Neonatal exposure to the cyanobacterial toxin BMAA induces changes in protein expression and neurodegeneration in adult hippocampus.
Artikel i vetenskaplig tidskrift, 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

Författare

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. 130 391-404

Ämneskategorier

Medicinska grundvetenskaper

Neurovetenskaper

Farmakologi och toxikologi

DOI

10.1093/toxsci/kfs241

PubMed

22872059