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Non-targeted profiling of lipids during kainate-induced neuronal injury

Xue Li Guan^,1, Xin He^,1, Wei-Yi Ong^,2, Wee Kiang Yeo, Guanghou Shui and Markus R. Wenk^,*,2

Departments of
Biochemistry,

^* Biological Sciences and

Anatomy, The Yong Loo Lin School of Medicine, National University of Singapore, Singapore

²Correspondence: M.R.W., Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Dr., Block MD7, Singapore. E-mail: bchmrw{at}nus.edu.sg; W-Y.O., Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Dr., Block MD10, Singapore. E-mail: antongwy{at}nus.edu.sg

Kainate is a glutamate analog that has been widely used in pharmacological studies of neuronal injury related to ischemic conditions and epilepsy. While altered lipid metabolism has been implicated in kainate action, no study has yet investigated the associated changes in lipid metabolites on a systems scale. Here we describe a mass spectrometry-based approach for profiling of lipid mixtures in a nontargeted fashion. Combined with tandem mass spectrometry, this method aims to identify lipids that are altered between two conditions, the kainate-treated and the control hippocampal tissues. In addition to reductions in major phospholipids with mainly polyunsaturated fatty acyl chains, we find elevated levels of ions that correspond to acylated forms of phosphatidylethanolamines and ceramides. Acylated phosphatidylethanolamines are neuroprotective lipids and precursors for anandamide, which signals via cannabinoid receptors. Quantitative analysis of ceramides shows that many molecular species with different acyl compositions are increased during kainate treatment. This increase is mainly restricted to neurons rather than other brain cells in the hippocampus as revealed by immunohistochemistry of brain slices.—Guan, X. L., He, X., Ong, W.-Y., Yeo, W. K., Shui, G., Wenk, M. R. Non-targeted profiling of lipids during kainite-induced neuronal injury.

Key Words: lipidomics • neurotoxicity • mass spectrometry • ceramide • N-acylated phosphatidylethanolamine

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