Homovanillic Acid Concentrations Research Articles

Abnormal neurotransmitter metabolite levels in Alzheimer patients with a delirium

Delirium is a complex neuropsychiatric syndrome with an acute onset and fluctuating course. Several studies have suggested the presence of disturbed cholinergic, dopaminergic and serotonergic pathways in delirium as well as in Alzheimer's disease. Abnormal concentrations of amino acids and of neurotransmitter metabolites have been found in plasma, platelets and cerebrospinal fluid of AD patients, and in plasma and CSF of patients with a delirium. The aim of this study was to investigate amino acid and neurotransmitter metabolite levels in plasma of AD patients with a concurrent delirium. In a case-control study of patients suffering from Alzheimer's disease (AD) with concurrent delirium, we investigated the contribution of delirium to some biochemical parameters in blood. We compared plasma amino acid and neurotransmitter metabolite levels of 17 delirious AD patients with those of 17 age- and gender-matched non-delirious AD patients and 29 age- and gender-matched controls. Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) levels were higher in delirious AD patients than in controls, but only HVA concentrations were higher in delirious AD patients than in non-delirious AD patients. Our findings suggest that central dopaminergic and serotonergic turnover are increased in AD patients with delirium and that the high dopaminergic turnover might reflect the consequences of delirium.

Brain monoaminergic neurotransmission parameters in weanling rats after perinatal exposure to methylmercury and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153)

The individual and joint effects of methylmercury (MeHg; 1 mg/kg body weight/day, GD7–PND7) and PCB153 (20 mg/kg body weight/day, GD10–GD16), administered orally to rat dams, were explored in 21-day-old rat offspring brain in terms of monoamine oxidase B (MAO-B) activity and regional content of dopamine (DA), serotonin (5-HT), 5-hydroxy-indole-3-acetic acid (5-HIAA) and homovanillic acid (HVA). Neither treatment altered MAO-B in striatum, hippocampus, cerebellum and cerebral cortex of female pups. In males the cerebellum displayed a significantly reduced enzyme activity (25–45%) following all treatments. Concerning biogenic amines, 5-HT levels were decreased by 30–50% in the cerebral cortex of males and females by PCB153 alone and combined with MeHg, without changes in 5-HIAA and dopaminergic endpoints. In cerebellum of all pups, MeHg enhanced 5-HIAA levels, whereas PCB153, either alone or combined with MeHg, did not affect this endpoint. In striatum, PCB153 reduced the content of DA, HVA and 5-HIAA (respective control values: 2–3; 60–80; 8–10 ng/mg protein) to a similar extent when administered alone or together with MeHg (20–40%). Perinatal exposure to MeHg and/or PCB153 results in regionally and/or gender-specific alterations in the central dopaminergic and serotonergic systems at weaning. The combined treatment with MeHg and PCB153 does not exacerbate the neurochemical effects of the individual compounds.

Iron in the Brain

After completing this article, readers should be able to: 1. Describe the role of iron in proteins involved in neuronal and glial energy metabolism, myelin production, and monoamine neurotransmitter metabolism. 2. Indicate the neonates who are at risk for iron deficiency. 3. Explain how iron deficiency affects the biochemistry, structure, signaling molecules, and electrophysiology of the hippocampus. 4. Describe the primary causes of iron overload in the neonate. 5. Explain why the preterm infant is at particular risk for iron deficiency. This article is designed to acquaint readers with the role of iron in early brain development. Several important principles that govern the effects of nutrients on the immature brain are discussed, followed by an explanation of the roles of iron during development. Because the developing brain is sensitive to iron overload as well as iron deficiency, both are discussed in the context of human studies and in model systems. The first guiding principle of nutrient-brain interactions during development is the concept of timing, dose, and duration. (1) The positive or negative effects of any nutrient depend on which brain regions or processes are developing at the time that nutrient status is altered and the requirements of those regions for the nutrient during that time of development. Generally, the more rapidly an area is developing, the more vulnerable it is. Dependence on specific nutrients during phases of rapid proliferation or differentiation results in the second principle, a regionalization of brain effects during periods of nutrient deficiency. In the case of iron deficiency, certain brain areas that are dependent on iron for proper development are more vulnerable than areas that are less dependent on iron. Additionally, these same brain areas are likely to be more vulnerable at certain time points than at others. To exert a maximal effect on regional brain development, the timing of iron …

