Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/120415
Title: FUNCTION AND REGULATION OF CALCIUM-INDEPENDENT PHOSPHOLIPASE A2 IN THE ATTENUATION OF PAIN IN MICE
Authors: CHEW WEE SIONG
Keywords: antidepressant, pain, iPLA2, noradrenaline, SREBP-2, MAPK/ERK
Issue Date: 23-Jan-2015
Source: CHEW WEE SIONG (2015-01-23). FUNCTION AND REGULATION OF CALCIUM-INDEPENDENT PHOSPHOLIPASE A2 IN THE ATTENUATION OF PAIN IN MICE. ScholarBank@NUS Repository.
Abstract: Prefrontal cortical calcium-independent phospholipase A2 (iPLA2) was found to be important for the antidepressive effect of the antidepressant, maprotiline. We investigated the role of iPLA2 in the antinociceptive effect of maprotiline and examined the potential pathways in regulation of iPLA2 expression induction as well as the effects of antidepressant treatment on 15-lipoxygenase (15-LOX), an enzyme that metabolizes docosahexaenoic acid (DHA) to docosanoids such as resolvins. Our results showed that antinociception was abolished when prefrontal cortical iPLA2 was inhibited, suggesting a role of iPLA2 in maprotiline-induced antinociception. Subsequent studies on the possible pathways indicate that adrenergic receptor stimulation causes increased iPLA2 expression via MAPK/ERK and sterol regulatory element binding protein-2 (SREBP-2). Antidepressant treatment also increased 15-LOX expression possibly via adrenergic receptor activation. The increase in DHA and its metabolites may then contribute to the antidepressant-induced antinociception by facilitating dorsolateral prefrontal cortex activity to stimulate the PAG and descending pain inhibitory pathway.
URI: http://scholarbank.nus.edu.sg/handle/10635/120415
Appears in Collections:Ph.D Theses (Open)

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