Investigating the effects of a FAAH inhibitor in the laterodorsal tegmental nucleus using a new ex vivo mouse preparation
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Investigating the effects of a FAAH inhibitor in the laterodorsal tegmental nucleus using a new ex vivo mouse preparation. / Prabhala, Bala Krishna; Chettri, Jiwan; Irrinki, Nagalakshmi; Garg, Abhroop; Jersie-Christensen, Rosa; Jenssen, Håvard; Mojsoska, Biljana; Soni, Neeraj; Kohlmeier, Kristi Anne.
In: European Journal of Medicinal Chemistry Reports, Vol. 9, 100111, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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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 Anne
PY - 2023
Y1 - 2023
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.
U2 - 10.1016/j.ejmcr.2023.100111
DO - 10.1016/j.ejmcr.2023.100111
M3 - Journal article
VL - 9
JO - European Journal of Medicinal Chemistry Reports
JF - European Journal of Medicinal Chemistry Reports
SN - 1768-3254
M1 - 100111
ER -
ID: 362803926