A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index

Variation in brain monoaminergic activity is heritable and modulates risk of alcoholism and other addictions, as well as food intake and energy expenditure. Monoamine oxidase A deaminates the monoamine neurotransmitters serotonin, dopamine (DA), and noradrenaline. The monoamine oxidase A (MAOA) gene (Xp11.5) contains a length polymorphism in its promoter region (MAOA-LPR) that putatively affects transcriptional efficiency. Our goals were to test (1) whether MAOA-LPR contributes to interindividual variation in monoamine activity, assessed using levels of cerebrospinal fluid (CSF) monoamine metabolites; and (2) whether MAOA-LPR genotype influences alcoholism and/or body mass index (BMI). Male, unrelated criminal alcoholics (N=278) and controls (N=227) were collected from a homogeneous Finnish source population. CSF concentration of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were available from 208 participants. Single allele, hemizygous genotypes were grouped according to inferred effect of the MAOA alleles on transcriptional activity. MAOA-LPR genotypes had a significant effect on CSF HVA concentration (P=0.01) but explained only 3% of the total variance. There was a detectable but nonsignificant genotype effect on 5-HIAA and no effects on MHPG. Specifically, the genotype conferring high MAOA activity was associated with lower HVA levels in both alcoholics and controls, a finding that persisted after accounting for the potential confounds of alcoholism, BMI, height, and smoking. MAOA-LPR genotype predicted BMI (P<0.005), with the high-activity genotype being associated with lower BMI. MAOA-LPR genotypes were not associated with alcoholism or related psychiatric phenotypes in this data set. Our results suggest that MAOA-LPR allelic variation modulates DA turnover in the CNS, but does so in a manner contrary to our prior expectation that alleles conferring high activity would predict higher HVA levels in CSF. Our results are consistent with an emerging literature that suggests greater complexity in how variation in MAOA expression alters monoaminergic function. Finally, our work suggests that MAOA may be involved in the regulation of BMI. Independent samples are necessary to confirm this preliminary finding.

Catecholamine Response to Methamphetamine is Related to Glucocorticoid Levels but not to Pleasurable Subjective Response

Corticosteroids may modulate addiction. We previously described subjective, physiological, and endocrine effects of 0.5 mg/kg of intravenous methamphetamine after augmenting cortisol level with hydrocortisone or blocking cortisol response with the corticosteroid synthesis inhibitor metyrapone in a double-blind, balanced crossover study. Although the pharmacologic manipulations produced the expected hormonal changes, pleasurable subjective effects of methamphetamine were unchanged. Metyrapone was followed by frequent premature ventricular complexes (PVCs) in two subjects during methamphetamine administration. In order to better understand these results, we examined changes in two plasma catecholamine metabolites, homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), and their relationship to the previously reported hormonal changes and physiological and subjective responses. Plasma from 10 methamphetamine subjects from the earlier study was assayed for HVA and MHPG by high performance liquid chromatography. HVA levels were greater after hydrocortisone or metyrapone pretreatment compared to placebo, and MHPG levels were greater after metyrapone pretreatment. Hydrocortisone pretreatment diminished HVA and MHPG increases after methamphetamine (perhaps explaining the lack of expected increase in pleasurable effects), but metyrapone did not. HVA and MHPG concentrations were not correlated with pleasurable drug effects but were inversely related to reports of "Bad Drug Effect." Increases in MHPG and DHEA concentrations were positively correlated. Metyrapone pre-treated subjects with PVCs had lower HVA and MHPG concentrations. Raising cortisol concentration and blocking cortisol synthesis did not produce opposite effects, perhaps because of metyrapone's effect on the hypothalamic-pituitary-adrenal axis, its stress-like effects, and its effects on neurosteroids.

