Molecular neurobiology
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Molecular neurobiology · Aug 2014
Distribution of secretory phospholipase A2 XIIA in the brain and its role in lipid metabolism and cognition.
Phospholipases A(2) (PLA(2)) catalyze the hydrolysis of membrane phospholipids to produce free fatty acids and lysophospholipids, which have important functions in cell signaling. The present study elucidated differential expression of PLA(2) isoforms in the rat cortex by quantitative reverse transcription PCR and demonstrated that sPLA(2)-XIIA had greater messenger RNA expression than iPLA(2)-VI or cPLA(2)-IVA in different brain regions, or compared to other sPLA(2) isoforms in the prefrontal cortex (PFC) and hippocampus. ⋯ Injection of antisense oligonucleotide to sPLA(2)-XIIA in the PFC and lipidomic analysis showed increase in phospholipid but decrease in lysophospholipid species consistent with decreased catalytic activity of the enzyme, changes in arachidonic acid release, and alterations in sphingolipids. sPLA(2)-XIIA knockdown also resulted in shorter latency timings in the passive avoidance test, and higher number of errors in the attention set-shifting task, indicating deficits in working memory and attention. Together, the results show an important role of sPLA(2)-XIIA in lipid metabolism, prefrontal cortical function, and cognition.
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Molecular neurobiology · Aug 2014
Neurorestorative targets of dietary long-chain omega-3 fatty acids in neurological injury.
Long-chain omega-3 polyunsaturated fatty acids (LC-O3PUFAs) exhibit therapeutic potential for the treatment and prevention of the neurological deficits associated with spinal cord injury (SCI). However, the mechanisms implicated in these protective responses remain unclear. The objective of the present functional metabolomics study was to identify and define the dominant metabolic pathways targeted by dietary LC-O3PUFAs. ⋯ Further, we found that dietary LC-O3PUFAs impacted the levels of neurotransmitters and the mitochondrial metabolism, as evidenced by significant increases in the levels of N-acetylglutamate (+43 %) and acetyl CoA levels (+27 %), respectively. Interestingly, this dietary intervention resulted in a global correction of the pro-oxidant metabolic profile that characterized the SCI-mediated sensorimotor dysfunction. In summary, the significant benefits of metabolic homeostasis and increased antioxidant defenses unlock important neurorestorative pathways of dietary LC-O3PUFAs against SCI.