Homovanillic Research Articles

Serotonin and dopamine depletion in distinct brain regions may cause anxiety in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice as a model of early Parkinson's disease.

In this study, we aimed to evaluate the association of early anxious behavior with serotonin, dopamine, and their metabolites in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson's disease. Forty C57BL/6 male mice were randomly divided into the control group (n = 20) and the model group (n = 20). Mice in the model group were injected intraperitoneally with MPTP. The light-dark box (LDB) and elevated plus-maze were used to monitor anxious behavior. The association of early anxious behavior with neurotransmitters in the prefrontal cortex, hippocampus, and striatum was evaluated. In our murine model, MPTP induced a decreased level of 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the prefrontal cortex, hippocampus, and striatum (all P < 0.05); however, it only induced a decreased level of dopamine and its metabolite homovanillic acid (HVA) in the striatum (both P < 0.001), with a negative correlation in the hippocampus and a positive correlation in the cortex and striatum. In the LDB, 5-hydroxytryptamine levels in the cortex and dopamine and HVA levels in the striatum were negatively correlated with anxious behavior. Moreover, in the elevate plus-maze, 5-hydroxytryptamine and 5-HIAA in the cortex and dopamine and HVA in the striatum were positively correlated with the ratio of the time spent in open arms. In the murine model of early Parkinson's disease, the balance between dopamine and 5-hydroxytryptamine systems varied among brain regions. The depletion of 5-hydroxytryptamine in the cortex and dopamine in the striatum may be associated with anxiety behaviors in MPTP-treated mice.

Long-term prednisone treatment causes fungal microbiota dysbiosis and alters the ecological interaction between gut mycobiome and bacteriome in rats.

Glucocorticoids (GCs) are widely used in the treatment of immune-mediated diseases due to their anti-inflammatory and immunosuppressive effects. Prednisone is one of the most commonly used GCs. However, it is still unknown whether prednisone affects gut fungi in rats. Herein we investigated whether prednisone changed the composition of gut fungi and the interactions between gut mycobiome and bacteriome/fecal metabolome in rats. Twelve male Sprague-Dawley rats were randomly assigned to a control group and a prednisone group which received prednisone daily by gavage for 6 weeks. ITS2 rRNA gene sequencing of fecal samples was performed to identify differentially abundant gut fungi. The associations between gut mycobiome and bacterial genera/fecal metabolites obtained from our previously published study were explored by using Spearman correlation analysis. Our data showed that there were no changes in the richness of gut mycobiome in rats after prednisone treatment, but the diversity increased significantly. The relative abundance of genera Triangularia and Ciliophora decreased significantly. At the species level, the relative abundance of Aspergillus glabripes increased significantly, while Triangularia mangenotii and Ciliophora sp. decreased. In addition, prednisone altered the gut fungi-bacteria interkingdom interactions in rats after prednisone treatment. Additionally, the genus Triangularia was negatively correlated with m-aminobenzoic acid, but positively correlated with hydrocinnamic acid and valeric acid. Ciliophora was negatively correlated with phenylalanine and homovanillic acid, but positively correlated with 2-Phenylpropionate, hydrocinnamic acid, propionic acid, valeric acid, isobutyric acid, and isovaleric acid. In conclusion, long-term prednisone treatment caused fungal microbiota dysbiosis and might alter the ecological interaction between gut mycobiome and bacteriome in rats.

Propofol protects rats against intra-cerebroventricular streptozotocin-induced cognitive dysfunction and neuronal damage.

