Dopamine Concentrations Research Articles

Features оf Changes in the Level of Neurotransmitters and Markers of Neurodegeneration in the Brain of Rats with Experimental Parkinson’s Disease Against the Background of Course Therapy with Steroid Glycoalkaloids

Parkinson’s disease is a chronic neurodegenerative disease, one of the pathobiochemical manifestations of which is an imbalance of neurotransmitters in the brain. The aim of this work is to study the effect of glycoalkaloids on changes in the level of neurotransmitters and markers of brain neurodegeneration in rats with experimental Parkinson’s disease. Parkinson’s disease was modeled in animals by intracerebral administration of rotenone. The studied glycoalkaloids were administered orally at a dose of 0.06 mg / kg, a course of 28 days after pathology modeling. The study found that the use of the analyzed glycoalkaloids did not affect the concentration of dopamine and serotonin, and also significantly (p 0.05) reduced the level of ACh by 35.9% and increased the level of GABA by 55.1%, reduced the concentration of S100β protein by 68.6% and increased the level of BDNF by 52.4%.

Social isolation induces addictive behavior and increases release of dopamine in the <i>nucleus accumbens</i> in response to stimulation of the positive reinforcing zone

The study of the role of social isolation in the pathogenesis of addictive behavior disorders is an important medical and biological problem. Of particular importance are the limitations of social experience in ontogenesis. This work makes an attempt to find a connection between social isolation in ontogenesis and impulsive-compulsive behavior, as an indicator of the premorbid background for gaming and other forms of behavioral addictions. The mechanisms of addictive behavior in rats reared in isolation (IS) were investigated by analyzing the extracellular release of dopamine in response to stimulation of the positive reinforcing zone. Before the experiments, male rats were kept in individual cages from the 21st day of birth to the 90th day. To study elements of addictive behavior, a variant of the Iowa Gambling Task in a 3-arm maze and a method of developing compulsive overeating using intermittent consumption of high-calorie foods were used. To study compulsive behavior, a marble test was used against the background of withdrawal from a high-calorie diet. Surgeries were performed to implant electrodes into the ventral tegmental area (VTA) and the nucleus accumbens in rats exhibiting elements of addictive behavior in the 3-arm maze. These animals were then trained to respond to VTA self-stimulation. Dopamine release was recorded telemetrically in freely moving rats in response to electrical stimulation of the VTA self-stimulation zone. Fast scan cyclic voltammetry was used to determine changes in dopamine levels in the extracellular environment of the nucleus accumbens. IS entered less into the arm with a high degree of probability but with a low reward, and entered more in the arm with a low degree of probability, but with a high reward, which is associated with the appearance of impulsivity in behavior. In the model of compulsive overeating, the number of approaches to the feeder in IS increased, and against the background of withdrawal of high-calorie food, IS were more active in the marble test. In IS exhibiting elements of addictive behavior in the 3-arm maze, the content of extracellular dopamine in response to electrical stimulation of the VTA self-stimulation zones did not reveal any differences compared to the control group of rats with addictive behavior in the maze. At the same time, IS exhibiting elements of addictive behavior in the maze showed a more pronounced dopamine response to a complex stimulus: a conditioned signal used during maze learning light + VTA stimulation. Thus, rearing in the IS causes an increase in dopamine release in the nucleus accumbens in response to stimulation of the positive reinforcement area associated with addictive behaviors: impulsivity and compulsivity. A conclusion is drawn about the prospects of studying the extracellular release of dopamine and assesses addictive behavior disorders caused by limited social contacts in ontogenesis.

