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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 [Neuromolecular Med] 2012 Dec; Vol. 14 (4), pp. 349-61. Date of Electronic Publication: 2012 Jul 14. - Publication Year :
- 2012
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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 :
- Animals
Anxiety metabolism
Anxiety pathology
Ataxia metabolism
Ataxia pathology
Cerebral Cortex pathology
Dentate Gyrus pathology
Exploratory Behavior drug effects
Fatty Acids metabolism
Female
Gliosis chemically induced
Gliosis metabolism
Male
Maze Learning drug effects
Mice
Mice, Inbred C57BL
Nerve Tissue Proteins metabolism
Peroxisomes metabolism
Psychomotor Performance drug effects
Random Allocation
Rotarod Performance Test
Sensation Disorders metabolism
Sensation Disorders pathology
Stearoyl-CoA Desaturase metabolism
Anxiety chemically induced
Ataxia chemically induced
Brain Chemistry drug effects
Cerebral Cortex chemistry
DEET toxicity
Dentate Gyrus chemistry
Disease Models, Animal
Permethrin toxicity
Persian Gulf Syndrome metabolism
Phosphatidylcholines metabolism
Pyridostigmine Bromide toxicity
Sensation Disorders chemically induced
Sphingomyelins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1174
- Volume :
- 14
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neuromolecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 22798222
- Full Text :
- https://doi.org/10.1007/s12017-012-8192-z