Effects of CI-926 (3-[4-[4-(3-methylphenyl)-1-piperazinyl] butyl]-2,-4-imidazolidinedione), an antihypertensive agent, on rat brain catecholamine and serotonin turnover

The effects of the antihypertensive drug CI-926 on rat brain norepinephrine (NE), dopamine (DA), and serotonin (5-HT) turnover and its in vitro affinity for several receptors were investigated. CI-926 (3-30 mg/kg intraperitoneally, i.p.) caused a dose-dependent increase in the rate of brain stem NE synthesis and increased the decline in NE after inhibition of its synthesis by alpha-methyl-p-tyrosine. These findings indicated that CI-926 increased brain NE turnover, probably as a compensatory response to central adrenoceptor blockade based on its nanomolar affinity for alpha 1-adrenoceptors and micromolar affinity for alpha 2-adrenoceptors. CI-926 also increased the rate of DA synthesis and DA metabolite levels; this indicates an increase in DA turnover. The latter effect of CI-926 is attributed to a compensatory response to DA-2 receptor blockade because no affinity for DA-1 relative to DA-2 receptors was found and the effect was antagonized by the DA agonist pergolide. CI-926 decreased brain 5-HT turnover, as indicated by reduced concentrations of the 5-HT metabolite 5-hydroxyindoleacetic acid and a reduced rate of 5-HT synthesis, effects characteristic of centrally acting 5-HT agonists. Based on its affinity for 5-HT-1A receptors versus 5-HT-1B and 5-HT-2, the decrease in 5-HT synthesis and release is interpreted as evidence of 5-HT-1A receptor activation. These findings indicate that besides peripheral alpha 1-adrenergic blockade, an interference of CI-926 with central adrenergic and serotoninergic neurotransmission may contribute in part to an explanation of its antihypertensive properties.     

Myriocin, a serine palmitoyltransferase inhibitor, alters regional brain neurotransmitter levels without concurrent inhibition of the brain sphingolipid biosynthesis in mice

Myriocin is a specific serine palmitoyltransferase (SPT) inhibitor whose effect on the brain is unknown. Brain amine metabolism and sphingolipid biosynthesis were studied in mice treated intraperitoneally with 0, 0.1, 0.3 or 1 mg/kg per day of myriocin for 5 days. Regional concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT, serotonin), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE), were determined. Sphinganine (Sa) and sphingosine (So) concentrations and SPT activity in brain and liver were used to evaluate the impact of myriocin on sphingolipid biosynthesis. Myriocin treatment increased DA in striatum and hippocampus and reduced it in cortex. NE concentration decreased in cerebellum and 5-HT levels were reduced in cortex and in medulla oblongata. Changes in ratios for DOPAC/DA and HVA/DA were observed in hippocampus, cortex and midbrain. Brain Sa, So and SPT activity remained unchanged, whereas Sa and SPT activity decreased in liver. Results showed that myriocin may alter the levels and metabolism of brain amines and this effect is not related with inhibition of sphingolipid biosynthesis in the nervous system.     

对氨基水杨酸钠对氯化锰染毒大鼠脑单胺递质的影响

本文报道了对氨基水杨酸钠(PAS-Na)对氯化锰腹腔注射染毒大鼠脑单胺递质水平的影响。PAS-Na能使锰染毒所降低了的脑多巴胺(DA)水平逆转;锰使脑去甲肾上腺素(NE)含量增加,染毒后以PAS-Na治疗则使之进一步升高;锰染毒和染毒后治疗组的5-羟色胺(5-HT)及5-羟吲哚醋酸(5-HIAA)的变化与DA相似,但PAS-Na使5-HT、5-HIAA水平升高的幅度大都较NE和DA的要小,提示5-HT能神经元对PAS-Na治疗作用的敏感性低于儿茶酚胺(CA)能神经元。     

A TRH analog (DN-1417). Effects on the levels of monoamines and the metabolites in the various brain regions in rats