Cognitive dysfunction is a severe issue of Alzheimer's disease. Thus, the present study was conducted to enumerate the protective effect of propofol (PPL) in rats against intra-cerebroventricular streptozotocin (STZ)-induced cognitive dysfunction and neuronal damage. The effect of PPL was investigated to evaluate behavioural changes in STZ-induced cognitive dysfunction in Wistar rats using Object Recognition Task (ORT) for nonspatial, Morris Water Maze (MWM) for spatial and locomotor activity. The effect of PPL was also investigated on acetylcholine (ACh) esterase (AChE) activity and oxidative stress markers, e.g., nitrite, malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). The level of pro-inflammatory cytokines, e.g., tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, was also studied in the PPL-treated group. The effect of PPL on the level of neurotransmitters, e.g., dopamine (DA), serotonin (5-HT), and norepinephrine (NE) and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) levels were also estimated in frozen hippocampal tissues by high-performance liquid chromatography. Histopathology analysis of neurons in the hippocampus of rats was performed using haematoxylin and eosin (H&E) staining. Propofol showed significant improvement in the spatial and nonspatial memory deficit of rats in the MWM test and ORT in rats. It also causes improvement in locomotor activity of rats by preserving ACh via inhibition of AChE. It also potentiates the expression of DA, 5-HT, and NE with a simultaneous reduction in the level of metabolites (DOPAC, HVA, and 5-HIAA). PPL showed a reduction of oxidative stress in rats by restoring the level of nitrite, SOD, MDA, and GSH near to normal. In the PPL-treated group, the level of TNF-α, IL-1β, and IL-6 was found reduced in a dose-dependent manner. In histopathology analysis of neurons in the hippocampus of the STZ rats, PPL causes dose-dependent reduction of pyknosis in the nucleus, which confirmed the protective effect of PPL. The present study demonstrated that PPL could significantly attenuate cognitive dysfunction and neuronal damage in STZ-induced rats.

Determination of Multiple Neurotransmitters through LC-MS/MS to Confirm the Therapeutic Effects of Althaea rosea Flower on TTX-Intoxicated Rats.

Tetrodotoxin (TTX) inhibits neurotransmission in animals, and there is no specific antidote. In clinical practice in China, Althaea rosea (A. rosea flower) extract has been used to treat TTX poisoning. In this work, the efficacy of the ethyl acetate fraction extract of A. rosea flower in treating TTX poisoning in rats was investigated. A high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine nine neurotransmitters in rat brain tissue, including γ-aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT), noradrenaline (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA), epinephrine (E), and tyramine (Tyn). The detoxifying effect of A. rosea flower was verified by comparing the changes in neurotransmitters' content in brain tissue before and after poisoning in rats. The assay was performed in multiple reaction monitoring mode. The quantification method was performed by plotting an internal-standard working curve with good linearity (R2 > 0.9941) and sensitivity. Analyte recoveries were 94.04-107.53% (RSD < 4.21%). Results indicated that the levels of 5-HT, DA, E, and NE in the brains of TTX-intoxicated rats decreased, whereas the levels of GABA, Tyn, and 5-HIAA showed an opposite trend, and HVA and DOPAC were not detected. The levels of all seven neurotransmitters returned to normal after the gavage administration of ethyl acetate extract of A. rosea flower to prove that the ethyl acetate extract of A. rosea flower had a therapeutic effect on TTX poisoning. The work provided new ideas for studies on TTX detoxification.

Benzoic-D5 acid as D2 receptor agonist in the treatment of rotenone induced Parkinson’s disease in mice

Parkinson's disease is a progressive neurological disorder that affects movement. It is caused by the degeneration of dopamine-producing neurons in the brain. There is no cure for Parkinson's disease, but there are treatments available that can help manage the symptoms. Medications such as levodopa, dopamine agonists and Amantadine (Amd) can help to increase dopamine levels in the brain. Sodium benzoate (Benzoic-D5) is used as preservative in foods due to its antimicrobial potential. Benzoic-D5 showed a pivotal role in ameliorating the symptoms of Parkinson’s disease (PkD) in animal model. The current study is designed to probe the anti-Parkinson potential of Benzoic-D5 in the rotenone (ROT)-induced PkD mice. Behavioral studies showed improvement in sensory-motor functions, and neuromuscular strength in wire hanging test, grip strength, vertical rod test, and swim test. Evaluation of biochemical markers suggested increase in catalase (CAT) and superoxide dismutase (SOD), but decreases in the malondialdehyde (MDA) activity. Dopamine, dihydroxyphenyl acetic acid (DOPAC), and homovanillic acid (HVA) levels were improved in Benzoic-D5-treated animals. Moreover, there were down regulation of pro-inflammatory markers like TNF-α, NF-Kβ, and up regulation of anti-inflammatory IL-4 in the RT-PCR analysis. In molecular docking Benzoic-D5 showed strong binding affinity with an active site of Dopamine D2 receptor. Afterwards, ADMET analysis points to the selected drug’s acceptable properties. Conclusively, in vivo, and in silico studies propose that Benzoic-D5 possesses potentials to ameliorate symptoms of PkD. Binding energy data of Benzoic-D5 (-6.2), shows promising results compared to ROT (-6.0), and Amd (5.8).

