PMID- 24779349 OWN - NLM STAT- MEDLINE DCOM- 20150310 LR - 20240321 IS - 1948-7193 (Electronic) IS - 1948-7193 (Print) IS - 1948-7193 (Linking) VI - 5 IP - 7 DP - 2014 Jul 16 TI - High resolution metabolite imaging in the hippocampus following neonatal exposure to the environmental toxin BMAA using ToF-SIMS. PG - 568-75 LID - 10.1021/cn500039b [doi] AB - 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 gyrus (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. FAU - Hanrieder, Jorg AU - Hanrieder J AD - National Center for Imaging Mass Spectrometry, University of Gothenburg and Chalmers University of Technology, SE-412 96 Gothenburg, Sweden. FAU - Gerber, Lorenz AU - Gerber L FAU - Persson Sandelius, Asa AU - Persson Sandelius A FAU - Brittebo, Eva B AU - Brittebo EB FAU - Ewing, Andrew G AU - Ewing AG FAU - Karlsson, Oskar AU - Karlsson O LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140509 PL - United States TA - ACS Chem Neurosci JT - ACS chemical neuroscience JID - 101525337 RN - 0 (Amino Acids, Diamino) RN - 0 (Cyanobacteria Toxins) RN - 0 (Hazardous Substances) RN - 108SA6URTV (beta-N-methylamino-L-alanine) SB - IM MH - Amino Acids, Diamino/*toxicity MH - Animals MH - Animals, Newborn MH - Brain Diseases/*chemically induced/*physiopathology MH - Cyanobacteria Toxins MH - Disease Models, Animal MH - Gliosis/chemically induced/physiopathology MH - Hazardous Substances MH - Hippocampus/growth & development/*physiopathology MH - Immunohistochemistry MH - Male MH - Mass Spectrometry/*methods MH - Multivariate Analysis MH - Rats, Wistar MH - Signal Processing, Computer-Assisted PMC - PMC4102959 EDAT- 2014/05/02 06:00 MHDA- 2015/03/11 06:00 PMCR- 2015/07/16 CRDT- 2014/05/01 06:00 PHST- 2014/05/01 06:00 [entrez] PHST- 2014/05/02 06:00 [pubmed] PHST- 2015/03/11 06:00 [medline] PHST- 2015/07/16 00:00 [pmc-release] AID - 10.1021/cn500039b [doi] PST - ppublish SO - ACS Chem Neurosci. 2014 Jul 16;5(7):568-75. doi: 10.1021/cn500039b. Epub 2014 May 9.