Influence of the catechol- O-methyltransferase Val108/158Met polymorphism on the plasma concentration of catecholamine metabolites and on clinical features in type I bipolar disorder—A preliminary report

Background The activity of catechol- O-methyltransferase (COMT) may be related to psychosis susceptibility. The Val108/158Met polymorphism of the COMT gene influences its enzymatic activity and may result in altered concentrations of monoamine metabolites and different clinical responses of patients to pharmacological treatments. Methods We examined in a sample of 42 bipolar patients if the Val108/158Met polymorphism influences: (a) the presence of psychosis in type I bipolar patients; (b) the blood plasma concentration of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), which are metabolites of dopamine and noradrenaline respectively and (c) the severity of the clinical characteristics of these patients and their response to pharmacological treatment. Results No significant associations were found between the studied COMT genotypes and the studied parameters. However, a non-significant aggregation of bipolar patients presenting with psychosis was found in the homozygous Val-Val group. Clinical improvement was found to significantly correlate with the levels of plasma MHPG prior to treatment. Moreover, a significant difference was found between the standard deviations of the concentrations of HVA in the three genotypes, but not in their mean values. Significant associations were not detected between COMT polymorphisms and the initial severity of the disorder, or the clinical response to pharmacological treatment. Limitations The size of the studied sample is somewhat small and comparisons have been made with a previously studied control group. Conclusions The Val108/158Met polymorphism does not appear to be a crucial determinant in type I bipolar disorder.

Subacute administration of tributyltin chloride modulates neurotransmitters and their metabolites in discrete brain regions of maternal mice and their F1 offspring

Tributyltin (TBT) compounds have been used as anti-fouling agents and the central nervous system is one of its target organs. TBT-induced modulations of neurotransmitters in the brains of adult mice have been reported. However, little is known about the developmental neurotoxicity of TBT. In this study, we evaluated the effects of TBT on neurotransmitters and their metabolites in discrete brain regions of female ICR mice and their offspring. Pregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15 or 50 ppm in water or 125 ppm in food. Male offspring were sacrificed at one, two and three weeks after birth. The concentrations of norepinephrine, dopamine (DA), dihydoxyphenylacetic acid, homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in different brain regions by HPLC. All offspring from the 125 ppm group died immediately after birth. A significant decrease in the body weight of the TBT-treated F1 groups compared to the control group was observed in the first week. Significant increases compared to the controls were observed for the DA concentration in the striatum of the 50 ppm F1 group, and for the HVA concentration in the cerebrum and the 5-HT concentration in the medulla oblongata of the 15 and 50 ppm F1 groups in the third week. At three weeks of age, the neurotransmitters and their metabolites may be useful indexes for developmental neurotoxicity. For the dams, a significant decrease in the 5-HT concentration was observed in the cerebellum, medulla, midbrain and striatum of the 125 ppm group compared to the control group. A significant decrease in the 5-HIAA concentration was also observed in the cerebellum, midbrain and striatum of the dams in the 125 ppm group compared to the control. TBT may induce a decrease in the synthesis of 5-HT in the dams. The discrepancy between dams and offspring may be due to several factors such as age, dose, route, sex and pregnancy.

Cerebrospinal fluid kynurenic acid in male and female controls – Correlation with monoamine metabolites and influences of confounding factors

The concentrations of the tryptophan metabolite kynurenic acid (KYNA) and the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were determined in the cerebrospinal fluid (CSF) from 43 healthy volunteers (30 males and 13 females). Healthy female controls displayed higher CSF concentration of KYNA (1.91 nM ± 0.20) compared to healthy male controls (1.06 nM ± 0.07) and lower CSF levels of HMPG (39.2 nM ± 2.0 and 43.4 ± 1.2, respectively). CSF levels of HVA and 5-HIAA did not differ between females (181.3 nM ± 21.9 and 93.7 nM ± 11.4, respectively) and males (138.9 nM ± 12.6 and 74.8 nM ± 5.9, respectively). Positive intercorrelations were found between CSF KYNA, HVA and 5-HIAA while CSF content of HMPG did not correlate with KYNA or the other monoamine metabolites in CSF. A negative correlation was found between back length and CSF concentrations of KYNA, HVA and 5-HIAA and also between CSF KYNA levels and body height. The results of the present study suggest that concentrations of KYNA and the monoamine metabolites in CSF from healthy controls are dependent on gender and back length, which must be taken in consideration when analysing mixed groups of men and women. The higher KYNA concentration found in female controls compared to male might be attributed to a shorter back in women compared to men. Furthermore, these findings suggest that increased KYNA formation is associated with an increased dopamine and serotonin turnover.