Repeated Low-Level Blast Exposure Alters Urinary and Serum Metabolites

Repeated exposure to low-level blast overpressures can produce biological changes and clinical sequelae that resemble mild traumatic brain injury (TBI). While recent efforts have revealed several protein biomarkers for axonal injury during repetitive blast exposure, this study aims to explore potential small molecule biomarkers of brain injury during repeated blast exposure. This study evaluated a panel of ten small molecule metabolites involved in neurotransmission, oxidative stress, and energy metabolism in the urine and serum of military personnel (n = 27) conducting breacher training with repeated exposure to low-level blasts. The metabolites were analyzed using HPLC—tandem mass spectrometry, and the Wilcoxon signed-rank test was used for statistical analysis to compare the levels of pre-blast and post-blast exposures. Urinary levels of homovanillic acid (p &lt; 0.0001), linoleic acid (p = 0.0030), glutamate (p = 0.0027), and serum N-acetylaspartic acid (p = 0.0006) were found to be significantly altered following repeated blast exposure. Homovanillic acid concentration decreased continuously with subsequent repeat exposure. These results suggest that repeated low-level blast exposures can produce measurable changes in urine and serum metabolites that may aid in identifying individuals at increased risk of sustaining a TBI. Larger clinical studies are needed to extend the generalizability of these findings.

ЭФФЕКТЫ ВОЗДЕЙСТВИЯ ХРОНИЧЕСКОЙ АЛКОГОЛИЗАЦИИ И ГИПОДИНАМИИ НА ПОКАЗАТЕЛИ ДОФАМИНЕРГИЧЕСКОЙ СИСТЕМЫ НЕКОТОРЫХ ОТДЕЛОВ ГОЛОВНОГО МОЗГА КРЫС

Purpose of work. To determine the nature of changes in the content of dopamine and its metabolites in the cerebral cortex, hypothalamus and cerebellum of rats with chronic alcohol intoxication (CAI) against the background of physical inactivity (PI). Material and methods. The experiments were carried out on outbred white male rats weighing 180-220 g. Modeling of PI was carried out by placing rats in individual cages-pencil cases, limiting their mobility, for periods of 14 and 28 days. To simulate CAI, the animals were provided with an ethanol solution as the only source of fluid for 14 and 28 days. Determination of the content of the components of the dopaminergic system (tyrosine, 3,4-dioxyphenylalanine, dopamine, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and norepinephrine) was carried out using ion-pair high-performance liquid chromatography. Results. PI for 14 days is accompanied by signs of activation of the dopaminergic system in the hypothalamus and cerebral cortex of rats. With CAI for a period of 28 days, there are signs of a decrease in the activity of the dopaminergic system in the cerebral cortex. The combined effect of PI and CAI for 14 and 28 days leads to an increase in dopamine turnover in the cerebral cortex of rats. Conclusions. With the combined effect of CAI and PI, the most pronounced changes are observed in the cerebral cortex and are accompanied on the 14th day by an increase in the levels of HVA and DOPAC, and on the 28th day by an increase in the concentration of HVA.

Characterization of Elimination Pathways and the Feasibility of Endogenous Metabolites as Biomarkers of Organic Anion Transporter 1/3 (Oat1/3) Inhibition in Cynomolgus Monkeys.