The effects of a TRH (thyrotropin-releasing hormone) analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate), on the levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and the metabolites in the various brain regions of rats were determined by means of high performance liquid chromatography with electrochemical detection. DN-1417 (20 mg/kg, i.p.) produced marked decreases in the levels of NE, DA and 5-HT, especially in the nucleus accumbens, striatum and hypothalamus. The maximum effect was observed at 15 min after the administration. DA metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, increased significantly in the nucleus accumbens, striatum and hypothalamus, whereas 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid remained unchanged. 3-Methoxytyramine increased significantly in the nucleus accumbens and striatum. Two week chronic administration of DN-1417 (20 mg/kg, i.p.) increased the levels of DA and NE in the nucleus accumbens and DA in the striatum. These results suggest that DN-1417 stimulates the turnover of the cerebral monoamines, especially the release of DA from the nucleus accumbens and striatum in the mesolimbic and nigro-striatal DAergic systems.     

Subclinical effects of groundwater contaminants. IV. Effects of repeated oral exposure to combinations of benzene and toluene on regional brain monoamine metabolism in mice

Benzene and toluene are known neurotoxicants that may interact in vivo. The effect of combined treatment with benzene and toluene on the endogenous concentrations of the catecholamines norepinephrine (NE) and dopamine (DA), the catecholamine metabolites vanillylmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the indoleamine serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), were investigated in six discrete brain regions of CD-1 mice. Groups of male, adult mice were continuously exposed to benzene (166 mg/l), toluene (80 and 325 mg/l), and combinations of benzene + toluene (80 or 325 mg/l) in drinking water for 4 weeks. Benzene produced increases of NE in the hypothalamus, cortex, midbrain and medulla oblongata, DA in the hypothalamus and corpus striatum, and 5-HT in all dissected brain regions except cerebellum. Elevated levels of various monoamine metabolites were also observed in these brain areas. Toluene ingestion alone also significantly increased the concentrations of NE, DA, 5-HT, and their metabolites in several brain regions. Mice given the combined treatments exhibited raised regional neurochemical levels when compared to the untreated controls. Increased concentrations of biogenic amine metabolites in several brain regions were greater in the combined exposures of benzene and toluene than when either chemical was used alone. The findings were different from those observed on immune parameters using similar treatment protocols, where simultaneous exposure to toluene prevented the immunotoxic effects of benzene.     

Association between the levels of biogenic amines and superoxide anion production in brain regions of rats after subchronic exposure to TCDD

The effects of TCDD on the distribution of biogenic amines and production of superoxide anion (SA) in different brain regions of rats have been studied after subchronic exposure. Groups of females Sprague-Dawley rats were administered daily dose of 46ng TCDD/(kgday) (treated groups), or the vehicle used to dissolve TCDD (control group), for 90 days. The rats were sacrificed at the end of the exposure period and their brains were dissected into different regions including, hippocampus (H), cerebral cortex (Cc), cerebellum (C), and brain stem (Bs). The levels of different biogenic amines and some of their metabolites, including, norepinephrine (NE), dopamine (DA), 3,4-dihydroxy phenyl acetic acid (DOPAC), 4-hydroxy-3-methoxy-phenyl acetic acid (HVA), 5-hydroxy tryptamine (5-HT), and 5-hydroxy indole 3-acetic acid (5-HIAA), were determined in those brain regions, using a high performance liquid chromatography (HPLC) system with an electrochemical detector. SA production was also determined in those regions, using the cytochrome c reduction method. Results of analyses indicate significant increases in the levels of DA, NE and DOPAC in H, NE and HVA in Cc, NE and DA in Bs and NE in C. SA production was significantly increased in H and Cc, but not in Bs or C. The results also indicated strong correlations between DA and DOPAC, and SA and NE in all of the brain regions, and also between SA and 5-HT/HIAA in H and Cc. These results may indicate the contribution of biogenic amines, especially NE and 5-HT/HIAA to SA overproduction in some brain regions and may also indicate the potential of long term neurotoxic effects of those biogenic amines, in response to subchronic exposure to TCDD.     

