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Lipidomic Profiling of Phosphocholine Containing Brain Lipids in Mice with Sensorimotor Deficits and Anxiety-Like Features After Exposure to Gulf War Agents
- Source :
- NeuroMolecular Medicine. 14:349-361
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- The central nervous system (CNS)-based symptoms of Gulf War Illness (GWI) include motor dysfunction, anxiety, and cognitive impairment. Gulf War (GW) agents, such as pyridostigmine bromide (PB), permethrin (PER), N,N-diethyl-meta-toluamide (DEET), and stress, are among the contributory factors to the pathobiology of GWI. This study characterizes disturbances in phosphocholine-containing lipids that accompany neurobehavioral and neuropathological features associated with GW agent exposure. Exposed mice received PB orally, dermal application of PER and DEET and restraint stress daily for 28 days, while controls received vehicle during this period. Neurobehavioral studies included the rotarod, open field, and Morris water maze tests. Histopathological assessments included glial fibrillary acid protein, CD45, and Nissl staining. Liquid chromatography/mass spectrometry with source collision-induced dissociation in negative and positive ionization scanning modes was performed to characterize brain phosphatidylcholine (PC) and sphingomyelin (SM). A significant increase in ether containing PC (ePC34:0, ePC36:2, and ePC36:1) or long-chain fatty acid-containing PC (38:1, 40:4, 40:2) was observed in exposed mice compared with controls. Among differentially expressed PCs, levels of those with monounsaturated fatty acids were more affected than those with saturated and polyunsaturated fatty acids. Sensorimotor deficits and anxiety, together with an increase in astrocytosis, were observed in exposed mice compared with controls. These lipid changes suggest that alterations in peroxisomal pathways and stearoyl-CoA desaturase activity accompany neurobehavioral and neuropathological changes after GW agent exposure and represent possible treatment targets for the CNS symptoms of GWI.
- Subjects :
- Male
Central nervous system
DEET
Morris water navigation task
Poison control
Nerve Tissue Proteins
Anxiety
Pharmacology
Rotarod performance test
Open field
Mice
Random Allocation
Cellular and Molecular Neuroscience
symbols.namesake
Lipidomics
Peroxisomes
medicine
Animals
Persian Gulf Syndrome
Gliosis
Maze Learning
Permethrin
Brain Chemistry
Cerebral Cortex
chemistry.chemical_classification
business.industry
Fatty Acids
Sphingomyelins
Mice, Inbred C57BL
Disease Models, Animal
medicine.anatomical_structure
Neurology
chemistry
Rotarod Performance Test
Dentate Gyrus
Sensation Disorders
Exploratory Behavior
Phosphatidylcholines
Nissl body
symbols
Molecular Medicine
Ataxia
Female
business
Psychomotor Performance
Stearoyl-CoA Desaturase
Pyridostigmine Bromide
Polyunsaturated fatty acid
Subjects
Details
- ISSN :
- 15591174 and 15351084
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- NeuroMolecular Medicine
- Accession number :
- edsair.doi.dedup.....e67883a1ac55440fb2872d7e284932c8