Organic anion transporters 1 and 3 (OAT1/3) occupy a key role in mediating renal elimination. Kynurenic acid (KYNA) was previously discovered as an effective endogenous biomarker to assess drug-drug interaction (DDI) for OAT inhibitors. Here, further in vitro and in vivo investigation was performed to characterize the elimination routes and feasibility of KYNA, along with other reported endogenous metabolites, as biomarkers of Oat1/3 inhibition in bile duct-cannulated (BDC) cynomolgus monkeys. Our results suggested KYNA is a substrate of OAT1/3 and OAT2, but not OCT2, MATE1/2K, or NTCP, and it shares comparable affinities between OAT1 and OAT3. Renal and biliary excretions, and plasma concentration-time profiles of KYNA, pyridoxic acid (PDA), homovanillic acid (HVA), and coproporphyrin I (CP-I), were assessed in BDC monkeys dosed with either probenecid (PROB) at 100 mg/kg or the control vehicle. Renal excretion of KYNA, PDA, and HVA was determined to be the major elimination route. The maximum plasma concentration (Cmax) and AUC0-24h of KYNA were about 11.6 and 3.7-fold higher in the PROB group than in the vehicle group. Renal clearance (CLr) of KYNA decreased by 3.2-fold, but biliary clearance (CLbile) was not altered after PROB administration. A similar trend was observed for PDA and HVA. Interestingly, an elevation of plasma concentration and reduction of CP-I CLbile were observed after PROB treatment, which suggested inhibition of the CP-I Oatp-Mrp2 transport axis by PROB. Overall, our results indicated that KYNA could potentially facilitate early and reliable assessment of DDI liabilities of Oat inhibition in monkeys. Significance Statement This work reported renal excretion as the major elimination pathway for kynurenic acid, pyridoxic acid, and homovanillic acid. Administration of probenecid reduced renal clearance and increased plasma exposure of these biomarkers in monkeys, consistent with the observation in humans. These endogenous biomarkers discovered in monkeys could be potentially used to evaluate the clinical drug-drug interactions (DDIs) in the early phase of drug development.

Gender-Related Differences in the Relationship between Homovanillic Acid in the Cerebrospinal Fluid and Clinical Symptoms in Suicide Attempters

Introduction: Decreased dopaminergic activity – as reflected by lower levels of the major metabolite homovanillic acid (HVA) in cerebrospinal fluid (CSF) – may be involved in the pathophysiology of attempted suicide. An inverse association has also been found between dopaminergic activity and clinical symptoms of depression and anxiety in non-suicidal individuals. The aim of this study was to assess the relationship between CSF-HVA and clinical symptoms associated with an increased risk of suicide in individuals who attempted suicide. Methods: Ninety-five people (52 women; 43 men) who had recently attempted suicide received lumbar punctures to analyse levels of HVA in the CSF. They were also evaluated with the Comprehensive Psychopathological Rating Scale, from which scores on the Montgomery-Åsberg Depression Rating Scale (MADRS), the Brief Scale of Anxiety (BSA), and an item on suicidal thoughts were analysed. Results: Among female participants, CSF-HVA was significantly and negatively correlated with BSA total scores, after adjusting for covariates (beta = −0.442, p = 0.002), but not with scores on the MADRS or suicidal thought item. No significant correlations were observed between CSF-HVA and symptoms among male participants. Conclusion: Our findings suggest that lower dopaminergic activity may be associated with clinical symptoms of anxiety among women who have recently attempted suicide.

Perioperative hypertension and anesthetic management in patients undergoing resection of neuroblastoma.

Neuroblastoma is the most common extracranial pediatric tumor, accounting for 5-8% of all childhood cancers. Neuroblastomas arise from catecholamine-secreting neural crest cells and their metabolites, vanillylmandelic acid and homovanillic acid, that are readily detected in urine. Although rarely seen in clinical practice, case reports exist documenting severe intraoperative hypertension. However, data on the incidence of intraoperative hypertension are lacking. This report is a single-center retrospective review of patients with neuroblastoma who underwent surgical resection (n = 102) at Boston Children's Hospital from July 1, 2012 to February 28, 2021. Significant intraoperative hypertension was defined as maximum systolic blood pressure greater than 95th percentile +12 mmHg based on normative blood pressure data. Statistical analysis was performed using Fisher's exact test, Wilcoxon rank-sum test, and logistic regression. The overall incidence of intraoperative hypertension was 13% (n = 13/102). Higher American Society of Anesthesiologists (ASA) physical status was associated with intraoperative hypertension. Antihypertensive medications were administered intraoperatively in 9% of cases (n = 9), and the use was significantly associated with intraoperative hypertension. Of patients with preoperative urine catecholamine data (n = 82), all 10 patients who had intraoperative hypertension were noted to have elevated preoperative urine catecholamines. Intraoperative hypertension was not associated with postoperative hypertension, postoperative hypotension, or increased intensive care unit length of stay. Intraoperative hypertension in patients with neuroblastoma remains a relatively uncommon occurrence; however, it does occur at a frequency higher than previously described. While intraoperative hypertension is associated with an increased use of antihypertensive medications in the operating room, it is not associated with adverse perioperative outcomes.