Changes in the content of dopamine, serotonin, their precurrents and derivatives in the prefrontal cortex of the brain of young male rats under chronic exposure to low-intense electromagnetic field

Changes in the content of dopamine, serotonin, their precurrents and derivatives in the prefrontal cortex of the brain of young male rats under chronic exposure to low-intense electromagnetic field

Fermented Gold Kiwi Improves Gastrointestinal Motility and Functional Constipation: An Animal Study and Human Randomized Clinical Test

Constipation is a functional disorder of the gastrointestinal system characterized by difficult bowel movements, infrequent defecation, reduced water content, and hard stools. This study aims to evaluate the preventive effects of fermented gold kiwis (FGK) on loperamide-induced constipation in rats and investigate its efficacy in improving constipation symptoms in human patients through a randomized clinical trial. In the animal study, FGK was administered orally at doses of 50, 125, and 250 mg/kg to constipated rats for two weeks, resulting in significant improvements in constipation parameters. FGK increased serum serotonin and acetylcholine levels and suppressed increases in serum dopamine concentration. FGK also upregulated mRNA expression of the serotonin-synthesizing receptors 5-HT3R and 5-HT4R and suppressed the expression of the dopamine 2-receptor (D2R) in the duodenum. Furthermore, FGK inhibited inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. In the clinical trials, the improvement in constipation symptoms was evaluated using the gastrointestinal symptom rating scale (GSRS). Clinical trial participants reported significant improvements in constipation symptoms after receiving FGK. These findings suggest that FGK effectively relieves constipation in both animals and humans, indicating its potential as an effective dietary supplement.

Effects of Prenatal Methcathinone Exposure on the Neurological Behavior of Adult Offspring.

Our previous research has shown that prenatal methcathinone exposure affects the neurodevelopment and neurobehavior of adolescent offspring, but the study on whether these findings continue into adulthood is limited. This study aims to explore the effects of prenatal methcathinone exposure on anxiety-like behavior, learning and memory abilities, as well as serum 5-hydroxytryptamine and dopamine concentrations in adult offspring. Pregnant rats were injected daily with methcathinone between the 7th and 20th days of gestation. The neurobehavioral performance of both male and female adult offspring rats was evaluated by neurobehavioral tests, including open-field tests, Morris water maze (MWM) tests, and novel object recognition (NOR) tests. The levels of 5-hydroxytryptamine and dopamine concentration in rat serum were detected by ELISA. Significant differences were found in the length of center distance and time of center duration in the open-field test, as well as the times of crossing the platform in the MWM test, between the prenatal methcathinone exposure group and the control group. Results of the NOR test showed that adult offspring rats exposed to methcathinone need more time to discriminate the novel object. No gender differences were detected in the neurobehavioral tests. The serum concentrations of 5-hydroxytryptamine and dopamine in rats exposed to methcathinone prenatally were lower than that in the control group, and the serum dopamine concentration was independent of gender in each group. Prenatal methcathinone exposure affects the neurological behavior in adult offspring, and 5-hydroxytryptamine and dopamine might be involved in the process.

High performance loose-structured membrane enabled by rapid co-deposition of dopamine and polyamide-amine for dye separation

Textile wastewater poses a significant environmental challenge that demands effective treatment. Membrane separation offers a promising solution, with high-flux tight ultrafiltration membranes recognized as an effective technology for dye separation. Polyamide amine (PAMAM), a dendritic macromolecule renowned for its regular structure, high monodispersity, excellent solubility, and tunable molecular weight, has emerged as a promising material for membrane fabrication. This study introduces a novel, eco-friendly, and time-efficient method for preparing polymer composite membranes through one-step co-deposition of dopamine (DA) and PAMAM, predominantly utilizing Michael addition and Schiff base reactions. The incorporation of ammine-rich PAMAM imparts ultra-high hydrophilicity to the membranes (contact angle of 38°), facilitating strong adhesion of water molecules to the membrane surface. The effects of co-deposition time and concentrations of DA and PAMAM on the separation performance of the resulting membranes were systematically investigated. Notably, the optimal membrane demonstrated a high water flux (126.1 L m-2h−1 bar−1), primarily due to the incorporation of PAMAM, which resulted in a looser selective separation layer. Furthermore, the membrane demonstrated excellent rejection of methyl blue (MB) at 98.9 % and low rejection os methyl orange (MO) at 13.2 %, making it well-suited for the selective separation of mixed dyes. Our approach offers a sustainable and technologically advanced solution for addressing resource recovery from textile wastewater.

