High Resolution Metabolite Imaging in the Hippocampus Following Neonatal Exposure to the Environmental Toxin BMAA Using ToF-SIMS
Artikel i vetenskaplig tidskrift, 2014

The environmental neurotoxin beta-N-methylamino-L-alanine (BMAA) is suggested to be linked with neurodegenerative disease. In a rat model, neonatal exposure to BMAA induced selective uptake in the hippocampus and caused cell loss, mineralization and astrogliosis as well as learning and memory impairments in adulthood. Moreover, neonatal exposure resulted in increased protein ubiquitination in the cornus ammonis 1 (CA1) region of the adult hippocampus indicating that BMAA may induce protein aggregation. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) based imaging is a powerful technology for spatial profiling of small molecular weight compounds in biological tissues with high chemical specificity and high spatial resolution. The aim of this study was to characterize neurochemical changes in the hippocampus of six month-old rats treated neonatally (postnatal days 9-10) with BMAA. Multivariate data analysis of whole section ToF-SIMS scans was performed to delineate anatomical regions of interest based on their chemical distribution pattern. Further analysis of spectral data obtained from the outlined anatomical regions, including CA1 and dentate gyms (DG) revealed BMAA-induced long-term changes. Increased levels of phospholipids and protein fragments in the histopathologically altered CA1 region as well as phosphate depletion in the DG were observed. Moreover, high resolution SIMS imaging revealed a specific localization of phosphatidylcholine lipids, protein signals and potassium in the histopathologically altered CA1 These findings demonstrate that ToF-SIMS based imaging is a powerful approach for probing biochemical changes in situ and might serve as promising technique for investigating neurotoxin-induced brain pathology.

ToF-

MASS-SPECTROMETRY

Biochemistry & Molecular Biology

METHYLAMINO-L-ALANINE

ASTROCYTES

Medicinal

DISEASE

MOTOR-NEURONS

HUMAN SPINAL-CORD

CYANOBACTERIAL NEUROTOXIN

AMINO-ACID

RATS

Imaging mass spectrometry

hippocampus

ALS/PDC

beta-N-methylamino-L-alanine (BMAA)

Neurosciences

AMYOTROPHIC-LATERAL-SCLEROSIS

Chemistry

Författare

Jörg Hanrieder

Chalmers, Kemi- och bioteknik, Analytisk kemi

Lorenz Gerber

Chalmers, Kemi- och bioteknik, Analytisk kemi

Åsa P Sandelius

Göteborgs universitet

Eva B. Brittebo

Uppsala universitet

Andrew Ewing

Göteborgs universitet

Chalmers, Kemi- och bioteknik, Analytisk kemi

Oskar Karlsson

Uppsala universitet

ACS Chemical Neuroscience

1948-7193 (ISSN)

Vol. 5 7 568-575

Ämneskategorier

Neurovetenskaper

Farmakologi och toxikologi

DOI

10.1021/cn500039b