Chronic ethanol consumption profoundly alters regional brain ceramide and sphingomyelin content in rodents.
Ceramides (CER) are involved in alcohol-induced neuroinflammation. In a mouse model of chronic alcohol exposure, 16 CER and 18 sphingomyelin (SM) concentrations from whole brain lipid extracts were measured using electrospray mass spectrometry. All 18 CER concentrations in alcohol exposed adults increased significantly (range: 25-607%); in juveniles, 6 CER decreased (range: -9 to -37%). In contrast, only three SM decreased in adult and one increased significantly in juvenile. Next, regional identification at 50 μm spatial resolution from coronal sections was obtained with matrix implanted laser desorption/ionization mass spectrometry imaging (MILDI-MSI) by implanting silver nanoparticulate matrices followed by focused laser desorption. Most of the CER and SM quantified in whole brain extracts were detected in MILDI images. Coronal sections from three brain levels show qualitative regional changes in CER-SM ion intensities, as a function of group and brain region, in cortex, striatum, accumbens, habenula, and hippocampus. Highly correlated changes in certain white matter CER-SM pairs occur in regions across all groups, including the hippocampus and the lateral (but not medial) cerebellar cortex of adult mice. Our data provide the first microscale MS evidence of regional lipid intensity variations induced by alcohol.
Structural Biology Unit, NIDA IRP, NIH , Baltimore, Maryland 21224, United States.
Aurelie
A
Roux
Ludovic
L
Muller
Shelley N
SN
Jackson
Katherine
K
Baldwin
Virginia
V
Womack
John G
JG
Pagiazitis
Joseph R
JR
O'Rourke
Panayotis K
PK
Thanos
Carey
C
Balaban
J Albert
JA
Schultz
Nora D
ND
Volkow
Amina S
AS
Woods
D000428:Alcohol Drinking / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D002518:Ceramides / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D053768:Metal Nanoparticles; D008810:Mice, Inbred C57BL; D018030:Silver Compounds; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013109:Sphingomyelins / Q000378:metabolism*; D066127:White Matter / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
D002492:Central Nervous System Depressants; D002518:Ceramides; D018030:Silver Compounds; D013109:Sphingomyelins; D000431:Ethanol
Ceramide; alcohol; lipids; mass spectrometry imaging; matrix implanted laser desorption ionization; matrix-assisted laser desorption ionization; silver nanoparticles; sphingomyelin