacterial Toxins (toxicity)
• Cyanobacteria Toxins
• Dose-Response Relationship, Drug
• Energy Metabolism (drug effects)
• Food Contamination
• Hippocampus (drug effects, metabolism, pathology)
• Immunohistochemistry
• Marine Toxins (toxicity)
• Nerve Tissue Proteins (metabolism)
• Neurodegenerative Diseases (chemically induced, metabolism, pathology)
• Neurotoxicity Syndromes (etiology, metabolism, pathology)
• Rats
• Rats, Wistar
• Risk Assessment
• Signal Transduction (drug effects)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Time Factors