Voltammetric Detection of Vanillylmandelic Acid and Homovanillic Acid Using Urea-Derivative-Modified Graphite Electrode

Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are diagnostic markers of neuroblastoma. The purpose of this study was to understand the reason for the discrimination of structural analogues (VMA and HVA) onto a graphite electrode coated with an electrochemically oxidized urea derivative. Density functional theory calculations (DFT), FTIR spectroscopic measurements, and electrochemical impedance spectroscopic measurements were used in this work. Density functional theory calculations (DFT) were used to identify the most suitable binding sites of the urea derivative and to describe possible differences in its interaction with the studied analytes. The FTIR measurement indicated the enhancement and disappearance of NH vibrations on graphite and platinum surfaces, respectively, that could be connected to a different orientation and thus provide accessibility of the urea moiety for the discrimination of carboxylates. Additionally, the higher the basicity of the anion, the stronger the hydrogen-bonding interaction with -NH-groups of the urea moiety: VMA (pKb = 10.6, KAds = (5.18 ± 1.95) × 105) and HVA (pKb = 9.6, KAds = (4.78 ± 1.58) × 104). The differential pulse voltammetric method was applied to detect VMA and HVA as individual species and interferents. As individual analytes, both HVA and VMA can be detected at a concentration of 1.99 × 10-5 M (RSD ≤ 0.28, recovery 110-115%).

Abstract 2199: Novel urinary marker for diagnosis and prognosis of neuroblastoma

Abstract Background and Aim: Urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA) concentrations are widely used for diagnosis of neuroblastomas, which are catecholamine-secreting tumors. As recent advances in mass spectrometry have facilitated the measurement of metabolites present at extremely low concentrations, urinary metabolites with better diagnostic or prognostic utility for detection of neuroblastomas could be identified. This study utilized quantitative analyses using liquid chromatography-mass spectrometry (LC-MS) to evaluate the diagnostic and prognostic performance of a novel biomarker candidate: 3-methoxytyramine sulfate [3-MTS]. Materials and Methods: The concentrations of the three urinary metabolites (HVA, VMA, and 3-MTS) in urine samples of 41 patients with primary neuroblastoma and urine samples of 155 control participants were measured using LC-MS. The cut-off values for these metabolites were the mean + 2 standard deviation values of the control. Linear discriminant analysis was used to evaluate the association of urinary marker candidates with unfavorable risk factors such as the International Neuroblastoma Pathology Classification and MYCN amplification. Results: The sensitivity and specificity were as follows: 3-MTS 90.2%, 94.2%; HVA 87.8%, 96.1%; VMA 87.8%, 96.1%; VMA or HVA+3-MTS 97.6%, 92.3%; HVA+VMA 87.8%, 94.8%; respectively. 3-MTS could differentiate between the cases with favorable and unfavorable histology (AUC =0.950). 3-MTS+VMA differentiated between the cases with MYCN amplification and nonamplification (AUC=0.952). Conclusions: 3-MTS might be a useful urine marker for both diagnosis and prognosis of neuroblastoma. Citation Format: Akinari Hinoki, Hizuru Amano, Hiroo Uchida, Atsushi Narita, Shun Kumano, Mayumi Abe, Minoru Sakairi, Chiyoe Shirota, Wataru Sumida, Satoshi Makita, Yoshiyuki Takahashi, Tsuyoshi Osawa. Novel urinary marker for diagnosis and prognosis of neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2199.

Optimising urinary catecholamine metabolite diagnostics for neuroblastoma.