Carbon dots modified hydrange-shaped ZnCo(OH)F used as a flexible electrode for sensitive detection of dopamine and uric acid

Dopamine (DA), widely recognized as the most prevalent catecholamine neurotransmitter in the brain, functions as a vital regulator of various physiological processes within the central nervous system. Meanwhile, uric acid (UA) serves as the terminal product of purine metabolism, and hyperuricemia emerges as a significant risk factor for gout, with a steep escalation in risk as blood uric acid levels surge. Consequently, monitoring the concentrations of DA and UA in biological fluids is crucial not only for the treatment of related disorders but also for enhancing disease prevention strategies. In this work, the blooming hydrangea shaped ZnCo(OH)F/carbon dots (CDs) composite was grown on carbon cloth (CC) substrate by a simple hydrothermal method, which was used as a flexible sensor for the detection of DA and UA. The unique open structure and morphologic adjustment strategy of ZnCo(OH)F/CDs/CC provided a large surface area and highly exposed active site. After screening the experimental variables that affect the sensor performance, the optimal ZnCo(OH)F/CDs/CC flexible electrode achieved individual and simultaneous detection for DA and UA in the concentration ranges of 1.0220.0µM and 1.0500.0µM, the detection limits (LOD) of DA and UA were 0.0129 and 0.044μM, respectively (S/N=3). In addition, the sensor exhibited good repeatability, stability and selectivity, realizing the detection of DA and UA in human serum with recovery rate of 95.20% 105.3%. Also, the density functional theory (DFT) calculations were used to explore the interaction between electrode material and detected substrate. A simple hydrothermal method was utilized to grow the ZnCo(OH)F/CDs composite onto the CC substrate. The presence of F− in ZnCo(OH)F can increase the charge mobility and improve the conductivity. ZnCo(OH)F/CDs/CC as flexible electrode material can determine DA and UA simultaneously in human serum with a satisfactory recovery rate. This flexible sensor has a broad application prospect in the manufacture of wearable devices.

Lanthanide coordination polymers as luminescent laccase mimics for ratiometric sensing of dopamine

Some metal ions, with inner enzyme-like catalytic activity, could be doped into lanthanide coordination polymers (Ln CPs) through coordination, which has been proved as a facile strategy to prepare the luminescent nanozymes. In this study, Cu-doped Ln CPs with laccase-mimic activity and double luminescence were rationally designed and synthesized by self-assembly of guanine monophosphate (GMP), 2-aminoterephthalic acid (ATA), Cu2+ and Tb3+ in buffer solution at room temperature. The obtained probes Tb/Cu-GMP/ATA CPs not only emitted green fluorescence of Tb3+ and blue fluorescence of ATA simultaneously under irradiation at the same wavelength, but also processed enhanced laccase-like activity for catalyzing the oxidation of phenolic substrates. Upon dopamine (DA), the probes catalyzed the oxidation of DA to polydopamine (PDA), which effectively quenched the fluorescence of Tb3+ due to the internal filtration effect. Based on this, a ratiometric fluorescent sensor for DA was constructed accordingly, and the corresponding fluorescence intensity ratio of Tb3+to ATA (F547/F427) was linearly correlated with the DA concentration in the range of 1 to 400 μM, with a detection limit of 0.44 μM. Besides, this sensor could be used to detect DA in human serum samples with good recovery, which results were highly consistent with that of HPLC method. The constituent and luminescence tunability, as well as the extraordinarily facile synthesis, made Ln CPs a potential platform for designing and preparing the integrated multifunctional probe for special target in sensing applications.

The participation of monoamines in the realization of vasopressin analgesic effects during electrical stimulation of paws in rats

