Fatty Acids: From Membrane Ingredients to Signaling Molecules

Fatty acid constitutes the foundation cell membranes, provides metabolic energy, affects functions of membrane-bound enzymes/receptors, conducts signaling cascades, and helps in learning-related memory cognition in mammals, including humans. Structurally, the fatty acids are of two kinds: saturated and unsaturated; the latter are again of mono- and polyunsaturated types. From nutritional perspectives, they are of essential and nonessential types. Omega-6 linoleic acid (ω-6 LLA, C18:2) and ω-3 alpha linolenic acid (ω-3 αLLN, C18:3) and ω-6 arachidonic acid [(ω-6 AA, C20:4); it is conditional] are essential fatty acids (EFAs). In addition, mammalian brains cannot biosynthesize the ω-3 docosahexaenoic acid (ω-3 DHA, C22:6) in adequate amounts because of lack of necessary enzymes. Thus, DHA is essential for the growth and development of the brains. Deficiency of DHA produces visual- and learning-related memory impairments, and neurodegeneration in the aged brains and Alzheimer’s disease brains. Finally, this chapter will highlight and broaden the awareness about the essentiality of different fatty acids with a special emphasis on DHA

Validation of Ganoderma lucidum against hypercholesterolemia and Alzheimer’s disease

Ganoderma lucidum has been hailed as medicinal mushroom. Its effect on memory and learning related behavioral performance along with related protein markers has been evaluated using Alzheimer’s disease (AD) and hypercholesterolemic model rats in the present study. AD model rats were prepared infusing amyloid beta peptide into the right ventricles of the rats. Hypercholesterolemia was evoked feeding 1% cholesterol and 1% cholic acid with basal diet of the rats for 8 weeks. Hot water extract of G. lucidum was ingested orally (200 mg/kg bw) to the HC and AD model rats. Memory and learning related behavioral tests were performed using Barnes maze while protein markers (BDNF, SNAP2, PSD-95, VAchT) were detected using ELISA. Observed findings suggest hypocholesterolemic, lipid profile improving and enhanced cognitive performance of the G. lucidum fed rats. Memory and learning related protein markers also substantiate this fruition. Thus, therapeutic potentiality of Ganoderma lucidum in AD amelioration seems promising. DOI: http://dx.doi.org/10.5281/zenodo.400958

Effects of hydrogen-rich water on abnormalities in a SHR.Cg-Leprcp/NDmcr rat - a metabolic syndrome rat model

<p>Abstract</p> <p>Background</p> <p>Hydrogen (H₂), a potent free radical scavenger, selectively reduces the hydroxyl radical, which is the most cytotoxic of the reactive oxygen species (ROS). An increase in oxygen free radicals induces oxidative stress, which is known to be involved in the development of metabolic syndrome. Therefore, we investigated whether hydrogen-rich water (HRW) affects metabolic abnormalities in the metabolic syndrome rat model, SHR.Cg-<it>Lepr^cp</it>/NDmcr (SHR-cp).</p> <p>Methods</p> <p>Male SHR-cp rats (5 weeks old) were divided into 2 groups: an HRW group was given oral HRW for 16 weeks, and a control group was given distilled water. At the end of the experiment, each rat was placed in a metabolic cage for 24 h, fasted for 12 h, and anesthetized; the blood and kidneys were then collected.</p> <p>Results</p> <p>Sixteen weeks after HRW administration, the water intake and urine flow measured in the metabolic cages were significantly higher in the HRW group than in the control group. The urinary ratio of albumin to creatinine was significantly lower and creatinine clearance was higher in the HRW group than in the control group. After the 12-h fast, plasma urea nitrogen and creatinine in the HRW group were significantly lower than in the control group. The plasma total antioxidant capacity was significantly higher in the HRW group than in the control group. The glomerulosclerosis score for the HRW group was significantly lower than in the control group, and a significantly positive correlation was observed between this score and plasma urea nitrogen levels.</p> <p>Conclusion</p> <p>The present findings suggest that HRW conferred significant benefits against abnormalities in the metabolic syndrome model rats, at least by preventing and ameliorating glomerulosclerosis and creatinine clearance.</p