The analysis of urinary catecholamine metabolites is a cornerstone of neuroblastoma diagnostics. Currently, there is no consensus regarding the sampling method, and variable combinations of catecholamine metabolites are being used. We investigated if spot urine samples can be reliably used for analysis of a panel of catecholamine metabolites for the diagnosis of neuroblastoma. Twenty-four-hour urine or spot urine samples were collected from patients with and without neuroblastoma at diagnosis. Homovanillic acid (HVA), vanillylmandelic acid (VMA), dopamine, 3-methoxytyramine, norepinephrine, normetanephrine, epinephrine and metanephrine were measured by high-performance liquid chromatography coupled with fluorescence detection (HPLC-FD) and/or ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC-MS/MS). Catecholamine metabolite levels were measured in urine samples of 400 neuroblastoma patients (24-hour urine, n = 234; spot urine, n = 166) and 571 controls (all spot urine). Excretion levels of catecholamine metabolites and the diagnostic sensitivity for each metabolite were similar in 24-hour urine and spot urine samples (p > .08 and >.27 for all metabolites). The area under the receiver-operating-characteristic curve (AUC) of the panel containing all eight catecholamine metabolites was significantly higher compared to that of only HVA and VMA (AUC = 0.952 vs. 0.920, p = .02). No differences were observed in metabolite levels between the two analysis methods. Catecholamine metabolites in spot urine and 24-hour urine resulted in similar diagnostic sensitivities. The Catecholamine Working Group recommends the implementation of spot urine as standard of care. The panel of eight catecholamine metabolites has superior diagnostic accuracy over VMA and HVA.

Simultaneous electrochemical determination of the tumour biomarkers homovanillic acid and vanillylmandelic acid using a modified pencil graphite electrode

This study describes the fabrication of an electrochemical sensor for the simultaneous detection of the tumour biomarkers homovanillic acid (HVA) and vanillylmandelic acid (VMA). The electrooxidation of HVA and VMA were studied at a pencil graphite electrode (PGE) modified with an electropolymer of 4- Aminosalicylic acid (ASA). Cyclic voltammetric (CV) studies of HVA and VMA on PGE and poly-ASA modified PGE (PASA-PGE) showed that simultaneous resolution of these analytes was possible only on PASA-PGE. The differential pulse voltammetric (DPV) response of HVA and VMA on PASA-PGE was found to be linear in a concentration range of 3.00 μM- 61.40 μM and 0.50 μM − 15.35 μM with a respective lower detection limit (LOD) of 1.82 μM and 0.28 μM. This is the first work reporting the electrochemical quantification of HVA and VMA simultaneously on PGE and was analytically applied for the determination of these analytes from human urine samples.

Metal organic framework-based tricolor fluorescence imprinted sensor for rapid intelligent detection of homovanillic acid

Homovanillic acid (HVA) is one of the main metabolites of catecholamines in the body. Abnormal levels of HVA in urine and serum are associated with neuroblastoma and Parkinson's disease. Herein, a smartphone-assisted tricolor fluorescence imprinted sensor was proposed with one-pot synthesis strategy for the intelligent determination of HVA in serum and urine. In this study, luminescent metal–organic framework was used as reference probe, while green-emitting CdTe and red-emitting CdTe were used as response probes. With increasing HVA concentration, the green-emitting CdTe and red-emitting CdTe fluorescence were gradually quenched, while the blue fluorescence of metal–organic framework remained stability. The tricolor fluorescence imprinted sensor extends the color variations range for visual detection with dynamic detection range (0.05–180 µM). The fluorescence imprinted sensor exhibits a lower detection limit of 15 nM and rapid response within 2 min. Interestingly, a portable smart sensing platform was designed by integrating the tricolor fluorescence imprinted polymer and a smartphone assisted device to achieve on-site accurate analysis HVA with a detection limit of 34 nM. The sensing platform was applied to in situ monitoring of HVA in serum and urine with satisfactory results, providing a new method for visual intelligent detection of HVA.

