Changes in the metabolic profile of human male postmortem frontal cortex and cerebrospinal fluid samples associated with heavy alcohol use

Olli Kärkkäinen, Marietta Kokla, Marko Lehtonen, Seppo Auriola, Mika Martiskainen, Jari Tiihonen, Pekka J. Karhunen, Kati Hanhineva, Eloise Kok

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Heavy alcohol use is one of the top causes of disease and death in the world. The brain is a key organ affected by heavy alcohol use. Here, our aim was to measure changes caused by heavy alcohol use in the human brain metabolic profile. We analyzed human postmortem frontal cortex and cerebrospinal fluid (CSF) samples from males with a history of heavy alcohol use (n = 74) and controls (n = 74) of the Tampere Sudden Death Series cohort. We used a nontargeted liquid chromatography mass spectrometry-based metabolomics method. We observed differences between the study groups in the metabolite levels of both frontal cortex and CSF samples, for example, in amino acids and derivatives, and acylcarnitines. There were more significant alterations in the metabolites of frontal cortex than in CSF. In the frontal cortex, significant alterations were seen in the levels of neurotransmitters (e.g., decreased levels of GABA and acetylcholine), acylcarnitines (e.g., increased levels of acylcarnitine 4:0), and in some metabolites associated with alcohol metabolizing enzymes (e.g., increased levels of 2-piperidone). Some of these changes were also significant in the CSF samples (e.g., elevated 2-piperidone levels). Overall, these results show the metabolites associated with neurotransmitters, energy metabolism and alcohol metabolism, were altered in human postmortem frontal cortex and CSF samples of persons with a history of heavy alcohol use.

Original languageEnglish
JournalADDICTION BIOLOGY
DOIs
Publication statusE-pub ahead of print - 21 Mar 2021
Publication typeA1 Journal article-refereed

Keywords

  • alcohol
  • alcoholism
  • brain
  • metabolomics
  • microbiota

Publication forum classification

  • Publication forum level 2

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

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