<i>N</i>‐docosahexaenoylethanolamine is a potent neurogenic factor for neural stem cell differentiation

Rashid, Mohammad A.; Katakura, Masanori; Kharebava, Giorgi; Kevala, Karl; Kim, Hee‐Yong

doi:10.1111/jnc.12255

Cited by 86 publications

(81 citation statements)

References 53 publications

(122 reference statements)

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“…While GFAP/Gp120 Tg mice exhibited impaired neurogenesis and a decrease in cells with proliferating cell nuclear antigen (PCNA), administration of AM1241 to GFAP/Gp120 Tg mice resulted in enhanced in vivo neurogenesis in the hippocampus. An endogenous metabolite of docosahexaenoic acid and its derivatives (N-docosahexaenoylethanolamine and N-docosahexaenoylethanolamide) were shown to stimulate neurite growth, synaptogenesis, glutamatergic synaptic activity and neuronal differentiation of neural cells in hippocampal neurons [50,51]. Results of subsequent studies also confirmed the influence of the endocannabinoid system on neural progenitor cells (NCPs) regulation.…”

Section: Neurogenesis and Cannabinoidssupporting

confidence: 61%

Endocannabinoid system and cannabinoids in neurogenesis – new opportunities for neurological treatment? Reports from experimental studies.

Drab¹,

Haratym-Maj²,

Zagaja³

et al. 2017

J Pre Clin Clin Res.

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Neurogenesis is one of the most important phenomenona affecting human life. This process consists of proliferation, migration and differentiation of neuroblasts and synaptic integrations of newborn neurons. Proliferation of new cells continues into old age, also in humans, although the most extensive process of cell formation occurs during the prenatal period. It is possible to distinguish two regions in the brain responsible for neurogenesis: the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ). Hippocampal neurogenesis is very sensitive to various physiological and pathological stimuli. The functional integration of the newly-born dentate granule cells into hippocampal circuitry, and their ability to mediate long-term potentiation in DG, has led to the hypothesis that neurogenesis in the adult brain may play a key role in learning and memory function, as well as cognitive dysfunction in some diseases. Brain disorders, such as neurodegenerative diseases or traumatic brain injuries, significantly affect migration, proliferation and differentiation of neural cells. In searching for the best neurological drugs protecting neuronal cells, stimulating neurogenesis, while also developing no side-effects, endocannabinoids proved to be a strong group of substances having many beneficial properties. Therefore, the latest data is reviewed of the various experimental studies concerning the analysis of the most commonly studied cannabinoids and their impact on neurogenesis.

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Section: Neurogenesis and Cannabinoidssupporting

confidence: 61%

Endocannabinoid system and cannabinoids in neurogenesis – new opportunities for neurological treatment? Reports from experimental studies.

Drab¹,

Haratym-Maj²,

Zagaja³

et al. 2017

J Pre Clin Clin Res.

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“…Furthermore, addition of DHA to DHA-deficient embryonic hippocampal neurons in culture can restore neurite length [174]. Recent studies indicate that endogenous metabolism of DHA to N -docosahexaenoylethanolamine (synaptamide) is primarily responsible for the observed DHA effects on neurite growth, synaptogenesis and neurogenesis [177,178]. Nevertheless, the DHA-induced PS increase and facilitation of PS-dependent signaling pathways leading to neuronal differentiation may also be a contributing mechanism for the observed DHA effects [5].…”

Section: Interactions Between Phosphatidylserine and Docosahexaenomentioning

confidence: 99%

Phosphatidylserine in the brain: Metabolism and function

Kim

Huang

Spector

2014

Progress in Lipid Research

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264

180

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Phosphatidylserine (PS) is the major anionic phospholipid class particularly enriched in the inner leaflet of the plasma membrane in neural tissues. PS is synthesized from phosphatidylcholine or phosphatidylethanolamine by exchanging the base head group with serine in reactions are catalyzed by phosphatidylserine synthase 1 and phosphatidylserine synthase 2 located in the endoplasmic reticulum. Activation of Akt, Raf-1 and protein kinase C signaling, which supports neuronal survival and differentiation, requires interaction of these proteins with PS localized in the cytoplasmic leaflet of the plasma membrane. Furthermore, neurotransmitter release by exocytosis and a number of synaptic receptors and proteins are modulated by PS present in the neuronal membranes. Brain is highly enriched with docosahexaenoic acid (DHA), and brain PS has a high DHA content. By promoting PS synthesis, DHA can uniquely expand the PS pool in neuronal membranes and thereby influence PS-dependent signaling and protein function. Ethanol decreases DHA-promoted PS synthesis and accumulation in neurons, which may contribute to the deleterious effects of ethanol intake. Improvement of some memory functions has been observed in cognitively impaired subjects as a result of PS supplementation, but the mechanism is unclear.

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“…EPA and DHA enhance adult hippocampal neurogenesis in a variety of animal models (Dyall, 2011b) and DHA has consistently been shown to promote differentiation of neural stem cells (NSCs) (Katakura et al, 2009;Kawakita et al, 2006;Ma et al, 2010;Rashid et al, 2013). Elucidating the mechanisms behind these effects has been complicated by the convergent pathways involved in regulating neurogenesis and the pleiotropic effects of omega-3 PUFAs.…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 98%

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

et al. 2016

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Running title: EPA, but not DHA induces proliferation in NSCs Abbreviations: AA, Arachidonic acid, AEA, anandamide, DHA. Docosahexaenoic acid; EPA, eicosapentaenoic acid, 2-AG, 2-arachidonylglycerol 2 Title: Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways Emerging evidence suggests a complex interplay between the endocannabinoid system, omega-3 fatty acids and the immune system in the promotion of brain self-repair. However, it is unknown if all omega-3 fatty acids elicit similar effects on adult neurogenesis and if such effects are mediated or regulated by interactions with the endocannabinoid system. This study investigated the effects of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid signalling pathways in these effects.EPA, but not DHA, significantly increased proliferation of NSCs compared to controls, an effect associated with enhanced levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK, effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor antagonists. Furthermore, in NSCs derived from IL-1 deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1 signalling in the effects observed. Although DHA similarly increased 2-AG levels in wild-type NSCs, there was no concomitant increase in proliferation or p-p38 MAPK activity. In addition, in NSCs from IL-1 deficient mice, DHA significantly increased proliferation without effects on p-P38 MAPK, suggesting effects of DHA are mediated via alternative signalling pathways. These results provide crucial new insights into the divergent effects of EPA and DHA in regulating NSC proliferation and the pathways involved, and highlight the therapeutic potential of their interplay with endocannabinoid signalling in brain repair.

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N‐docosahexaenoylethanolamine is a potent neurogenic factor for neural stem cell differentiation

Cited by 86 publications

References 53 publications

Endocannabinoid system and cannabinoids in neurogenesis – new opportunities for neurological treatment? Reports from experimental studies.

Endocannabinoid system and cannabinoids in neurogenesis – new opportunities for neurological treatment? Reports from experimental studies.

Phosphatidylserine in the brain: Metabolism and function

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

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