Correlations between cerebrospinal fluid homovanillic acid and dopamine transporter SPECT in degenerative parkinsonian syndromes

Both cerebrospinal fluid (CSF) homovanillic acid (HVA) and striatal dopamine transporter (DAT) binding on single-photon emission computed tomography (SPECT) reflect nigrostriatal dopaminergic function, but studies on the relationship between the two have been limited. It is also unknown whether the reported variance in striatal DAT binding among diseases reflects the pathophysiology or characteristics of the subjects. We included 70 patients with Parkinson’s disease (PD), 12 with progressive supranuclear palsy (PSP), 12 with multiple system atrophy, six with corticobasal syndrome, and nine with Alzheimer’s disease as disease control, who underwent both CSF analysis and 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-ioflupane) SPECT. We evaluated the correlation between CSF HVA concentration and the specific binding ratio (SBR) of striatal DAT binding. We also compared the SBR for each diagnosis, controlling for CSF HVA concentration. The correlations between the two were significant in patients with PD (r = 0.34, p = 0.004) and PSP (r = 0.77, p = 0.004). The mean SBR value was the lowest in patients with PSP and was significantly lower in patients with PSP than in those with PD (p = 0.037) after adjusting for CSF HVA concentration. Our study demonstrates that striatal DAT binding correlates with CSF HVA concentration in both PD and PSP, and striatal DAT reduction would be more advanced in PSP than in PD at an equivalent dopamine level. Striatal DAT binding may correlate with dopamine levels in the brain. The pathophysiology of each diagnosis may explain this difference.

The relation between electroconvulsive therapy and dopamine

IntroductionThe use of electroconvulsive therapy (ECT) as a treatment for psychotic disorders is well-documented and effective. Despite the fact that ECT is often used, the precise neurobiological mechanisms supporting its effectiveness are still incompletely understood. Over the pastyears, extensive research on primates, rodents, and humans has begun to clarify the effects of electroconvulsive seizures (ECS) and ECT on neurotransmission systems such the dopaminergic system.ObjectivesThe aim of this paper is to search evidence in the literature regarding the effects of ECT on the dopamine system.MethodsIn order to write this article, we searched for information in the most important scientific articles from the Google Scholar and Pubmed databases regarding the effects of ECT on the dopaminergic system.ResultsECT and electroconvulsive shock are linked to enhanced dopamine release and dopamine receptor modification. Human studies show that ECT activates the dopamine system. In a study by Rudorfer et al., it was discovered that ECT increased the amount of homovanillic acid (HVA), a marker of dopamine turnover, in the cerebrospinal fluid (CRF). One important study indicates that monkeys given a brief clinical course of ECT (six sessions only) exhibit significant changes in dopaminergic presynaptic neurotransmission, with baseline function returning to quadratic (‘inverted U’ shape) by six weeks of the last ECT treatment. According to single-unit electrophysiological methods, repeated electroconvulsive shock to rats causes a subsensitivity of dopamine autoreceptors in the substantia nigra. Since effects identical to those reported with repeated treatment were also detected when a single electroconvulsive shock was followed by an acceptable treatment-free interval, this decreased sensitivity is time-dependent.ConclusionsThe results support the idea that ECT boosts the dopamine system and can be an effective strategy in the management of psychotic disorders.Disclosure of InterestNone Declared

Reduced homovanillic acid, SDF-1α and SCGF-β levels in cerebrospinal fluid are related to depressive states in systemic lupus erythematosus.

