Genetic alterations or early environmental challenges typically lead to many neurobiological changes. While it is certainly possible to predict some of these, the complexity of the brain and the neuronal connectivity make it necessary to use special techniques that go beyond the standard “hypothesis-driven” approach. Over the last decades the research field has developed numerous so-called “hypothesis-free” techniques, such as genome wide association studies, RNA sequencing and proteomics. Together with our collaborators Drs Rob Keijzers and Bill Jordan, we are using two of these techniques: Maldi and metabolomics.
Maldi (Matrix Assisted Laser Desorption/Ionization) is a technique that allows the detection and distribution of many different compounds in biological tissues. The idea is that a brain section is coated with a specific matrix (a chemical coating) and subsequently exposed to a laser beam. This laser created heat which vaporises the top layer of both the matrix and the brain section. The resulting ions can then be detected with mass spectroscopy. The great benefit of Maldi for neuroscience is that the laser can be targeted to a very small region (in the order to 50 micrometers). By moving the laser across a brain slice, we can get a detailed map of the distribution of different neurobiological compounds. By adjusting the matrix, we can assess many different components of the brain (neurotransmitters, lipids etc).
Metabolomics refers to the “systematic study of the unique chemical fingerprints that specific cellular processes leave behind”. As such it can be considered the final consequence of the genomics -> transcriptomics -> proteomics -> metabolomics process. There are several different methods that allow us to identify the metabolome of a biological sample (such as brain region or blood plasma), including mass spectroscopy, gas chromatography and nuclear magnetic resonance. Each of these methods have their own advantages and disadvantages in terms of ease of sample preparation, sensitivity and data interpretation. We therefore aim to use and compare all three detection methods while assessing the metabolome changes seen in SERT knock-out rats and in rats expose to maternal immune activation.
This project is in part supported by a grant from “Research for Life” (formerly the Wellington Medical Research Foundation).