Influence of formamidines on biogenic amine levels in rat brain and plasma

Biogenic amine levels in samples of whole brain and plasma following treatment of rats with chlordimeform (CDF), its two N-demethyl metabolites (DMC and DDC), p-chloroamphetamine (PCA), and harmaline were separated by high performance liquid chromatography equipped with fluorescence or electrochemical detection systems. At 1 hr following s.c. injection, CDF (200 mg/kg) caused a reduction in levels of norepinephrine (NE), 5-hydroxytryptamine (5-HT), and tyramine (TRM), an increase in dopamine (DA), and no change in levels of beta-phenethylamine (PEA) in samples of whole rat brain, whereas DMC (100 mg/kg) and DDC (25 mg/kg) effected reductions of brain levels of NE, 5-HT, TRM, and PEA with no change in DA. The effect of DMC (100 mg/kg) on NE and DA levels in brain was followed periodically for 24 hr. Following a significant decrease at 1 hr, NE levels increased to a maximum at 12 hr and remained higher than controls throughout the remainder of the 24 hr test period. DA levels increased during the initial 12 hr and remained significantly higher than controls for the remaining 12 hr. The influence of s.c. vs i.p. administration of DMC (100 mg/kg) on brain amine levels was examined. Intraperitoneal treatment generally resulted in lower amine levels in DMC and vehicle treated animals. Differences in treatment effects were similar for all amines except for 5-HT in which s.c. injection produced a slight reduction, while i.p. injection resulted in a two-fold increase.(ABSTRACT TRUNCATED AT 250 WORDS)     

利血平和帕吉林对大鼠脑单胺递质含量的联合作用

大鼠ip利血平2mg/kg后1-24h,NE,DA,5-HT均显著下降(p<0.05-p<0.001),5-HIAA则显著升高(p<0.001)。ip帕吉林60mg/kg后1-24h,NE,DA,5-HT均显著升高(p<0.01-p<0.001),5-HIAA则在1-2h内显著下降(p<0.01),4-24h无明显变化。同时使用两药时,对鼠脑NE和DA的影响均呈拮抗作用,对5-HT仅表现帕吉林的作用。帕吉林对利血平化鼠的NE,DA无影响,但可使5-HT升至正常水平;利血平对帕吉林化鼠递质的变化无影响。两药合用对递质的影响表现为拮抗或单一作用,未见递质翻转现象。     

Testosterone manipulations: effects on ranacide aggression and brain monoamines in the adult female rat.

The effect of testosterone propionate on ranacide (frog-killing) behavior and brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) levels was determined in 40 female Wistar rats. Adult rats were screened for frog killing behavior on the basis of a single 30 min testing session. Aggressors were defined as animals which attacked or killed during this session while nonaggressors failed to do so. Using either aggressors or nonaggressors, testosterone and sesame oil equally increased aggresive behavior as measured in a second 30 min testing session. Biochemical analyses indicated that testosterone treated animals had significantly higher brain NE and NE/5-HT levels. Aggressors, testosterone or sesame treated had higher NE/5-HT ratios. Whole-brain levels of DA and 5-HT and the DA/5-HT ratios were unaffected. It is concluded that the elicitation of ranacide in the adult female rat is not androgen dependent nor is this behavior functionally related to the observed differences in brain noradrenergic/serotonergic levels. This study provides additional evidence that ranacide is a type of predatory aggression and yet presents data which may be at variance with the classic monoaminergic theory of aggressive behaviors.     

Effects of piracetam on retention and biogenic amine turnover in albino rats.

The chronic effects of orally administered 2-pyrrolidone acetamide (piracetam) on one-trial, passive avoidance task were studied in albino rats. The effects on the contents of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in the brain and on the levels of their metabolites both in the brain and urine were also assessed. Significant improvement was observed in the retention ability compared with saline-administered controls. The contents of NE, DA, and 5-HT and their metabolites in the brain were significantly decreased after piracetam administration. The urinary metabolite levels were also significantly decreased except total 3-methoxy-4-hydroxyphenyl glycol (MHPG). These data indicate that piracetam causes an overall decrease in the turnover of central monoamines. Thus, the results of this study implicate the involvement of NE, DA, and 5-HT systems in learning and memory processes. Piracetam did not exert any GABAergic effect as shown by the absence of change in the brain GABA levels.     

