TY - JOUR
T1 - Brain proteomic atlas of alcohol use disorder in adult males
AU - Teng, Pang ning
AU - Barakat, Waleed
AU - Tran, Sophie M.
AU - Tran, Zoe M.
AU - Bateman, Nicholas W.
AU - Conrads, Kelly A.
AU - Wilson, Katlin N.
AU - Oliver, Julie
AU - Gist, Glenn
AU - Hood, Brian L.
AU - Zhou, Ming
AU - Maxwell, G. Larry
AU - Leggio, Lorenzo
AU - Conrads, Thomas P.
AU - Lee, Mary R.
N1 - Funding Information:
The authors thank Salma Eltahir, Marshé Edwards, Sakiyah TaQee, Jeremy Loffredo, Persus Akowuah, Dave Mitchell, Sasha Makohon-Moore and Tamara Abulez for their contribution to sample preparation, processing, and data analysis. The authors would also like to thank Ms. Donna Sheedy, Dr. Greg Sutherland, and Dr. Jillian Kril from the New South Wales Tissue Resource Centre (NSWBTRC) at the University of Sydney, Australia, for providing the human postmortem brain tissue for this project.
Funding Information:
This study was supported in part by NIH intramural funding ZIA-DA-000635 (Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section—PI: LL), jointly supported by the NIDA Intramural Research Program and the NIAAA Division of Intramural Clinical and Biological Research (MRL, LL). Brain tissues were received from the New South Wales Brain Tissue Resource Centre (NSWBTRC) at the University of Sydney, which is supported by NIAAA under Award Number R28AA012725 and Neuroscience Research Australia. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - Alcohol use disorder (AUD) affects transcriptomic, epigenetic and proteomic expression in several organs, including the brain. There has not been a comprehensive analysis of altered protein abundance focusing on the multiple brain regions that undergo neuroadaptations occurring in AUD. We performed a quantitative proteomic analysis using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of human postmortem tissue from brain regions that play key roles in the development and maintenance of AUD, the amygdala (AMG), hippocampus (HIPP), hypothalamus (HYP), nucleus accumbens (NAc), prefrontal cortex (PFC) and ventral tegmental area (VTA). Brain tissues were from adult males with AUD (n = 11) and matched controls (n = 16). Across the two groups, there were >6000 proteins quantified with differential protein abundance in AUD compared to controls in each of the six brain regions. The region with the greatest number of differentially expressed proteins was the AMG, followed by the HYP. Pathways associated with differentially expressed proteins between groups (fold change > 1.5 and LIMMA p < 0.01) were analyzed by Ingenuity Pathway Analysis (IPA). In the AMG, adrenergic, opioid, oxytocin, GABA receptor and cytokine pathways were among the most enriched. In the HYP, dopaminergic signaling pathways were the most enriched. Proteins with differential abundance in AUD highlight potential therapeutic targets such as oxytocin, CSNK1D (PF-670462), GABAB receptor and opioid receptors and may lead to the identification of other potential targets. These results improve our understanding of the molecular alterations of AUD across brain regions that are associated with the development and maintenance of AUD. Proteomic data from this study is publicly available at www.lmdomics.org/AUDBrainProteomeAtlas/ .
AB - Alcohol use disorder (AUD) affects transcriptomic, epigenetic and proteomic expression in several organs, including the brain. There has not been a comprehensive analysis of altered protein abundance focusing on the multiple brain regions that undergo neuroadaptations occurring in AUD. We performed a quantitative proteomic analysis using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of human postmortem tissue from brain regions that play key roles in the development and maintenance of AUD, the amygdala (AMG), hippocampus (HIPP), hypothalamus (HYP), nucleus accumbens (NAc), prefrontal cortex (PFC) and ventral tegmental area (VTA). Brain tissues were from adult males with AUD (n = 11) and matched controls (n = 16). Across the two groups, there were >6000 proteins quantified with differential protein abundance in AUD compared to controls in each of the six brain regions. The region with the greatest number of differentially expressed proteins was the AMG, followed by the HYP. Pathways associated with differentially expressed proteins between groups (fold change > 1.5 and LIMMA p < 0.01) were analyzed by Ingenuity Pathway Analysis (IPA). In the AMG, adrenergic, opioid, oxytocin, GABA receptor and cytokine pathways were among the most enriched. In the HYP, dopaminergic signaling pathways were the most enriched. Proteins with differential abundance in AUD highlight potential therapeutic targets such as oxytocin, CSNK1D (PF-670462), GABAB receptor and opioid receptors and may lead to the identification of other potential targets. These results improve our understanding of the molecular alterations of AUD across brain regions that are associated with the development and maintenance of AUD. Proteomic data from this study is publicly available at www.lmdomics.org/AUDBrainProteomeAtlas/ .
UR - http://www.scopus.com/inward/record.url?scp=85174302116&partnerID=8YFLogxK
U2 - 10.1038/s41398-023-02605-0
DO - 10.1038/s41398-023-02605-0
M3 - Article
C2 - 37833300
AN - SCOPUS:85174302116
SN - 2158-3188
VL - 13
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 318
ER -