INTRODUCTION:

Omega-3 fatty acids are long chain, polyunsaturated fatty acids (PUFA) of plant and marine origin. Because these essential fatty acids (EFAs) cannot be synthesized in the human body, they must be derived from dietary sources. Flaxseed, hemp, canola, and walnuts are generally rich sources of the omega-3 PUFA alpha-linolenic acid (ALA). Fish provide varying amounts of omega- 3 fatty acids in the form of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). ALA can be metabolized into the longer chain EPA and DHA (1). According to the Institute of Medicine of the National Academies, omega-3 Fatty acids “play an important role as structural membrane lipids, particularly in nerve tissue and the retina (2, 3). Omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are now widely recognized as having important biological roles in reducing cardiovascular mortality, and the American Heart Association includes them in their dietary recommendations (4). Omega-3 fatty acids are important for optimal brain function during infancy.

The brain contains a high concentration of PUFA (approximately 20 percent of dry weight) and, in the nervous system, one out of every three fatty acids (FAs) belong to the PUFA group (5). Recent research underscores the important role of these fatty acids in central nervous system (CNS) function, and the potential EFAs have in the treatment of various neuropsychiatric disorders. While beneficial effects of omega-3 fatty acids have been linked to Alzheimer’s disease (6) attention deficit hyperactivity disorder (7), autism (8), schizophrenia (9), hostility(10), anxiety (11) and bipolar disorder (12), the focus of this article will be the role of omega-3 fatty acids in the neurobiology and treatment of major depressive disorder. The Canadian Government has recognized the importance of DHA omega-3 and permits the following biological role claim for DHA: "DHA, an omega-3 fatty acid, supports the normal development of the brain, eyes and nerves (13). DHA is a major structural component of the mammalian brain, and is in fact the most abundant omega-3 fatty acid in the brain (14).

Chemistry of Omega -3 fatty acids:

Omega-3 fatty acids are components of fats in foods we eat. The term omega and number three refer to the chemical structure of the fatty acid. There are three main omega-3 fatty acids:

1.) Alpha- linolenic acid (ALA): It is the most common omega-3 fatty acid in the western diet. It comes from plants, and is found in vegetable oils, primarily flaxseed, walnut, canola and soybean oils. ALA is a dietary essential fatty acid; we must eat it because our bodies require ALA but cannot make it and use it to form the functionally essential omega-3 fatty acids, EPA and DHA. Although the American diet contains the recommended amount of ALA, it is not well converted to EPA and DHA. Therefore, preformed EPA and DHA are required for optimal health in most people, especially during periods of rapid growth and development such as pregnancy and in the first year of life.

2.) Eicosapentaenoic acid (EPA) and, 3.) Docosahexaenoic acid (DHA) is known as the “long-chain” or marine omega-3 fatty acids since they are mainly found in fish and fish oils. EPA and DHA have the most potent health benefits of the omega-3 fatty acids. Unfortunately, they are especially low in the American diet, and since conversion of ALA to EPA and DHA is poor, increasing intake of EPA and DHA has the potential to significantly improve health.

Biological mechanisms of Omega -3 pufa:

Several biological mechanisms potentially explain the impact of omega essential fatty acids in psychiatric disorder may include:

1. Increase serotonergic neurotransmissions (15, 16).

2. Alterations in dopaminergic function (17, 18)

3. Regulation of corticotrophin – releasing factor (19)

4. Inhibition of protein kinase C (20)

5. Suppression of phosphatidylinositol - associated second messenger activity (21)

6. Modulation of heart rate variability via vagal mechanism (22)

7. Increased dendritic arborization and synapse formation (23)

8. Prevention of neuronal apotosis (24)

9. Improved cerebral blood flow (25)

10. Regulation of gene expression (26,27)

11. Competition of EPA with AA for enzymatic action and resultant reduction of the inflammatory response (28).

Hippocampus:

Hippocampus, the earliest description of the ridge running along the floor of the temporal horn of the lateral ventricle comes from the Venetian anatomist Julius Caesar Aranzi (1587), who initially likened it to a silkworm, and then a seahorse (Figure 1). The German anatomist Duvernoy (1729), the first to illustrate the structure, also wavered between "seahorse" and "silkworm." "Ram's horn" was proposed by the Danish anatomist Jacob Winslow in 1732; and a decade later his fellow Parisian, the surgeon de Garengeot, used "cornu Ammonis" - horn of (the ancient Egyptian god) Amun. Today, the structure is called the hippocampus (29).

Figure: 1

Anatomically, the hippocampus (figure: 2), is an elaboration of the edge of the cerebral cortex(30) can be distinguished as a zone where the cortex narrows into a single layer of very densely packed neurons, which curls into a tight S shape. The structures that line the edge of the cortex make up the so-called limbic system (Latin limbus = border): these include the hippocampus, cingulated cortex, olfactory cortex, and amygdale (31). The hippocampus as a whole has the shape of a curved tube, which has been analogized variously to a seahorse, a ram's horn (Cornu Ammonis, hence the subdivisions CA1 through CA4), or a banana (30). It consists of ventral and dorsal portions, both of which share similar composition but are parts of different neural circuits (32). This general layout holds across the full range of mammalian species, from hedgehog to human, although the details vary. In the rat, the two hippocampi resemble a pair of bananas, joined at the stems. In human or monkey brains, the portion of the hippocampus down at the bottom, near the base of the temporal lobe, is much broader than the part at the top. One of the consequences of this complex geometry is that cross-sections through the hippocampus can show a variety of shapes, depending on the angle and location of the cut (30).