BACKGROUND: Arginine vasopressin has been implicated in the modulation of stress and pain. The influence of a synthetic analogue of arginine vasopressin, 1-deamino-8-D-arginine-vasopressin, оn pain sensitivity, stress reactivity, levels of monoamines and brain neurotrophic factor in a model of paw electrical stimulation in rats has not been studied. AIM: The aim was to evaluate the effect of a synthetic vasopressin analog, 1-deamino-8-D-arginine-vasopressin, on pain sensitivity and the content of norepinephrine, serotonin, dopamine, brain neurotrophic factor in the parietal cortex and spinal cord in electrocutaneous paw stimulation test in rats. MATERIALS AND METHODS: The study was conducted on male Wistar rats who were injected with 1-deamino-8-D-arginine-vasopressin intranasally once a day for 5 days in small (single 20 ng, course 100 ng) and large doses (single 2 ug, course 10 ug). The content of brain neurotrophic factor in the parietal cortex and spinal cord, and corticosterone in blood serum were determined using enzyme immunoassay. The levels of norepinephrine, serotonin, dopamine and their metabolites in the brain were evaluated using high-performance liquid chromatography. RESULTS: 1-Deamino-8-D-arginine-vasopressin in different doses reduced pain sensitivity in rats, more pronounced when administered in large doses. The peptide in small doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid, a metabolite of serotonin; in the spinal cord, it reduced the content of 5-hydroxyindolacetic acid. 1-Deamino-8-D-arginine-vasopressin in high doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid; in the spinal cord ― reduced the content of serotonin and 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine; increased the levels of norepinephrine and homovanilic acid, a metabolite of dopamine. The peptide had no effect on corticosterone levels in the blood and brain neurotrophic factor levels in the brain in rats. CONCLUSIONS: The analgesic effects of 1-deamino-8-D-arginine-vasopressin were revealed with intranasal administration in different subendocrine doses. Regardless of the administered doses, dopamine and serotonin at the supraspinal level were involved in peptide-induced anesthesia; serotonin at the spinal cord level. More pronounced analgesia with the administration of 1-deamino-8-D-arginine-vasopressin in high doses was due to the additional involvement of dopamine and norepinephrine at the spinal cord level.

Dopamine internalization via Uptake2 and stimulation of intracellular D5-receptor-dependent calcium mobilization and CDP-diacylglycerol signaling

Dopamine stimulates CDP-diacylglycerol biosynthesis through D1-like receptors, particularly the D5 subtype most of which is intracellularly localized. CDP-diacylglycerol regulates phosphatidylinositol-4,5-bisphosphate-dependent signaling cascades by serving as obligatory substrate for phosphatidylinositol biosynthesis. Here, we used acute and organotypic brain tissues and cultured cells to explore the mechanism by which extracellular dopamine acts to modulate intracellular CDP-diacylglycerol. Dopamine stimulated CDP-diacylglycerol in organotypic and neural cells lacking the presynaptic dopamine transporter, and this action was selectively mimicked by D1-like receptor agonists SKF38393 and SKF83959. Dopaminergic CDP-diacylglycerol stimulation was blocked by decynium-22 which blocks Uptake2-like transporters and by anti-microtubule disrupters of cytoskeletal transport, suggesting transmembrane uptake and guided transport of the ligands to intracellular sites of CDP-diacylglycerol regulation. Fluorescent or radiolabeled dopamine was saturably transported into primary neurons or B35 neuroblastoma cells expressing the plasmamembrane monoamine transporter, PMAT. Microinjection of 10-nM final concentration of dopamine into human D5-receptor-transfected U2-OS cells rapidly and transiently increased cytosolic calcium concentrations by 316%, whereas non-D5-receptor-expressing U2-OS cells showed no response. Given that U2-OS cells natively express PMAT, bath application of 10 μM dopamine slowly increased cytosolic calcium in D5-expressing cells. These observations indicate that dopamine is actively transported by a PMAT-implicated Uptake2-like mechanism into postsynaptic-type dopaminoceptive cells where the monoamine stimulates its intracellular D5-type receptors to mobilize cytosolic calcium and promote CDP-diacylglycerol biosynthesis. This is probably the first demonstration of functional intracellular dopamine receptor coupling in neural tissue, thus challenging the conventional paradigm that postsynaptic dopamine uptake serves merely as a mechanism for deactivating spent or excessive synaptic transmitter.

Glia dysfunction in schizophrenia: evidence of possible therapeutic effects of nervonic acid in a preclinical model.