Effects of pentylenetetrazol and trimethadione on feline brain monoamine metabolism

The effects of pentylenetetrazol on behavioral excitation and brain monoamine metabolism were compared by monitoring the EEG and assaying feline cerebrospinal fluid (CSF) for monoamine metabolites. After a non-convulsant dose of pentylenetetrazol, neither the concentrations of the 5-hydroxytryptamine (5-HT) metabolite, 5-hydroxyindoleacetic acid (5-HIAA), nor the dopamine(DA) metabolite, homovanillic acid (HVA), were altered in CSF if the rectal temperature of the cat was maintained. After a convulsant dose there was an increase in 5-HIAA and HVA levels. The norepinephrine (NE) metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), was also increased, but returned to control within 3 hr, while 5-HIAA and HVA levels were elevated for 24 hr. Trimethadione produced a transient decrease in HVA levels. When the convulsions, but not EEG excitation, are prevented by trimethadione pretreatment, brain monoamine metabolism is increased. Plasma tryptophan levels decreased after convulsant doses of pentylenetetrazol. Pentylenetetrazol was not detectable in plasma or CSF 24 hr after injection, while CSF 5-HIAA and HVA levels were still increased. These data show that pentylenetetrazol directly increases brain NE, DA and 5-HT metabolism while causing EEG excitatory changes, an effect which may precede convulsions.     

Correlative changes of serotonin and catecholamines with pharmacokinetic alterations of imipramine in rat brain

Rats were given i.p. imipramine (20 mg/kg), acutely or chronically, and the levels of serotonin (5-HT), norepinephrine (NE), dopamine (DA) and their metabolites in the brain at different times were compared with the concentrations of imipramine and desipramine. The levels of 5-HT, DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain did not appear to be affected by quantitative alterations in the concentrations of imipramine and desipramine. The level of 5-hydroxyindole acetic acid (5-HIAA) was reduced and the level of 3-methoxy-4-hydroxyphenylglycol (MHPG) tended to decrease 3 h after imipramine administration in acutely treated rats. The reduced level of 5-HIAA was maintained during the chronic treatment with imipramine, whereas the MHPG level increased and the NE level decreased. The decrease in 5-HIAA depended on the concentration of imipramine in the brain, whereas the changes in the levels of NE and MHPG appeared to be caused by desipramine. The present studies show that pharmacokinetic variations of imipramine in the brain might correlate with the altered levels of 5-HIAA, NE and MHPG.     

Potentiating effect of lithium chloride on aggressive behavior induced in mice by nialamide plus L-DOPA and by clonidine.

Effects of acute administration of LiCl on aggressive behavior and alterations in brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) contents induced by nialamide plus L-DOPA and by clonidine were examined in mice. Effects of LiCl on turnover and metabolism of brain NE were also investigated. LiCl potentiated the aggressiveness induced by both nialamide plus L-DOPA and by clonidine. Increase in levels of brain NE, DA and 5-HT by nialamide plus L-DOPA was not affected by LiCl. The potentiating effect of LiCl on clonidine aggression was not observed in mice pretreated with disulfiram. Although LiCl did not alter the steady state levels of brain NE, DA and 5-HT, it increased the turnover of NE and decreased the content of endogenous normetanephrine. These results favour the assumption that lithium reduces the ability of nerve terminal vesicles to store NE leading to an increased turnover and decreased concentration of NE at receptor sites.     

Changes of serotonin and catecholamines are related to pharmacokinetic alterations of clomipramine in rat brain.