Motor effects of buspirone: Relationship with dopamine and serotonin in the striatum.

To determine the effect of low and high doses of buspirone on motor activity and striatal monoamine metabolism in rats. Experimental study. The experiments were performed in the Department of Biochemistry, Karachi University from October to December 2003. Behavioral and neurochemical effects of agents were monitored acutely. Motor activity was scored in open field. Neurochemical estimations in the striatum were carried out by high performance liquid chromatography. Administration of buspirone at low (1 mg/kg) and high (10 mg/kg) doses increased latency to move in open field and decreased number of squares crossed. The agent injected at a dose of 1 mg/kg decreased dopamine concentration and increased the concentration of homovanillic acid. Increases of homovanillic acid were smaller at a dose of 1 mg/kg than 10 mg/kg. Changes in the levels of dihydroxyphenyl acetic acid were not significant. Administration of buspirone decreased 5-hydroxytryptamine metabolism at a dose of 1 mg/kg but not at a dose of 10 mg/kg. The present results provide neurochemical evidence that low but not high dose of buspirone preferentially stimulates somatodendritic 5-hydroxytryptamine-1A receptors resulting in a decrease in striatal serotonin metabolism. Low dose of buspirone could release dopaminergic neurons from inhibitory influence of serotonin and may be useful in reducing parkinsonian-like effects of traditional antipsychotics.

Effects of triadimefon on extracellular dopamine, DOPAC, HVA and 5-HIAA in adult rat striatum

Triadimefon has been shown to inhibit monoamine uptake, bind to the dopamine (DA) transporter, and stimulate dopamine efflux in rat brain tissue, in vitro. To determine whether these changes also occur in the intact animal and to study the reversibility of the effects observed, we used in vivo microdialysis to determine changes in the concentrations of DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) in the striatal dialysates from free moving adult rats after exposure to triadimefon 50, 100 and 200 mg/kg, i.p. Triadimefon induced a gradual dose- and time-dependent accumulation of extracellular DA accompanied by a small increase in the HVA and 5-HIAA concentrations. These changes were still present 24 h after treatment in the group treated with 200 mg/kg and had vanished 48 h after treatment. In contrast to the DA efflux induced by S(+)-amphetamine (2 mg/kg, i.p.), that induced by triadimefon was totally inhibited by the infusion of 10 −5 M tetrodotoxin (TTX), a voltage-gated Na + channel blocker, thus showing that the increase in extracellular DA induced by triadimefon was an action potential-dependent mechanism. GBR 12909 (10 mg/kg, i.p.), a dopamine uptake inhibitor, induced a gradual increase in striatal dopamine similar to that induced by triadimefon, whereas the effects on the acid metabolites were not exactly the same. The present results indicate that triadimefon acts in vivo as a DA transporter inhibitor and could also act on the serotoninergic system.

Relationship Between Interindividual Differences and Physiological Indexes of Acute Stress in Rats

We used in vivo microdialysis to examine interindividual differences in the effects of acute immobilization stress and diazepam treatment on monoamine turnover in the hippocampus of male rats as an index of stress. Immobilization significantly increased the concentrations of 3,4‐dihydroxyphenyl‐aceticacid (DOPAC), homovanillic acid (HVA), and 5‐hydroxyindoleacetic acid (5‐HIAA). This effect was attenuated by injection of diazepam, Interindividual differences in reactivity to stressors caused differential changes in different metabolic products of monoamines. In our study, stress‐induced changes in DOPAC levels were relatively great, and there was a similar change in the concentration of HVA. We conclude that at least 2 indexes of stress should be measured to take into account interindividual differences in the changes in stress indexes.