Neuroinflammation may inhibit oligodendrocyte and astrocyte differentiation, which causes demyelination and synaptic degeneration. The myelin component nervonic acid (NA) may improve demyelinating and neurodegenerative diseases. This study firstly explored relationships between glial cell dysfunction and demyelination or synaptic degeneration in schizophrenia patients, and secondly determined nervonic acid therapeutic effects in a preclinical schizophrenia model of mice. Plasma samples were collected from 18 male healthy controls and 18 male schizophrenic patients (diagnosed by DSM-V) at aged 18-55. Mouse brain samples were collected from a maternal immune activation (MIA) model of schizophrenia via injecting 5mg/kg polyinosinic-polycytidylic acid. Male mouse offspring (age 2.5months, n = 12) were treated by clozapine (15mg/kg/day) or fed 0.5% NA for 6weeks. Cytokine and dopamine (DA) concentrations, and glial phenotypes and myelin markers were measured in both human plasma and mouse brain samples. In patient plasma, increased proinflammatory cytokines were associated with reactive microglia (Iba-1) up-regulation, while decreased anti-inflammatory cytokines were related to microglia (CD206) downregulation. Decreased astrocyte marker (p11) concentrations were accompanied by reduced concentrations of oligodendrocyte and synaptic markers. However, NA and DA contents were increased. Compared with control mice, SZ-like behaviors appeared in MIA male mice. Changes in microglia and astrocytes markers, and cytokine concentrations in the frontal cortex were consistent with those observed in patients' plasma. Hippocampal oligodendrocyte and synaptic marker expression were also decreased. DA content and DA/metabolite (DAPOC) were increased in MIA mouse brains. Most of these changes were normalized by both clozapine and NA. Even though some NA effects were more pronounced than clozapine, only clozapine restored cytokine function. The data suggest a possible therapeutic route for schizophrenia patients.

Experimental study of preservation of probiotic lactic acid bacteria in freeze-dried yogurts

This article presents research results on the relationship between the survival rate of lactic acid bacteria and the content of neurotransmitters in freeze-dried yogurt and yogurt with the addition of 15% pumpkin puree as a cryoprotectant. The decrease (p < 0.05) in the survival rate of lactic acid bacteria up to 52% and a predominance of norepinephrine (660–680 pmol/g) was noted in yogurt without cryoprotectant. In yogurt containing pumpkin puree, the survival rate of lactic acid bacteria was 25–28% higher. The content of serotonin and dopamine in freeze-dried yogurt with puree increased (p < 0.05) to 120–130 and 350–360 pmol/g, respectively. The use of pumpkin puree affects the content of neurotransmitters and allows the preservation of lactic acid bacteria cells if a sufficiently high primary drying temperature is used. The higher primary drying temperature and the use of cryoprotectant results in decreased (p < 0.05) drying time, energy savings, and an average of 20% in carbon footprint.

Carbon cloth surface engineering for simultaneous detection of ascorbic acid, dopamine, and uric acid in fetal bovine serum

Carbon cloth (CC) was electrochemically activated using three electrochemical methods in different electrolytes. The gases released during the activation process etched the surface of the CC, thereby increasing its surface area of the activated CC (FCC). Moreover, functional groups such as oxygen-containing groups and N-doping have been introduced. The quantity and type of functional groups introduced during the activation process were related to the anions in the solution. FCC electrodes were used to construct electrochemical sensors for the simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA). The PFCC electrode activated by advanced cyclic voltammetry in (NH4)2HPO4 showed linear ranges for AA, DA, and UA concentrations of 0.1 to 2.1 mM, 0.5 to 11 µM, and 0.5 to 11 µM, respectively. The detection limits are 72.93, 0.22, and 0.42 µM, respectively. The good flexibility the PFCC electrode made it suitable for the preparation of flexible sensors. The simultaneous determination of AA, DA, and UA in fetal bovine serum showed a reliable recovery ratio. This study provides a simple and green approach for activating carbon cloth and constructing flexible electrochemical sensors with the potential to simultaneously detect AA, DA, and UA.