When rats received a single i.p. injection of clomipramine (20 mg/kg), clomipramine and desmethylclomipramine were rapidly distributed into the brain and their concentrations were markedly higher in the brain than in the serum, while the concentration of the metabolite in the brain was much lower than that of clomipramine. Chronic administration of clomipramine gradually increased the concentrations of the metabolite in both serum and brain, but did not significantly change those of clomipramine. The levels of serotonin (5-HT), norepinephrine (NE), dopamine (DA) and their metabolites in the brain were compared with the concentrations of clomipramine and desmethylclomipramine at different times. The levels of 5-HT, NE, DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain did not appear to be affected by changes in the concentrations of the drug and metabolite. The level of 5-hydroxyindole acetic acid (5-HIAA) was reduced following clomipramine injection and the reduced level was maintained during chronic treatment. Chronic treatment for more than 7 days increased the 3-methoxy-4-hydroxyphenylglycol (MHPG) level with no alteration of NE level. This elevation appeared to be induced by desmethylclomipramine.     

Pharmacological studies on Y-8894 (VI). The effect on monoamine uptake and turnover in mouse brain

The effect of Y-8894 (+/-) 2-[[o-(2-thenyl)phenoxy]methyl] morpholine maleate, which has been shown to improve experimentally induced learning and memory deficits, on cerebral monoamine uptake and turnover was studied in the mouse. The following results were obtained: 1) It inhibited in vitro norepinephrine (NE) uptake to the mouse cerebral synaptosomal fractions about 800 and 1250 times more potently than it did those of dopamine (DA) and serotonin (5-HT), respectively. 2) It dose-dependently inhibited in vivo NE uptake, but not DA or 5-HT uptake. 3) It reduced the accumulation of the NE metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), increased that of the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and had no effect on that of the DA metabolite, homovanillic acid (HVA). These effects were compared with those of imipramine, calcium hopantenate (Ca-hopantenate) and dihydroergotoxine. Y-8894 appeared to act by stimulating the noradrenergic receptor, and it acts to a lesser extent by blocking the serotonergic receptor in the brain.     

Synthetic melanocyte stimulating hormone release-inhibiting factor (MIF). Part III: effect of L-prolyl-N-methyl-D-leucyl-glycinamide and MIF on biogenic amine turnover.

The effect of the factor that inhibits the release of melanocyte stimulating hormone (MSH), i.e., L-prolyl-L-leucyl-glycinamide (MIF), and L-prolyl-N-methyl-D-leucyl-glycinamide, an analog, on brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) turnover was examined in rats. The analog (40 mg/kg i.p.), in a fashion similar to MIF (40 and 5 mg/kg i.p.), increased brain DA turnover; only MIF (40 mg/kg i.p.) increased endogenous DA levels. The analog (40 and 5 mg/kg i.p.) decreased brain NE turnover; MIF at the same doses was ineffective. Neither MIF nor the analog affected rat brain 5-HT turnover or the 5-HTP-induced behavioural syndrome in the mouse. These results indicate that the analog, like MIF, exerts effects on central catecholamine turnover. The different biochemical profile of the analog compared to MIF may be importance with regard to potential clinical use in the treatment of Parkinson's disease and depression.     

Selective depleting effect of syrosingopine on brain catecholamine levels with relation to morphine analgesia in the rat.

Reserpine was the most potent, rescinnamine the next and syrosingopine the weakest in the depleting effects on brain amines of rauwolfia alkaloids. After syrosingopine, brain dopamine (DA) was decreased to a smaller degree and with a shorter duration as compared with norepinephrine (NE) and serotonin (5-HT), whereas reserpine elicited a marked and long lasting reduction in these amines. Accordingly, syrosingopine induced a depletion of brain NE and 5-HT without alteration in brain DA content 2-4 days after administration. Repeated administrations of syrosingopine, 2 mg/kg daily for 2 or 4 days, resulted in similar alterations in brain amine levels. This selective depleting effect of syrosingopine on brain amines was potentiated by combined treatment with disulfiram or fusaric acid, a dopamine beta-hydroxylase inhibitor. Under the condition of selective depletion of brain amines induced by repeated administrations of syrosingopine, 2 mg/kg daily for 2 days, the analgesic action of morphine was not affected, whereas reserpine and tetrabenazine antagonized morphine analgesia, concomitant with inducing a depletion of all brain amines. The results suggest that brain DA may be more important than brain NE or 5-HT with regard to the mechanisms by which morpine produces analgesia.     

