Neonatal exposure to the cyanobacterial toxin BMAA induces changes in protein expression and neurodegeneration in adult hippocampus.
Journal article, 2012
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.
Marine Toxins
toxicity
Amino Acids
Neurodegenerative Diseases
Animals
metabolism
pathology
etiology
Wistar
metabolism
Mass
Time Factors
Rats
Energy Metabolism
Newborn
Drug
Hippocampus
Dose-Response Relationship
Risk Assessment
Diamino
drug effects
metabolism
Food Contamination
Rats
chemically induced
toxicity
Neurotoxicity Syndromes
Nerve Tissue Proteins
Bacterial Toxins
drug effects
Matrix-Assisted Laser Desorption-Ionization
drug effects
Spectrometry
pathology
Signal Transduction
Animals
toxicity
pathology
Immunohistochemistry
Age Factors
metabolism
Author
Oskar Karlsson
Anna-Lena Berg
Anna-Karin Lindström
Jörg Hanrieder
Gunnel Arnerup
Erika Roman
Jonas Bergquist
Nils Gunnar Lindquist
Eva B Brittebo
Malin Andersson
Toxicological Sciences
1096-6080 (ISSN) 1096-0929 (eISSN)
Vol. 130 2 391-404Subject Categories
Basic Medicine
Neurosciences
Pharmacology and Toxicology
DOI
10.1093/toxsci/kfs241
PubMed
22872059