Preparation and adsorption application of PLA/GO/PDA nanofiber membrane

Abstract In this study, PLA(polylactic acid)/GO(graphene oxide)/DA(Dopamine) porous nanofiber membrane was prepared by electrospinning. L16(43) orthogonal experiment was designed to investigate the effects of reaction temperature, reaction time, and DA concentration on the adsorption performance of DA oxidized and self-polymerized on the fiber. Based on the characterization of scanning electron microscopy and the determination of the adsorption performance of the fiber membrane to MB(methylene blue dye), data visualization analysis, variance analysis, and F-test were conducted to determine the optimal process parameters: reaction temperature of 45 ℃, reaction time of 30 h, and DA concentration of 2 mg/ml. PLA/GO/PDA(Polydopamine) nanofiber was prepared and characterized under the optimal process parameters. The results showed that the average diameter of the PDA-loaded nanofiber increased from 737 nm to 996 nm, and a layer of PDA with a thickness of about 129 nm was loaded on the outer surface of the fiber, making the contact angle of the fiber membrane with 0° and becoming a hydrophilic material. In adsorption performance testing of MB, the PLA/GO/PDA nanofiber membrane prepared based on the PLA/GO/DA fiber membrane with an adsorption rate of 98.81 % in 24 h was superior to the PLA/GO/PDA nanofiber membrane prepared based on the PLA/GO fiber membrane.

Black and white truffles as a source of neuroactive biogenic amines

This study reports the first data about content of serotonin, histamine, and dopamine in black and white truffles fruiting body based on UHPLC-ESI-QqQ-MS/MS. Here we have demonstrated that black (Tuber macrosporum) and white (T. magnatum) truffles are a source of biogenic amines. Also, we demonstrated the absence of correlation between the quality of truffles and the content of biogenic amines.

Physiological and metabolic effects of short-term dopamine reduction in healthy horses using a tyrosine hydroxylase inhibitor (alpha-methyl-para-tyrosine)

Alpha-methyl-para-tyrosine (AMPT) is a reversible inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This study aimed to determine whether AMPT could reduce dopamine concentrations in horses. Six healthy adult Standardbred geldings were administered AMPT (40 mg/kg BW, orally) or placebo in a randomised crossover study design. Clinical examination findings were recorded, and blood samples were collected for up to 6 h after administration of AMPT or placebo, for measurement of blood glucose, plasma ACTH and cortisol concentrations, and plasma metabolomic analysis. Plasma prolactin concentration was determined as a proxy index of central dopamine reduction. No adverse clinical effects were detected after oral administration of AMPT, with heart rate, mean arterial pressure and blood glucose concentration not differing between AMPT treatment or placebo. Plasma prolactin concentration peaked 1 h after AMPT administration before returning to baseline at 2 h (for five horses) or 6 h (for one horse). Metabolomic analysis demonstrated a reduction in plasma dopamine (0.72-fold change; P=0.016) 1 h after AMPT treatment. Plasma ACTH and cortisol concentrations were not different between AMPT and placebo over time. A few metabolites associated with ketogenesis were increased, and certain amino acids decreased, at 1 h compared with baseline, for both AMPT treatment and placebo. Therefore, AMPT was effective in reducing both central and circulating dopamine concentrations in healthy horses following a single oral dose. Further pharmacokinetic and pharmacodynamic studies are warranted to optimise the dose and duration of AMPT treatment to achieve longer-term dopamine reduction. Plasma metabolomic findings suggested an interruption to energy flux at the time of sample collection, which may be relevant to nutritional studies in horses and warrants further investigation.

A novel approach to tyrosinase-based biosensors: Electrode reactions and biological measurement

This study introduces a novel tyrosinase-based biosensor designed to simultaneously detect tyrosinase, tyrosine, L-DOPA, and L-DOPA quinone. The biosensor, designated as GCE/GNP/Cys/Chit/Tyrase, was developed by immobilizing tyrosinase on a modified glassy carbon electrode (GCE) that incorporates electrodeposited gold nanoparticles, cysteine, and chitosan. The morphology of the biosensor was characterized using scanning electron microscopy (SEM). The electrochemical behaviors of the biosensor were explored in response to the target analytes. Key analytical characteristics were assessed, including linear range, sensitivity, selectivity, limits of detection and quantification, long-term stability, repeatability, reproducibility, electrochemically active surface area, and charge transfer behavior. The biosensor demonstrated a linear response range of 1–120 μM, with an impressive sensitivity of 200.4 mA.Lmol−1cm−2 and a detection limit of 27 μM. This study provides a comprehensive evaluation of the analytical features of tyrosinase-based biosensors. Additionally, the biosensor was applied to quantify dopamine in brain tissue, utilizing a calibration curve derived from the fabricated biosensor. The dopamine concentration measured in five Wistar rats was 35 ± 2.75 μM, reflecting the mean and standard deviation, respectively. These results confirm the biosensor's capability for accurately detecting this critical neurotransmitter in the brains of Wistar rats. This investigation underscores the potential of tyrosinase-based biosensors for diverse analytical applications in biological samples.

