Eicosapentaenoic acid stimulates the expression of myelin proteins in rat brain

Abstract

We have previously demonstrated that, in C6 glioma cells, eicosapentaenoic acid (EPA) stimulates the expression of proteolipid protein (PLP) via cAMP-mediated pathways. In this study, we investigated whether n-3 polyunsaturated fatty acids can affect myelinogenesis in vivo. A single dose of either EPA or docosahexaenoic acid (DHA) was injected intracerebroventricularly into 2-day-old rats, which were then killed after 3 days post-injection (p.i.). Total RNA was isolated from the medulla, cerebellum, and cortex, and the expression of myelin-specific mRNAs was analyzed by real-time PCR. The levels of PLP, myelin basic protein, and myelin oligodendrocyte protein mRNAs increased in nearly all brain regions of DHA- and EPA-treated animals, but the effect was more pronounced in EPA-treated rats. The enhancement in PLP transcript levels was followed by an increase in PLP translation in EPA-treated rats. A further indicator of accelerated myelination was the increase in 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) protein levels. In EPA-treated rats, the increased expression of myelin genes coincided with a decrease of cAMP-response element-binding protein (CREB)-DNA binding in the cerebellum and cortex (1 hr p.i.). After 16 hr, this effect was still present in the same cerebral regions even though the decrease in EPA-treated rats was less pronounced than in controls. The down-regulation of CREB activity was due to a decrease in the levels of CREB phosphorylation. In conclusion, our data suggest that EPA stimulates the expression of specific myelin proteins through decreased CREB phosphorylation. These results corroborate the clinical studies of the n-3 PUFA beneficial effects on several demyelinating diseases.

Deficits in Docosahexaenoic Acid Accrual during Adolescence Reduce Rat Forebrain White Matter Microstructural Integrity: An in vivo Diffusion Tensor Imaging Study

“…Meta-analyses indicate that schizophrenia [27], bipolar disorder [28], and unipolar depression [29] are associated with PUFA deficits including DHA. Preclinical studies further suggest that n-3 PUFAs promote oligodendrocyte maturation and myelin expression [30,31], and are protective against axonal WM injury induced by trauma [32] and inflammation [33,34]. However, other studies suggest that maternal n-3 PUFA supplementation or deficiency impair neonatal axonal conduction, which is consistent with dysmyelination [35][36][37].…”

Docosahexaenoic Acid Pretreatment Confers Protection and Functional Improvements after Acute Spinal Cord Injury in Adult Rats

“…For instance, DHA and its derivatives show anti-inflammatory (De Smedt-Peyrusse et al, 2008;Ló pez-Vales et al, 2010;Mullen et al, 2010), and neuroprotective attributes (Bazan, 2006(Bazan, ,2005Belayev et al, 2009). Moreover, DHA activates both Akt and CREB, which have been associated with neuroprotection and myelin stability in vitro and in vivo (Akbar et al, 2005;Mukherjee et al, 2004;Salvati et al, 2008;Wu et al, 2008). These beneficial effects have been reported in a number of neurological studies (Lauritzen et al, 2000;Lim et al, 2005;Pan et al, 2009;Rodriguez de Turco et al, 2002), including SCI (Huang et al, 2007;King et al, 2006;Lang-Lazdunski et al, 2003;Ward et al, 2010).…”

“…Akt and CREB have been associated with DHA protective effects on survival and myelin stability in vitro and in vivo (Akbar et al, 2005;Mukherjee et al, 2004;Salvati et al, 2008;Wu et al, 2008). We examined whether DHA pretreatment increases the mRNA and protein phosphorylation levels of Akt and CREB after acute SCI.…”

Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children

“…Another mechanism by which LC-PUFAs-especially ω-3 fatty acids-exert their function in the nervous system is their potential to regulate brain gene expression, as experimental studies conducted in recent years have shown [12,66,108]. LC-PUFAs are therefore a prime example of the close interaction between nutrients and genetic factors.…”