TY - JOUR
T1 - G-protein signaling, lipid rafts and the possible sites of action for the antidepressant effects of n-3 polyunsaturated fatty acids.
AU - Czysz, Andrew H.
AU - Rasenick, Mark M.
PY - 2013/6
Y1 - 2013/6
N2 - Dietary fish oil, a source of polyunsaturated fatty acids (n-3 PUFA), has become increasingly popular for antidepressant therapy, in part because about half of patients treated with conventional antidepressants either fail to remit or discontinue therapy due to side effects. The inception of n-3 PUFA as a putative depression therapeutic may have stemmed from reports suggesting that dietary n-3 PUFA deficiency is linked to both altered membrane PUFA content as well as clinical depression. Several studies have examined n-3 PUFA treatment in depression, either singly or in combination with conventional antidepressant drugs. While results have been encouraging, fish oil treatment remains controversial. At least some of the reason for this is the lack of a defined site of action for n-3 PUFA that would be consistent with an antidepressant effect. This review will address this issue. While it is possible, even likely, that n-3 PUFA have multiple sites of action, this chapter will focus on sites at which n-3 PUFA modify G protein signaling and how those sites relate to both depression and antidepressant action. Much of the focus herein will be on specialized membrane domains (lipid rafts) and the effects that agents modifying those rafts have on elements of G protein signaling cascades. The relevance of specific alterations of G protein signaling for both depression and antidepressant action will be discussed, as will the ability for n-3 PUFA to act either as an antidepressant or in concert with conventional antidepressants.
AB - Dietary fish oil, a source of polyunsaturated fatty acids (n-3 PUFA), has become increasingly popular for antidepressant therapy, in part because about half of patients treated with conventional antidepressants either fail to remit or discontinue therapy due to side effects. The inception of n-3 PUFA as a putative depression therapeutic may have stemmed from reports suggesting that dietary n-3 PUFA deficiency is linked to both altered membrane PUFA content as well as clinical depression. Several studies have examined n-3 PUFA treatment in depression, either singly or in combination with conventional antidepressant drugs. While results have been encouraging, fish oil treatment remains controversial. At least some of the reason for this is the lack of a defined site of action for n-3 PUFA that would be consistent with an antidepressant effect. This review will address this issue. While it is possible, even likely, that n-3 PUFA have multiple sites of action, this chapter will focus on sites at which n-3 PUFA modify G protein signaling and how those sites relate to both depression and antidepressant action. Much of the focus herein will be on specialized membrane domains (lipid rafts) and the effects that agents modifying those rafts have on elements of G protein signaling cascades. The relevance of specific alterations of G protein signaling for both depression and antidepressant action will be discussed, as will the ability for n-3 PUFA to act either as an antidepressant or in concert with conventional antidepressants.
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U2 - 10.2174/1871527311312040005
DO - 10.2174/1871527311312040005
M3 - Review article
C2 - 23574156
AN - SCOPUS:84894361065
SN - 1871-5273
VL - 12
SP - 466
EP - 473
JO - CNS & neurological disorders drug targets
JF - CNS & neurological disorders drug targets
IS - 4
ER -