This study aimed to seek a new method of evaluation and surrogate markers for diffuse neuropsychiatric SLE (NPSLE). We enrolled 44 patients with SLE between 2017 and 2020 who fulfilled at least one of three specific inclusion criteria: high disease activity, abnormal findings (cerebrospinal fluid [CSF] examination, brain MRI, or electroencephalography), or history of neuropsychiatric illness. Psychiatric symptom rating scales (PSYRATS) were evaluated retrospectively. The primary end point was the PSYRATS positivity rate in SLE patients who had not been diagnosed with diffuse NPSLE. Based on the 1999 ACR classifications, 7 out of the 44 patients evaluated using PSYRATS had been diagnosed with diffuse NPSLE. PSYRATS positivity was seen in 13 out of 37 SLE patients (35.1%) who had not been diagnosed with diffuse NPSLE, and all these patients were positive for Montgomery-Åsberg Depression Rating Scale (MADRS), an indicator of depression state in PSYRATS. Additionally, in the 20 SLE patients exhibiting depression symptoms who were MADRS-positive, CSF concentrations of the neuroinflammatory markers homovanillic acid (HVA; P = 0.0400), stromal cell-derived factor-1α (SDF-1α; P = 0.0431) and stem cell growth factor-β (SCGF-1β; P = 0.0061) were significantly reduced compared with the 24 MADRS-negative SLE patients, and the levels of HVA, SDF-1α and SCGF-1β correlated with one another (P < 0.05). Many patients with active SLE have subclinical depression, and MADRS evaluation of neuropsychiatric symptoms is useful for detecting them. Additionally, the decrease in CSF levels of HVA, SDF-1 α and SCGF-1β reflects the same pathology, and these may serve as surrogate markers.

Food restriction and hyperactivity induce changes in corticolimbic brain dopamine and serotonin levels in female rats

Compelling data support altered dopamine (DA) and serotonin (5-HT) signaling in anorexia nervosa (AN). However, their exact role in the etiopathogenesis of AN has yet to be elucidated. Here, we evaluated the corticolimbic brain levels of DA and 5-HT in the induction and recovery phases of the activity-based anorexia (ABA) model of AN. We exposed female rats to the ABA paradigm and measured the levels of DA, 5-HT, the metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and the dopaminergic type 2 (D2) receptors density in feeding- and reward-implicated brain regions (i.e., cerebral cortex, Cx; prefrontal cortex, PFC; caudate putamen, CPu; nucleus accumbens, NAcc; amygdala, Amy; hypothalamus, Hyp; hippocampus, Hipp). DA levels were significantly increased in the Cx, PFC and NAcc, while 5-HT was significantly enhanced in the NAcc and Hipp of ABA rats. Following recovery, DA was still elevated in the NAcc, while 5-HT was increased in the Hyp of recovered ABA rats. DA and 5-HT turnover were impaired at both ABA induction and recovery. D2 receptors density was increased in the NAcc shell. These results provide further proof of the impairment of the dopaminergic and serotoninergic systems in the brain of ABA rats and support the knowledge of the involvement of these two important neurotransmitter systems in the development and progression of AN. Thus, providing new insights on the corticolimbic regions involved in the monoamine dysregulations in the ABA model of AN.

Analysis of neurotransmitters validates the importance of the dopaminergic system in autism spectrum disorder.

The reasons behind the cardinal symptoms of communication deficits and repetitive, stereotyped behaviors that characterize autism spectrum disorder (ASD) remain unknown. The dopamine (DA) system, which regulates motor activity, goal-directed behaviors, and reward function, is believed to play a crucial role in ASD, although the exact mechanism is still unclear. Investigations have shown an association of the dopamine receptorD4 (DRD4) with various neurobehavioral disorders. We analyzed the association between ASD and four DRD4 genetic polymorphisms, 5' flanking 120-bp duplication (rs4646984), rs1800955 in the promoter, exon 1 12bp duplication (rs4646983), and exon 3 48bp repeats. We also examined plasma DA and its metabolite levels, DRD4 mRNA expression, and correlations of the studied polymorphisms with these parameters by case-control comparative analyses. The expression of DA transporter (DAT), which is important in regulating the circulating DA level, was also evaluated. A significantly higher occurrence of rs1800955 "T/TT" was observed in the probands. ASD traits were affected by rs1800955 "T" and the higher repeat alleles of the exon 3 48bp repeats, rs4646983 and rs4646984. ASD probands exhibited lower DA and norepinephrine levels together with higher homovanillic acid levels than the control subjects. DAT and DRD4 mRNA expression were down-regulated in the probands, especially in the presence of DAT rs3836790 "6R" and rs27072 "CC" and DRD4 rs4646984 higher repeat allele and rs1800955 "T". This pioneering investigation revealed a positive correlation between genetic variants, hypodopaminergic state, and impairment in socio-emotional and communication reciprocity in Indian subjects with ASD, warranting further in-depth analysis.