Effects of RS-2232, a potential antidepressant, on the levels of monoamines, precursor amino acids and their related metabolites in mouse brain

The effects of RS-2232, a new antidepressant, on the levels of monoamines, precursor amino acids and their related metabolites in mouse brain were investigated and compared with some clinically effective antidepressants. RS-2232 (3, 10 and 30 mg/kg, p.o.) increased the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) dose-dependently, 60 min after administration. Tyrosine (TYR) levels were not changed, but tryptophan (TRP) was significantly increased by 20% at 30 mg/kg of the compound. On the other hand, DA metabolites such as 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were significantly reduced at all doses. 5-Hydroxyindoleacetic acid (5-HIAA), a 5-HT metabolite, was decreased by 32% at 10 mg/kg. These changes caused by RS-2232 administration were similar to those of the classical inhibitor of monoamine oxidase (MAO), isocarboxazid (ISO), but rather different from those of imipramine (IMP) and mianserin (MIA). RS-2232 and ISO antagonized against reserpine (2 mg/kg, s.c.)-induced changes in the contents of monoamines and their metabolites. Furthermore, time-course experiments clearly showed that increase in the levels of monoamines by 10 mg/kg of RS-2232 was restored to the control levels within a few hours. These results suggest that RS-2232 has reversible MAO inhibiting properties in vivo in mouse brain.     

Alteration of monoamine concentrations in the brain of medaka, Oryzias latipes, exposed to tributyltin

We measured the concentrations of monoamines in the brain of Japanese medaka, Oryzias latipes, exposed to tributyltin (TBT). Fish were exposed to 0, 1, 5, 25, or 125 microg g(-1) of TBT via the diet for 21 days. After the administration period, six males and six females in each treatment group were dissected and their brains were collected. The following monoamines were analyzed: dopamine (DA), norepinephrine (NE), epinephrine (E), and 5-hydroxytryptamine (5-HT). The metabolites of DA, 3,4-dihydroxyphenylacetic acid and homovanilic acid, and the metabolite of 5-HT, 5-hydroxyindolacetic acid were also analyzed. The concentration of DA in the brain of male medaka and the concentrations of 5-HT and NE in the female brains were significantly decreased by exposure to 125 microg TBT g(-1). The concentrations of 5-HT and NE in males and of DA in females were slightly decreased by 125 micrg g(-1) of TBT, although the differences were not statistically significant. The present study demonstrates that TBT alters monoamine concentrations in the brain of medaka.     

The influence of orally administered docosahexaenoic acid on monoamine neurotransmitter,nerve growth factor,and brain-derived neurotrophic factor in aged mice

In this study we attempt to investigate the new role of docosahexaenoic acid (DHA) supplementation on cognitive ability in aged mice. Kunming-line mice were treated with DHA (200, 400?mg/kg body weight/day) for 30 successive days. The cognitive ability of mice was assessed by learning and memory behavioral test; the levels of DHA were assessed by capillary gas chromatography; the levels of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) were assessed by high-performance liquid chromatography; the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) proteins were assessed by the enzyme-linked immunosorbent assay method. The results showed the cognitive ability of mice were significantly different between the DHA-treated groups and the aged group, and orally administered DHA can increase the levels of DA, NE and 5-HT, the content of BDNF and NGF proteins in hippocampus, frontal cortex and striatum tissues. In addition, aged-related changes in phospholipid DHA content were seen. Decreases in DHA were mostly corrected by DHA supplementation. These novel data suggest that DHA supplementation can improve the cognitive dysfunction due to aging by increasing the levels of BDNF and NGF protein and the levels of DA, NE, 5-HT to some extent. We speculate that the mechanism of DHA on cognitive ability may have a beneficial effect on signaling networks through modulation of monoamine neurotransmitters and neurotrophic factors in brain aging.