Raphanus sativus ameliorates atherogeneic lipid profiles in hypercholesterolemic rats and hypercholesterolemia-associated peroxidative liver damage

Objective: Raphanus sativus is a hugely used edible root vegetable. We investigated whether the feeding of the Raphanus sativus hot water extract (RSE) ameliorates atherogenic lipid profile and oxidative stress in hypercholesterolemia. Methods: After feeding of the RSE to hypercholesterolemic rats for 6 weeks, the levels of plasma and hepatic total cholesterol (TC), triglyceride (TG), and plasma high density lipoprotein-cholesterol (HDL-C) and fecal TC levels were studied. The effects of RSE on the hepatic enzymes, namely alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), the levels of lipid peroxide (LPO) and liver histology were also evaluated. Results: Hypercholesterolemia increased the levels of TC and TG in the plasma and livers. The levels of ALT, AST and ALP in plasma and LPO in the liver also increased. The dietary RSE, however, significantly ameliorated the above atherogenic lipids and liver enzymes. The RSE significantly reduced the levels of LPO in the liver, suggesting an in vivo protection against of oxidative stress. The RSE also inhibited the in vitro Fenton’s reagent-induced oxidative stress, thus corroborating the in vivo anti-LPO actions of RSE. The levels of hepatic LPO were positively correlated with plasma AST (r=0.76; P &lt;0.05) and ALT (r=0.43; P&lt;0.05) levels. Histologically, the livers of the RSE-fed hypercholesterolemic rats exhibited lesser fatty droplets and reduced inflammatory cells. Conclusion: Finally, R. sativus extract lowers the cardiovascular disease risk factors under hypercholesterolemic situation by increasing the plasma/hepatic clearance of cholesterol and improving the hypercholesterolemia-induced oxidative damage of hepatic tissues

Omega-3 Polyunsaturated Fatty Acids Enhance Neuronal Differentiation in Cultured Rat Neural Stem Cells

Polyunsaturated fatty acids (PUFAs) can induce neurogenesis and recovery from brain diseases. However, the exact mechanisms of the bene�cial effects of PUFAs have not been conclusively described. We recently reported that docosahexaenoic acid (DHA) induced neuronal differentiation by decreasing Hes1 expression and increasing p27 kip1 expression, which causes cell cycle arrest in neural stem cells (NSCs). In the present study, we examined the effect of eicosapentaenoic acid (EPA) and arachidonic acid (AA) on differentiation, expression of basic helix-loop-helix transcription factors (Hes1, Hes6, and NeuroD), and the cell cycle of cultured NSCs. EPA also increased mRNA levels of Hes1, an inhibitor of neuronal differentiation, Hes6, an inhibitor of Hes1, NeuroD, and Map2 mRNA and Tuj-1-positive cells (a neuronal marker), indicating that EPA induced neuronal differentiation. EPA increased the mRNA levels of p21 cip1 and p27 kip1 , a cyclin-dependent kinase inhibitor, which indicated that EPA induced cell cycle arrest. Treatment with AA decreased Hes1 mRNA but did not affect NeuroD and Map2 mRNA levels. Furthermore, AA did not affect the number of Tuj-1-positive cells or cell cycle progression. ese results indicated that EPA could be involved in neuronal differentiation by mechanisms alternative to those of DHA, whereas AA did not affect neuronal differentiation in NSCs

Early versus late rehabilitation for stroke survivors: A prospective study

The aim of this study was to examine the optimum time of rehabilitation initiation after stroke in terms of disabilities, mobility and fall risk assessment. Data were collected prospectively at seven tertiary level health care centers in Bangladesh during the 36 months period from 2013 to 2016. All respondents were divided into four groups based on the initiation of rehabilitation as: a) 0-24 hours, b) 25-72 hours, c) 4-7 days and d) 8-60 days. Results show that significant improvement on stroke recovery, disabilities reduction, improvement in mobility restriction and reduction of fall risks in all the four groups but more improvement was observed in 0-24 hour’s group during follow-up after 3 and 12 weeks. On multinomial logistic regression analysis, the independent factors shows the mobility restriction and fall risk were more in the younger patients, male gender, married, hemorrhagic lesion and bilateral stroke

