Dietary enrichment with omega-3 polyunsaturated fatty acids reverses age-related decreases in the GluR2 and NR2B glutamate receptor subunits in rat forebrain

Dyall, Simon C.; Michael, G.J.; Whelpton, Robin; Scott, Alan G.; Michael‐Titus, Adina T.

doi:10.1016/j.neurobiolaging.2006.01.002

Cited by 109 publications

(82 citation statements)

References 69 publications

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“…UMP and DHA administration increases brain phosphatide levels [14], and the density of hippocampal dendritic spines, [41] which require additional synaptic membrane. DHA administration reversed the age-related decline in GluR2 and NR2B glutamate receptor subunits, thereby improving glutamatergic transmission in the hippocampus [42]. In support of this proposed interpretation, we confirmed prior [14] findings that administration of UMP and DHA increases brain phosphatide levels (table 1) and concurrently protect IC rats from memory impairment (figure 1).…”

Section: Discussionsupporting

confidence: 88%

Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats

Holguin

Huang

Liu

et al. 2008

Behavioural Brain Research

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Living in an enriched environment (EC) during development enhances memory function in adulthood; living in an impoverished environment (IC) impairs memory function. Compounds previously demonstrated to improve memory among IC rats include CDP-choline and uridine monophosphate (UMP). Brain phosphatidylcholine (PC) synthesis utilizes both the uridine formed from the metabolism of exogenous CDP-choline and UMP, and the choline formed from that of CDPcholine. It also uses the polyunsaturated fatty acid (PUFA) DHA, a precursor for the diacylglycerol incorporated into PC. DHA administration also improves cognition in young and aged rodents and humans; its effects on cognitively-impaired IC rats have not been characterized. We have thus examined the consequences of administering DHA (300 mg/kg ) by gavage, UMP (0.5% in the diet), or both compounds on hippocampal-and striatal-dependent forms of memory among rats exposed to EC or IC conditions for 1 month starting at weaning, and consuming a choline-containing diet. We observe that giving IC rats either dietary UMP or gavaged DHA improves performance on the hidden version of the Morris water maze (all P<0.05), a hippocampal-dependent task; coadministration of both phosphatide precursors further enhances the IC rats' performance on this task (P<0.001). Neither UMP, DHA, nor both compounds affects the performance of EC rats on the hidden version of the Morris water maze (P>0.05), nor the performance by IC or EC rats on the visible version of the Morris water maze (all P>0.05), a striatal-dependent task. We confirm that coadministration of UMP and DHA to rats increases brain levels of the phosphatides PC, PE, SM, PS, PI, and total brain phospholipid levels (all p<0.05), and show that rearing animals in an enriched environment also elevates brain PC, PS, and PI levels (all p<0.01) and total brain phospholipids (p<0.01) compared with their levels in animals reared in an IC environment. These findings suggest that giving DHA plus UMP can ameliorate memory deficits associated with rearing under impoverished conditions, and that this effect may be mediated in part through enhanced synthesis of brain membrane phosphatides.

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Section: Discussionsupporting

confidence: 88%

Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats

Holguin

Huang

Liu

et al. 2008

Behavioural Brain Research

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“…On the other hand, an imbalance between glutamatergic and GABAergic transmission was found after IL-1 administration (Zhu et al, 2006). After EPA treatment, the reduction of glutamate-induced excitotoxicity and attenuation of age-related decreases in the GluR2 and NR2B glutamate receptors have been reported in the rat (Xiao and Li, 1999;Dyall et al, 2007). Therefore, possible mechanisms by which EPA improves spatial memory in OB rats may result from EPA's suppression of inflammation and normalization of the cholinergic and glutamatergic systems.…”

Section: Discussionmentioning

confidence: 99%

Increased Phospholipase A2 Activity and Inflammatory Response But Decreased Nerve Growth Factor Expression in the Olfactory Bulbectomized Rat Model of Depression: Effects of Chronic Ethyl-Eicosapentaenoate Treatment

Song¹,

Zhang²,

Manku³

2009

J. Neurosci.

167

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An increased inflammatory response and deficient synthesis of neurotrophic factors (NTFs) may contribute to the etiology of depression. However, the interrelationship between inflammation and NTFs is unknown. Recently, ethyl-eicosapentaenoate (EPA) has been used to treat depression. The mechanism by which EPA benefits depression is also unclear. Using the olfactory bulbectomized (OB) rat model of depression, this study evaluated two pathways from bulbectomy to the induction of depression-like changes (the inflammation-hypothalamic-pituitary-adrenal axis-stress response pathway and inflammation-nerve growth factor-memory pathway) and the effect of EPA on these pathways. When compared with sham-operated rats fed a control diet, significantly increased locomotor and rearing activities in an "open field," impaired memory in the Morris water maze, increased expression of corticotrophin-releasing factor (CRF), and increased secretion of corticosterone were found in OB rats. mRNA expression of nerve growth factor (NGF) was significantly lower in the hippocampus, and phospholipase A2 (PLA2) was higher in the hypothalamus; this change was associated with increased interleukin-1␤ (IL-1␤) and prostaglandin E2 (PGE2) in the serum and brain. EPA treatments normalized these behavioral impairments and reduced CRF expression and corticosterone secretion. EPA also reduced serum concentrations of IL-1␤ and PGE2, but reversed NGF reduction. Similar to the effects of EPA, the anti-inflammatory drug celecoxib significantly reduced blood PGE2, IL-1␤, and corticosterone concentrations and increased NGF expression in OB rats. Furthermore, anti-NGF treatment blocked EPA effects on behavior. These results suggest that an interaction exists between inflammation and NGF in the depression model. EPA may improve depression via its anti-inflammation properties and the upregulation of NGF.

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“…The incorporation of DHA and EPA into the membrane phospholipids of the NSCs from wild type and IL-1 knock-out mice was assessed as described previously (Dyall et al, 2007).…”

Section: Fatty Acid Analysismentioning

confidence: 99%

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

et al. 2016

Self Cite

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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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Dietary enrichment with omega-3 polyunsaturated fatty acids reverses age-related decreases in the GluR2 and NR2B glutamate receptor subunits in rat forebrain

Cited by 109 publications

References 69 publications

Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats

Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats

Increased Phospholipase A2 Activity and Inflammatory Response But Decreased Nerve Growth Factor Expression in the Olfactory Bulbectomized Rat Model of Depression: Effects of Chronic Ethyl-Eicosapentaenoate Treatment

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

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