Neuroscience and accelerator mass spectrometry

Abstract

Accelerator mass spectrometry (AMS) is a mass spectrometric method for quantifying rare isotopes. It has had a great impact in geochronology and archaeology and is now being applied in biomedicine. AMS measures radioisotopes such as 3 H, 14 C, 26 Al, 36 Cl and 41 Ca, with zepto-or attomole sensitivity and high precision and throughput, allowing safe human pharmacokinetic studies involving microgram doses, agents having low bioavailability or toxicology studies where administered doses must be kept low (<1 µg kg −1 ). It is used to study long-term pharmacokinetics, to identify biomolecular interactions, to determine chronic and low-dose effects or molecular targets of neurotoxic substances, to quantify transport across the blood-brain barrier and to resolve molecular turnover rates in the human brain on the time-scale of decades. We review here how AMS is applied in neurotoxicology and neuroscience.

Atomic spectrometry update. Atomic mass spectrometry

“…In the last decade, AMS has emerged as a sensitive tool for bioanalytical tracing. Reviews on the use of AMS in neuroscience 8 and phytochemical research 9 highlighted the possibility of quantifying isotopes at the 1 in 10 15 level. This corresponded to zepto-to attomoles of isotopically labelled compounds in mg to mg amounts of sample.…”

Quantifying exploratory low dose compounds in humans with AMS

“…)[72]. The pesticide exposures significantly increased the amount of DFP, a miotic pharmaceutical often used as a research analog of organophosphate pesticides and nerve agents, bound to the cholinesterase in the brain, suggesting a possible link between cholinergic pesticide exposure and increased susceptibility to very low amounts of nerve agents among certain troops after destruction of nerve gas depots [73-74]. The study further demonstrated that daily doses of the protective transient cholinesterase inhibitor, pyridostigmine bromide, sub-chronically dosed at 50 μg/kg prior to 14 C-DFP administration, produced a significant 15% decrease in brain-bound DFP.…”

Accelerator mass spectrometry

“…The cells in the cortex of the adult human brain have been investigated, and it was found that while non-neuronal cells are replaced, occipital neurons are as old as the individual (Spalding et al, 2005;Bhardwaj et al, 2006). The AMS measurements for these investigations (Palmblad et al, 2005) were performed at the Lawrence Livermore National Laboratory. 14 C levels from samples containing as little as 30 mg carbon were analyzed (corresponding to genomic DNA from 15 million cells), thus taking advantage of the full potential of the AMS method.…”