Docosahexaenoic Acid Helps to Lessen Extinction Memory in Rats

Abstract: Memory extinction is referred to as a learning process in which a conditioned response (CR) progressively reduces over time as an animal learns to uncouple a response from a stimulus. Extinction occurs when the rat is placed into a context without shock after training. Docosahexaenoic acid (DHA, C22:6, n-3) is implicated in memory formation in mammalian brains. In a two-way active shuttle-avoidance apparatus, we examined whether DHA affects the extinction memory and the expression of brain cognition-related proteins, including gastrin-releasing peptide receptor (GRPR), brain-derived neurotrophic factor receptor (BDNFR) tyrosine kinase receptor B (TrKB), and N-methyl-d-aspartate receptor (NMDAR) subunits NR2A and NR2B. Also, the protein levels of GRP, BDNF, postsynaptic density protein-95 (PSD-95), and vesicular acetylcholine transporter (VAChT), and the antioxidative potentials, in terms of lipid peroxide (LPO) and reactive oxygen species (ROS), were examined in the hippocampus. During the acquisition phase, the rats received a conditioned stimulus (CS-tone) paired with an unconditioned stimulus (UCS foot shock) for three consecutive days (Sessions S1, S2, and S3, each consisting of 30-trials) after 12 weeks of oral administration of DHA. After a three-day interval, the rats were re-subjected to two extinction sessions (S4, S5), each comprising 30 trials of CS alone. During the acquisition training in S1, the shock-related avoidance frequency (acquisition memory) was significantly higher in the DHA-administered rats compared with the control rats. The avoidance frequency, however, decreased with successive acquisition trainings in sessions S2 and S3. When the rats were subjected to the extinction sessions after a break for consolidation, the conditioned response (CR) was also significantly higher in the DHA-administered rats. Interestingly, the freezing responses (frequency and time) also significantly decreased in the DHA-administered rats, thus suggesting that a higher coping capacity was present during fear stress in the DHA-administered rats. DHA treatments increased the mRNA levels of GRPR, BDNF receptor TrKB, and NMDAR subunit NR2B. DHA also increased the protein levels of GRP, BDNF, PSD-95, and VAChT, and the antioxidative potentials in the hippocampus. These results suggest the usefulness of DHA for treating stress disorders

Effect of chronic administration of arachidonic acid on the performance of learning and memory in aged rats

Background: Arachidonic acid (AA, C20:4, ω-6) is a ω-6 polyunsaturated fatty acid (PUFA) and plays diverse roles in cell signaling. Numerous reports on the effects of ω-3 PUFAs, such as docosahexaenoic acid (DHA, C22:6, ω-3) and eicosapentaenoic acid (EPA, C20:5, ω-3) on learning and memory impairments of rats are available, however, the role of AA on brain cognition is largely unknown. Objective: In this study, our aim was to investigate the effect of oral administration of AA on spatial memory-related learning ability in aged (100 weeks) male rats. Design: One group was per orally administered 240 mg/kg per day AA oil and the other group was administered the similar volume of control oil. Five weeks after the start of the administration, rats were tested with the partially baited eight-arm radial maze to evaluate two types of spatial memory-related learning ability displayed by reference memory errors (RMEs) and working memory errors (WMEs). Also, the time required to complete the task was recorded. The levels of lipid peroxide (LPO) and reactive oxygen species (ROS) were measured, as an indicator oxidative stress in the plasma and brain corticohippocampal brain tissues. Results: The scores of RMEs and WMEs, which are analogous to long-term and short-term memory, respectively, were not affected, however, the trial time was shorter in the AA-administered rats than that of the controls. AA also significantly increased the degree of oxidative stress both in the plasma and corticohippocampal brain tissues. Conclusions: Our results suggest that though AA deposition in the corticohippocampal tissues of senescent rats caused a faster performance activity, which is reminiscent to hyperactive behavior of animals, the spatial learning ability-related memory of the rats, however, was not improved