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Title: Distribution of Alox15 in the Rat Brain and Its Role in Prefrontal Cortical Resolvin D1 Formation and Spatial Working Memory
Authors: Shalini, S.-M
Ho, C.F.-Y
Ng, Y.-K 
Tong, J.-X 
Ong, E.-S
Herr, D.R 
Dawe, G.S 
Ong, W.-Y 
Keywords: arachidonate 15 lipoxygenase
carrier proteins and binding proteins
resolvin D1
unclassified drug
arachidonate 15 lipoxygenase
docosahexaenoic acid
resolvin D1
animal experiment
animal tissue
auditory cortex
cochlear nucleus
controlled study
enzyme inhibition
immunoelectron microscopy
liquid chromatography
long term potentiation
mass spectrometry
motor cortex
olfactory bulb
prefrontal cortex
protein expression
protein localization
real time polymerase chain reaction
reverse transcription polymerase chain reaction
secondary somatosensory cortex
spatial memory
spinal cord dorsal horn
spinal trigeminal nucleus
T-maze test
Western blotting
working memory
prefrontal cortex
short term memory
spatial memory
Wistar rat
Arachidonate 15-Lipoxygenase
Docosahexaenoic Acids
Memory, Short-Term
Prefrontal Cortex
Rats, Wistar
Spatial Memory
Issue Date: 2018
Publisher: Humana Press Inc.
Citation: Shalini, S.-M, Ho, C.F.-Y, Ng, Y.-K, Tong, J.-X, Ong, E.-S, Herr, D.R, Dawe, G.S, Ong, W.-Y (2018). Distribution of Alox15 in the Rat Brain and Its Role in Prefrontal Cortical Resolvin D1 Formation and Spatial Working Memory. Molecular Neurobiology 55 (2) : 1537-1550. ScholarBank@NUS Repository.
Abstract: Docosahexaenoic acid (DHA) is enriched in membrane phospholipids of the central nervous system (CNS) and has a role in aging and neuropsychiatric disorders. DHA is metabolized by the enzyme Alox15 to 17S-hydroxy-DHA, which is then converted to 7S-hydroperoxy,17S-hydroxy-DHA by a 5-lipoxygenase, and thence via epoxy intermediates to the anti-inflammatory molecule, resolvin D1 (RvD1 or 7S,8R,17S-trihydroxy-docosa-Z,9E,11E,13Z,15E,19Z-hexaenoic acid). In this study, we investigated the distribution and function of Alox15 in the CNS. RT-PCR of the CNS showed that the prefrontal cortex exhibits the highest Alox15 mRNA expression level, followed by the parietal association cortex and secondary auditory cortex, olfactory bulb, motor and somatosensory cortices, and the hippocampus. Western blot analysis was consistent with RT-PCR data, in that the prefrontal cortex, cerebral cortex, hippocampus, and olfactory bulb had high Alox15 protein expression. Immunohistochemistry showed moderate staining in the olfactory bulb, cerebral cortex, septum, striatum, cerebellar cortex, cochlear nuclei, spinal trigeminal nucleus, and dorsal horn of the spinal cord. Immuno-electron microscopy showed localization of Alox15 in dendrites, in the prefrontal cortex. Liquid chromatography mass spectrometry analysis showed significant decrease in resolvin D1 levels in the prefrontal cortex after inhibition or antisense knockdown of Alox15. Alox15 inhibition or antisense knockdown in the prefrontal cortex also blocked long-term potentiation of the hippocampo-prefrontal cortex pathway and increased errors in alternation, in the T-maze test. They indicate that Alox15 processing of DHA contributes to production of resolvin D1 and LTP at hippocampo-prefrontal cortical synapses and associated spatial working memory performance. Together, results provide evidence for a key role of anti-inflammatory molecules generated by Alox15 and DHA, such as resolvin D1, in memory. They suggest that neuroinflammatory brain disorders and chronic neurodegeneration may ‘drain’ anti-inflammatory molecules that are necessary for normal neuronal signaling, and compromise cognition. © 2017, The Author(s).
Source Title: Molecular Neurobiology
ISSN: 0893-7648
DOI: 10.1007/s12035-017-0413-x
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