Computational Approach to the Rational Design of Molecularly Imprinted Polymers for Voltammetric Sensing of Homovanillic Acid

A methodology based on density functional theory calculations for the design of molecularly imprinted polymers (MIPs) is described. The method allows the rational choice of the most suitable monomer and polymerization solvent among a set of chemicals traditionally used in MIP formulations for the molecular imprinting of a given template. It is based on the comparison of the stabilization energies of the prepolymerization adducts between the template and different functional monomers. The effect of the polymerization solvent is included using the polarizable continuum model. A voltammetric sensor for homovanillic acid was constructed using different MIPs as recognition element, confirming that the solvent (toluene) and functional monomer (methacrylic acid) selected according to the theoretical predictions lead to the most efficient molecular recognition sensing phase. With the voltammetric sensor prepared using the MIP designed according to the theoretical predictions, a linear response for concentrations of homovanillic acid between 5 x 10(-8) and 1 x 10(-5) M can be obtained. The limit of detection is 7 x 10(-9) M. The selectivity obtained for homovanillic acid over other structurally related compounds buttresses the validity of this strategy of design.

Cerebrospinal Fluid Catecholamine Levels in Japanese Encephalitis Patients with Movement Disorders

Norepinephrine and dopamine have important role in movement disorders but their role in movement disorders associated with Japanese encephalitis (JE) has not been evaluated. Therefore, in the present study, cerebrospinal fluid (CSF) catecholamine levels and its metabolites in JE patients with movement disorders were compared with those without JE. CSF was collected by lumbar puncture and analyzed by HPLC-ED. Norepinephrine, dopamine and homovanillic acid concentrations were significantly (P<0.005) lower in JE patients compared to control groups. Low levels of catecholamines in JE associated movement disorders compared to idiopathic Parkinson's disease and other extrapyramidal symptoms may be due to severe structural damage to thalamus, basal ganglia and brainstem in JE patients as revealed by MRI findings.

Oestrogens Prevent Loss of Dopamine Transporter (DAT) and Vesicular Monoamine Transporter (VMAT2) in Substantia Nigra of 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine Mice

Previous results from our laboratory have shown that 17beta-oestradiol prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) striatal dopamine depletion. 17beta-oestradiol, oestriol and oestrone are the naturally occurring oestogens in humans. Using various dopamine markers, the present study investigated whether oestrone and oestriol such as 17beta-oestradiol have neuroprotective activity in MPTP-treated mice. Male mice were treated with 17beta-oestradiol, oestriol or oestrone for 5 days before and after MPTP administration, and were compared with nonlesioned mice receiving the same treatment. Striatal concentrations of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were assayed by high-performance liquid chromatography. Dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) specific binding were measured by autoradiography. DAT, VMAT2 and tyrosine hydroxylase mRNA levels were measured by in situ hybridisation. MPTP induced a loss of DAT and VMAT2 specific binding in the striatum and substantia nigra, as well as a decrease of VMAT2 mRNA in the substantia nigra. 17beta-oestradiol treatment prevented the loss of these dopaminergic markers, as well as striatal concentrations of dopamine, DOPAC and HVA. Mice receiving oestriol and oestrone showed catecholamine concentrations comparable to MPTP mice. Oestriol treatment had no effect on dopaminergic markers in MPTP mice whereas oestrone prevented striatal DAT loss and the decrease of VMAT2 mRNA in the substantia nigra. In nonlesioned mice, 17beta-oestradiol, oestriol or oestrone had no effect on all the dopaminergic markers investigated. In conclusion, a weak or a lack of effect of oestriol and oestrone was observed compared to 17beta-oestradiol in MPTP mice and none of these steroids had an effect in nonlesioned mice. A DAT and VMAT2 specific binding decrease after MPTP in the striatum and substantia nigra, as well as a decrease of substantia nigra VMAT2 mRNA, was observed and could be prevented by oestradiol.