Figure: 2

Historically, the earliest widely held hypothesis was that the hippocampus is involved in olfaction. This idea was largely motivated by a belief, later shown to be false, that the hippocampus receives direct input from the olfactory bulb (33). There continues to be some interest in hippocampal olfactory responses, particularly the role of the hippocampus in memory for odors, but few people believe today that olfaction is its primary function (34, 35)

Over the years, three main ideas of hippocampal function have dominated the literature: inhibition, memory, and space. The behavioral inhibition theory (caricatured by O'Keefe and Nadel as "slam on the brakes!") (36), was very popular up to the 1960s. It derived much of its justification from two observations: first, that animals with hippocampal damage tend to be hyperactive; second, that animals with hippocampal damage often have difficulty learning to inhibit responses that they have previously been taught. Jeffrey Gray developed this line of thought into a full-fledged theory of the role of the hippocampus in anxiety (37).

Omega -3 pufa and hippocampal neurogenesis:

Omega-3 polyunsaturated fatty acids have essential role in brain development and function and beneficial effects of omega-3 PUFA treatment have consistently been demonstrated in a variety of hippocampal-dependent tasks. For example, omega-3 PUFAs enhance spatial memory tasks in adult and old rats (38), possess anti-depressant effects (39), increase synaptogenesis (40) and enhance hippocampal neurite outgrowth (41). However, the mechanisms underlying these effects are still unclear. Omega-3 PUFAs have been shown to influence developmental neurogenesis, where several studies have reported that omega-3 PUFA deficiency in embryonic and newborn rats leads to decreased neurogenesis and delay or inhibition of normal development (42, 43, 44). It may therefore be hypothesised that omega-3 PUFA may enhance hippocampal function via effects on adult neurogenesis. The first published evidence of omega-3 PUFAs enhancing adult hippocampal neurogenesis was provided by Kawakita and co-workers (44). In this study adult rats were fed docosahexaenoic acid (DHA) at 300 mg/kg for seven weeks. DHA treatment significantly increased the number of BrdU positive and NeuN positive newborn neurons in dentate gyrus, indicating enhanced neuronal proliferation and maturation. In the second part of the study, neural stem cells were cultured under differential conditions with or without DHA for 4 and 7 days. DHA significantly increased the number of Tuj1-positive neurons compared with the control groups on both culture days, and the newborn neurons in the DHA group were morphologically more mature than in the control group. DHA also significantly decreased the incorporation ratio of BrdU during the first 24 h period; it also significantly decreased the number of pyknotic (degenerating) cells on day 7, indicating that DHA promotes the differentiation of neural stem cells into neurons by promoting cell cycle exit and suppressing cell death.

Role of hippocampal neurogenesis in memory consolidation:

In rodents, primates, human, dentate gyrus in the hippocampus of the two brain regions with lifelong neurogenesis. Despite the wealth of accumulating data on the characteristics of neurons in newborns, the specific contribution of their generation to memory formation by hippocampus remains unclear (45). Recently, Kitamura and colleagues showed that severe impairment of hippocampal neurogenesis attenuated the loss of hippocampus- dependent Remote contextual fear in mice, while conversely, exercise on running wheel, which promotes neurogenesis, increased the rate of loss of hippocampus- dependent contextual fear memory (46). The hippocampus -dependent periods for fear memory are modulated by various conditions. Independent lines of evidence strongly suggest that the level of hippocampal neurogenesis plays a role in determining the hippocampus-dependent period of memory in adult rodents. In short, the level of hippocampal neurogenesis was able to be modulated and in associated with a causal relationship between adult neurogenesis and the hippocampal dependent period of fear memory. Therefore it is theoretically possible that promoting adult neurogenesis early in transition might facilitate the clearance of fear memory from hippocampus.

CONCLUSION:

Hence Omega -3 fatty acids have medical benefits on preventing from heart disease, diabetes, also against Dementia and Alzheimer’s diseases and slows ageing and reduces depression levels, risk of cancer and improves blood cholesterol level and bone strength. Many researchers have been processed to known well about the medicinal benefits on humans as well as in animal. While there is evidence that essential fatty acids play a biological role in depression, there is very little published data. Fish oil supplements are usually well tolerated, with an impressive long term safety record at doses of 1 g daily. Clinical studies show that Omega has good anti-inflammatory properties. More researches are required to explore the “Effect of Omega-3 fatty acids”.

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Received on 16.03.2014 Modified on 25.04.2014

Research J. Pharm. and Tech. 7(6): June, 2014; Page 715-718