Remodeling of brain lipidome in methamphetamine-sensitized mice

Toxicol Lett. 2017 Sep 5:279:67-76. doi: 10.1016/j.toxlet.2017.07.214. Epub 2017 Jul 6.

Abstract

Lipids are predominant components of the brain and key regulators for neural structure and function. The effect of methamphetamine (METH) on behavior, cognition as well as memory has been intensively investigated; however, the impact of METH on brain lipid profiles is largely unknown. Here, we used a global lipidomic approach to investigate brain lipidome of METH-sensitized mice. We found that repeated METH significantly modified the lipidome in the hippocampus, prefrontal cortex (PFC) and striatum. Interestingly, nucleus accumbens showed no obvious alteration in lipidomic profiling. Phospholipid and sphingolipid metabolisms were profoundly modified in the hippocampus of METH-sensitized mice, exhibiting increased phosphatidic acid and ether phosphatidylcholine but decreased lysophosphatidylethanolamine, lactosylceramide and triglycerides. The fatty acyl length of phospholipids and diacylglycerol longer than 40 carbon were clearly decreased in the hippocampus, and that 36 carbon was decreased in the PFC. These results indicate METH can profoundly affect the metabolism of phospholipids, sphingolipids and glycerolipids in the brain. Our findings reveal a link between remodeled brain lipidome and neurobehavior induced by METH.

Keywords: Locomotor activity; Methamphetamine; Phospholipid; Sphingolipid.

MeSH terms

  • Animals
  • Basal Ganglia / drug effects*
  • Basal Ganglia / metabolism
  • Behavior, Animal / drug effects
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / toxicity*
  • Fatty Acids / metabolism
  • Glycerides / metabolism
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Lipid Metabolism / drug effects*
  • Male
  • Methamphetamine / administration & dosage
  • Methamphetamine / toxicity*
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Phospholipids / metabolism
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Sphingolipids / metabolism
  • Time Factors

Substances

  • Central Nervous System Stimulants
  • Fatty Acids
  • Glycerides
  • Phospholipids
  • Sphingolipids
  • Methamphetamine