TY - JOUR
T1 - Investigating the effects of a FAAH inhibitor in the laterodorsal tegmental nucleus using a new ex vivo mouse preparation
AU - Prabhala, Bala Krishna
AU - Chettri, Jiwan
AU - Irrinki, Nagalakshmi
AU - Garg, Abhroop
AU - Jersie-Christensen, Rosa
AU - Jenssen, Håvard
AU - Mojsoska, Biljana
AU - Soni, Neeraj
AU - Kohlmeier, Kristi A.
N1 - Funding Information:
We wish to acknowledge our lab technician Christel Ammitzböll Halberg for helping us with obtaining viable LDT sections. We also acknowledge Carsten Uhd Nielsen for the fruitful discussions.
Publisher Copyright:
© 2023 The Authors
PY - 2023/12
Y1 - 2023/12
N2 - As part of the brainstem reticular activating system, the laterodorsal tegmentum (LDT) is a central player in regulating sleep, arousal, and motivated behaviors including addiction. The neuronal lipids within the LDT that could regulate neuronal activity and LDT signaling are not fully characterized due, in part, to the complication of the presence of fatty acid amide hydrolases (FAAH). To determine the lipids in the LDT, mouse brain slices at different stages of brain development (16, 26 and 66 days) were exposed ex vivo to the FAAH inhibitor oleyl trifluoromethyl ketone (OTMK). Metabolomics and proteomic analyses were conducted on matched samples. Metabolomics analysis revealed differences between OTMK treated and untreated LDT. Furthermore, a distinct phenotype (proteomic profile) as a function of OTMK treatment was observed in LDT from adolescent (66 days) mice indicating an effect of treatment with OTMK at later stages of brain development. Our data indicate that this ex vivo preparation could facilitate screening of different FAAH inhibitors in mammalian tissues, and more importantly, this preparation should allow a deeper characterization of global mass spectrometry-based omics profiles within the LDT.
AB - As part of the brainstem reticular activating system, the laterodorsal tegmentum (LDT) is a central player in regulating sleep, arousal, and motivated behaviors including addiction. The neuronal lipids within the LDT that could regulate neuronal activity and LDT signaling are not fully characterized due, in part, to the complication of the presence of fatty acid amide hydrolases (FAAH). To determine the lipids in the LDT, mouse brain slices at different stages of brain development (16, 26 and 66 days) were exposed ex vivo to the FAAH inhibitor oleyl trifluoromethyl ketone (OTMK). Metabolomics and proteomic analyses were conducted on matched samples. Metabolomics analysis revealed differences between OTMK treated and untreated LDT. Furthermore, a distinct phenotype (proteomic profile) as a function of OTMK treatment was observed in LDT from adolescent (66 days) mice indicating an effect of treatment with OTMK at later stages of brain development. Our data indicate that this ex vivo preparation could facilitate screening of different FAAH inhibitors in mammalian tissues, and more importantly, this preparation should allow a deeper characterization of global mass spectrometry-based omics profiles within the LDT.
KW - ex vivo model
KW - FAAH
KW - FAAH inhibitors
KW - LDT
KW - Lipids
KW - Metabolomics
KW - Mouse
KW - Oleyl trifluoro methyl ketone
KW - Proteomics
U2 - 10.1016/j.ejmcr.2023.100111
DO - 10.1016/j.ejmcr.2023.100111
M3 - Journal article
AN - SCOPUS:85168974912
SN - 2772-4174
VL - 9
JO - European Journal of Medicinal Chemistry Reports
JF - European Journal of Medicinal Chemistry Reports
M1 - 100111
ER -