An open study of risperidone liquid in the acute phase of schizophrenia

An open-label study was performed to investigate the clinical efficacy and mechanisms of risperidone liquid in ameliorating positive symptoms in the acute phase of schizophrenia. Eighty-eight patients (M/F: 50/38; age: 18-74 years;, mean +/- SD =32 +/- 16 years) meeting DSM-IV criteria for schizophrenia and treated with risperidone liquid (14 patients also used lorazepam) were evaluated with regard to their clinical improvement and extrapyramidal side effects using the positive and negative syndrome scale (PANSS) and the Simpson and Angus scale (SAS), while plasma concentrations of HVA and MHPG were analysed by HPLC-ECD before and 4 weeks after risperidone liquid administration. Patients showing a 50% or greater improvement in PANSS scores were defined as responders. An improvement in the PANSS scores related to excitement, hostility and poor impulse control was seen within 7 days after administration of risperidone liquid, and an improvement with regard to hallucinatory behaviour and uncooperativeness was seen within 14 days after its administration. Finally, 68% of patients were classified as responders 4 weeks after risperidone liquid administration. The scores of SAS were not changed after risperidone liquid administration. Pretreatment plasma homovanillic acid (HVA) levels in the responders (8.1 +/- 2.9 ng/ml) were higher than those in nonresponders (5.9 +/- 1.9 ng/ml). In addition, a negative correlation was seen between the changes in plasma HVA levels and the percentage of improvement in PANSS scores. On the other hand, there were no differences between pretreatment plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and those of nonresponders. These results suggest that risperidone liquid is effective and well tolerated for the treatment of acute phase schizophrenic patients, and that efficacy is related to its affects on dopaminergic activity, not noradrenergic activity.

The role of physicochemical properties of entacapone and tolcapone on their efficacy during local intrastriatal administration

Aqueous solubility, apparent partition coefficient (log P app) and catechol- O-methyltransferase (COMT, EC 2.1.1.6) inhibiting potency of entacapone and tolcapone were compared in vitro. Both drugs (at 10 and 100 μM) were also delivered directly into rat striatum via a microdialysis probe. Extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations were measured to evaluate the inhibition of striatal COMT in vivo. Although entacapone had 15-fold better aqueous solubility than tolcapone at pH 7.4, also tolcapone had sufficient aqueous solubility to remain in solution at 100 μM. The log P app of tolcapone was higher than that reported for entacapone in the pH range from 5.0 to 7.4. Entacapone and tolcapone inhibited equally rat striatal COMT in vitro with K i values of 1.86 and 2.50 nM, respectively. Both drugs had similar outflow from the microdialysis probe in vitro. Perfusion of 100 μM entacapone increased significantly extracellular DOPAC levels compared to the control group. Both entacapone and tolcapone (at 10 and 100 μM) decreased significantly HVA levels, but entacapone was significantly more effective than tolcapone at 100 μM. In conclusion, entacapone and tolcapone are equally potent COMT inhibitors against rat striatal COMT in vitro. After local intrastriatal administration, entacapone appeared to inhibit COMT faster and more effectively than the more lipophilic tolcapone. Thus, intrastriatal administration led to opposite results compared to those reported in the brain after systemic administration. The present results also suggest that the local distribution of entacapone and tolcapone differ when the drugs are delivered directly into the brain.

The protective role of dl-α-lipoic acid in biogenic amines catabolism triggered by Aβ amyloid vaccination in mice

The major pathological consequence of Alzheimer disease (AD) is accumulation of β-amyloid (Aβ) peptide fibrillar plaque in the brain and subsequent inflammatory reaction associated with the surrounding cells due to the presence of these aggregates. Inflammation is the major complication associated with Aβ peptide vaccination. Aβ peptide activated T-helper cells are shown to enhance the existing-inflammatory conditions in the brain and other organs of AD patients. Hence systematic studies on potential approaches that will prevent inflammation during the vaccination are highly desired. dl-α-Lipoic acid (LA), an antioxidant with known function as cofactor in mitochondrial dehydrogenase reactions, will be a good candidate to annul the oxidative damage due to vaccination triggered inflammation. For the first time, levels of principal neurotransmitters and their major metabolites in hippocampus and neocortex regions of brain are quantified to find out the level of inflammation. We have used high performance liquid chromatography with electro chemical detection (HPLC–EC) for monitoring neurotransmitter levels. We have shown a significant ( p < 0.05) reduction of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the systemic inflammation induced (SI), vaccinated (VA) and inflammation induced vaccinated (IV) mice. Nevertheless their metabolites such as 5-hydroxyindole acetic acid (5-HIAA) and homovanillic acid (HVA) are significantly ( p < 0.05) increased when compared with control. Interestingly, antioxidant LA treated mice with systemic inflammation (IL), vaccinated (VL) and inflammation induced vaccinated (IVL) mice exhibited enhanced level of 5-HT, DA and NE and the concentration of 5-HIAA and HVA gradually returned to normal. These results suggest a possible new way for monitoring and modifying the inflammation and thereby preventing Aβ vaccination mediated tissue damage.

