Modification by docosahexaenoic acid of age-induced alterations in gene expression and molecular composition of rat brain phospholipids

Abstract

Advanced age is associated with reduced brain levels of long-chain polyunsaturated fatty acids, arachidonic acid (AA) and docosahexaenoic acid (DHA). Memory impairment is also a common phenomenon in this age. Two-year-old, essential fatty acid-sufficient rats were fed with fish oil (11% DHA) for 1 month, and fatty acid as well as molecular composition of the major phospholipids, phosphatidylcholine and phosphatidylethanolamine (PE), was compared with that of 2-month-old rats on the same diet. DHA but not AA was significantly reduced in brains of old rats but was restored to the level of young rats when they received rat chow fortified with fish oil. This effect was pronounced with diacyl 18:0͞22:6 PE species, whereas levels of 18:1͞22:6 and 16:0͞22:6 remained unchanged in all of the three PE subclasses. Fish oil reduced the AA in the old rat brains, diacyl and alkenylacyl 18:0͞20:4 PE being most affected. Phosphatidylcholines gave less pronounced response. Six genes were up-regulated, whereas no significant changes were observed in brains of old rats receiving fish oil for 1 month. None of them except synuclein in young rat brains could be related to mental functions. Old rats on the fish-oil diet did not perform better in Morris water maze test than the control ones. A 10% increase in levels of diacyl 18:0͞22:6 PE in young rat brains resulted in a significant improvement of learning capacity. The results are interpreted in terms of the roles of different phospholipid molecular species in cognitive functions coupled with differential responsiveness of the genetic machinery of neurons to n-3 polyunsaturated fatty acids.B rain is one of the organs rich in phospholipids, which provide the building blocks for different membrane structures. These phospholipids are rather rich in long-chain polyunsaturated fatty acids, particularly in docosahexaenoic acid (DHA) and arachidonic acid (AA). DHA content of brain phospholipids seems to be precisely controlled. It is determined during pregnancy and early postnatal life (1, 2). There is a consensus that after this time it is almost impossible to alter brain fatty acid composition of adult, essential fatty acid-sufficient rats. On the other hand, any imbalance in polar head group or fatty-acid composition of structural lipids might have consequences on mental performance. Loss in DHA in brains of persons with Alzheimer's disease is accompanied with loss of memory and learning (3). In aged persons, impairment of memory also often takes place, and this is accompanied with loss of DHA in their brains (4-6). It has been shown that chronic administration of DHA to essential fatty acid-deficient young rats restores DHA levels in brain and improves memory (7). Similarly, DHA administration to ischemic rats had beneficial effect on spatial cognitive deficit (8). Moriguchi et al. (9) showed also that full recovery of brain DHA in essential fatty acid-deficient rats was obtained after 8 weeks on a DHA-containing diet. Hashimoto et al. (10) demonstrated that DHA provided protection fr...

Effect of Zinc and DHA on Expression Levels and Post-Translational Modifications of Histones H3 and H4 in Human Neuronal Cells

“…Conversely, DHA was found to upregulate H3 and H4 expression levels and abolished the effect of zinc, suggesting the potential contribution of DHA in increasing DNA synthesis, which result in the increase of histone protein levels. Our results are supported by previous studies, by which zinc regulates a variety of transcription and translation related factors, including the H3 histone family 3A protein (Barcelo-Coblijn, Hogyes et al 2003). Since there's association between alteration in histone subunit expression and DNA replication, the condition may then alter the expression of many other genes.…”

Proteins in Human Brain Cortex Are Modified by Oxidation, Glycoxidation, and Lipoxidation

“…It is known that A␤ induces hippocampal neuronal death by a mechanism that requires lipid peroxidation (39). Disturbances in the metabolism and transport of essential fatty acids may explain the observed changes (40), but they could also originate from a defensive response, because of the neuroprotective role of DHA in several experimental models (41). However, this may be a double-edged sword, as DHA is a highly peroxidizable fatty acid.…”

Low liver conversion rate of α-linolenic to docosahexaenoic acid in awake rats on a high-docosahexaenoate-containing diet

“…Clearly, the liver a-LNA concentration depends on dietary a-LNA. Additionally, the conversion of a-LNA to DHA depends on the dietary content of n-3 PUFAs (4,(65)(66)(67)(68). One reason for this is that the transcription of genes for the D5 and D6 desaturases is influenced by n-3 PUFA levels (69).…”