Distinctive effects of arachidonic acid and docosahexaenoic acid on neural stem /progenitor cells

Abstract

Arachidonic acid (ARA) and docosahexaenoic acid (DHA), which are the dominant polyunsaturated fatty acids in the brain, have crucial roles in brain development and function. Recent studies have shown that ARA and DHA promote postnatal neurogenesis. However, the direct effects of ARA on neural stem ⁄ progenitor cells (NSPCs) and the effects of ARA and DHA on NSPCs at the neurogenic and subsequent gliogenic stages are still unknown. Here, we analyzed the effects of ARA and DHA on neurogenesis, specifically maintenance and differentiation, using neurosphere assays. We confirmed that primary neurospheres are neurogenic NSPCs and that tertiary neurospheres are gliogenic NSPCs. Regarding the effects of ARA and DHA on neurogenic NSPCs, ARA and DHA increased the number of neurospheres, whereas neither ARA nor DHA had a detectable effect on NSPCs in the differentiation condition. In gliogenic NSPCs, DHA increased the number of neurospheres, whereas ARA had no such effect. In contrast, ARA increased the number of astrocytes, whereas DHA increased the number of neurons in the differentiation condition. These results suggest that ARA promotes the maintenance of neurogenic NSPCs and might induce the glial differentiation of gliogenic NSPCs and that DHA promotes the maintenance of both neurogenic and gliogenic NSPCs and might lead to the neuronal differentiation of gliogenic NSPCs.

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

“…Furthermore, the initial reports of cell viability assays showed cells were most viable when DHA was added at the lowest dose (0.1 µM) (Katakura et al, 2009). There are also differences in methodologies used, as in these other studies the fatty acids were dissolved in media containing 1.0% fattyacid free bovine serum albumin (Katakura et al, 2009;Kawakita et al, 2006), whereas in the present study DHA was dissolved in ethanol and then diluted into the media.. DHA inhibited NSC proliferation consistent with previous studies Katakura et al, 2009); however, others have reported DHA enhances NSC proliferation (Sakayori et al, 2011). Sakoyori and co-workers suggested that the difference in effects on proliferation was the due to the lower DHA concentration promoting the maintenance of gliogenic NSCs.…”

“…Since this was the same dose as was used in our study it is more likely that this discrepancy is due to differences in the experimental conditions. In our study we collected NSC from ED16 fetal mice cortices, whereas Sakayori and co-workers used ED16.5 rats and Katakura and co-workers used ED 14.5 rats (Sakayori et al, 2011). There were also differences in the concentrations of heparin, FGF and EGF between studies, all of which are crucial determinants of NSC fate (Kelly et al, 2005).…”

“…Differences between the effects of AA and DHA on NSC fate have been observed previously (Sakayori et al, 2011). Thus it is possible that EPA is acting via endocannabinoid signalling pathways to promote proliferation, whereas DHA may 14 additionally be acting via alternative pathways, such as through conversion to the endocannabinoid-like metabolite, synaptamide, which has been shown to induce neuronal differentiation of NSCs via activation of protein kinase A (PKA)/cAMP response element binding protein (CREB) (Rashid et al, 2013).…”

Fatty acid binding proteins and the nervous system: Their impact on mental conditions

“…An in vivo study using juvenile rats, ARA increases proliferation of NSPCs in the hippocampus (Maekawa et al, 2009). In vitro neurosphere assays using cultured NSPCs derived from the embryonic rat cortical primordium, both DHA and ARA added into medium can induce increase in the number of neurospheres at the neurogenic stage (Sakayori et al, 2011). In the gliogenic stage when the neurospheres are passaged, DHA induces neuronal differentiation, whereas ARA causes astrocytic differentiation (Sakayori et al, 2011).…”

“…In vitro neurosphere assays using cultured NSPCs derived from the embryonic rat cortical primordium, both DHA and ARA added into medium can induce increase in the number of neurospheres at the neurogenic stage (Sakayori et al, 2011). In the gliogenic stage when the neurospheres are passaged, DHA induces neuronal differentiation, whereas ARA causes astrocytic differentiation (Sakayori et al, 2011). It would be interesting to know in future how Fabps are related with these differential roles of DHA and ARA in neurogenesis.…”