Growth hormone-induced stimulation of swimming and feeding behaviour of rainbow trout is abolished by the D 1 dopamine antagonist SCH23390

The effects of GH on various types of behaviour in fish are well documented although the underlying mechanisms are not fully understood. In rainbow trout, an involvement of the brain dopaminergic system in mediating the behavioural effects of GH has been indicated, as GH can alter the brain dopaminergic activity. To further examine the role of the dopaminergic system in the mediation of GH effects on locomotion and foraging, GH- and sham-implanted juvenile rainbow trout were injected with the selective D 1 dopamine antagonist SCH23390 or vehicle. Swimming and feeding activity was then studied by direct observation. Brains were thereafter sampled and analysed for the content of serotonin, dopamine and their metabolites in the hypothalamus, optic tectum, cerebellum, telencephalon, and brain stem. GH increased swimming activity as well as feed intake, effects which were abolished by SCH23390. By itself, the antagonist did not affect behaviour, nor did it affect the brain monoamines. In contrast, treatment with GH, with or without SCH23390, decreased the content of the dopamine metabolite homovanillic acid (HVA) in the optic tectum and the cerebellum, as well as the serotonin content (5-HT) in the optic tectum. It is concluded that the D 1 dopamine receptor of the dopaminergic system appears to be of importance in the mediation of the effects of GH on behaviour.

Liquid chromatography-electrochemical detection for studying the effects of tetrahydrobiopterin on monoamine neurotransmitters in rat striatum

Tetrahydrobiopterin (BH4) is an essential co-factor in the biosynthesis of monoamine neurotransmitters. A nano-Pt/Pd modified electrode as the electrochemical detector (ED) for high-performance liquid chromatography (HPLC) coupled with microdialysis sampling, is used to explore the effect of administration of BH4 on the monoamine neurotransmitters in the rat striatum. The researches demonstrate that the contents of dopamine (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) increase significantly with the administration of BH4. The pharmaceutical kinetics is carried out to research into the time course of BH4 effect on the concentration of monoamine neurotransmitters in rat striatum, which provides reliable data for pathology and pharmacology research on neuroscience.

Reduced Brain Delivery of Homovanillic Acid to Cerebrospinal Fluid During Human Aging

Markers of human brain dopamine metabolism are reported to decline with age. However, the cerebrospinal fluid (CSF) concentration of homovanillic acid (HVA), a major dopamine metabolite, is reported to not change or to increase in elderly individuals. To estimate the rate of delivery of HVA from the brain to CSF, taking into account the HVA concentration gradient in the spinal subarachnoid space and CSF flow. Homovanillic acid concentrations were measured in 5 serial 6-mL aliquots of CSF removed from the L3-4 or L4-5 interspaces of 7 healthy young (mean +/- SD age, 28.7 +/- 4.6 years) subjects and 7 healthy elderly (mean +/- SD age, 77.1 +/- 6.3 years) subjects. Cisterna magna HVA concentrations were estimated from the slopes of the HVA concentrations along the spinal subarachnoid space. The products of cisternal HVA concentrations and published values for CSF flow were used to estimate lower limits for brain delivery of HVA to CSF, according to the Fick principle. The mean +/- SD HVA concentration in the initial lumbar CSF sample in the young subjects, 116 +/- 66 pmol/mL, did not differ significantly from 140 +/- 86 pmol/mL in the elderly subjects. Estimated cisternal HVA concentrations equaled 704 and 640 pmol/mL, respectively, in the young and elderly subjects. Multiplying these concentrations by CSF flow rates of 591 and 294 mL/d, respectively, gave lower limits for rates of delivery of HVA from the brain to CSF. These rates equaled 416 and 175 nmol/d, respectively. A 50% decline in the lower limit for the rate of HVA delivery from the brain to CSF in elderly individuals is consistent with other evidence that brain dopaminergic neurotransmission declines with age.