Modulation of tenofovir by probenecid: Impact on drug, interleukin-1β, and dopamine concentration in the prefrontal cortex and cerebellum

The blood–brain barrier’s limited permeability to tenofovir restricts its ability to clear HIV from the brain. Probenecid acting as an adjuvant increases tenofovir concentrations in plasma and the kidneys thereby enhancing its therapeutic effect. However, the probenecid effect on brain tenofovir concentration and possible adverse effects remains poorly understood. We investigated the effect of probenecid co-administered tenofovir on tenofovir brain concentration, interleukin-1β (IL-1β) and dopamine concentration in the prefrontal cortex (PFC) and the cerebellum. Ninety-six male BALB/c mice were divided into four groups viz: a control group, Tenofovir disoproxil fumarate (TDF) treated, probenecid treated, and TDF + probenecid treated. We orally administered a single dose of TDF (5 mg/kg), and probenecid (8.3 mg/kg), and sacrificed six mice per group after 1 h, 4 h, and 6 h post-treatment to collect plasma, PFC, and cerebellar tissue. Co-administered tenofovir increased tenofovir concentration, peaking at 6 h with the cerebellum having the highest concentration. This suggests that probenecid enhanced the entry of tenofovir into the brain. Tenofovir alone increased IL-1β concentration at all intervals post-administration, while probenecid alone had no impact on IL-1β concentration. Co-administered tenofovir also increased IL-1β concentration. Probenecid’s limited impact on IL-1β concentration following co-administration suggests that its anti-inflammatory properties may require more than 6 h to have an effect. Furthermore, neither tenofovir nor probenecid affected dopamine concentration. In conclusion, probenecid enhances the concentration and retention of tenofovir in the brain, making it a possible pharmacokinetic enhancer. However, its anti-inflammatory effects may require a longer duration to fully manifest.

Dopamine and D1 receptor in hippocampal dentate gyrus involved in chronic stress-induced alteration of spatial learning and memory in rats

There is increasing evidence that chronic stress (CS), which occurs when the body is exposed to prolonged stressors, significantly impairs learning and memory. Dopamine (DA) plays a critical role in learning and memory in the hippocampus through the activation of D1-like receptors (D1R). However, the specific roles of DA and D1R in the hippocampal dentate gyrus (DG), particularly in relation to CS-induced changes in spatial learning and memory, are not well understood. In this study, we established a CS rat model through the random application of various stressors. We assessed spatial learning and memory using the Morris water maze (MWM) and measured DA concentration and the amplitude of field excitatory postsynaptic potentials (fEPSP) in the DG during the MWM test in freely moving rats. We also examined the involvement of D1R in spatial learning and memory by microinjecting its antagonist (SCH23390) into the DG, and then analyzed the expressions of phosphorylated (p-) Ca2+/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), and cAMP-response element binding protein (CREB) in the DG using western blot. During the MWM test, compared with the control group, the escape latency was increased, and the percentage of distance in target quadrant and the number of platform crossings were decreased, in addition, the increase of fEPSP amplitude in the DG was significantly attenuated in CS group. In the control group, the DA concentration in the DG was significantly increased during the MWM test, and this response was enhanced in the CS group. Microinjection of SCH23390 into the DG significantly improved the spatial learning and memory impairments in CS rats, and reversed the inhibitory effect of CS on increase of fEPSP amplitude in the DG during the MWM test. Furthermore, SCH23390 partially reversed the inhibitory effects of CS on the expressions of p-CaMKII, p-PKA, and p-CREB in the DG. Our findings suggest that overactivation of the DA-D1R system in the hippocampal DG impairs spatial learning and memory and related synaptic plasticity in CS rats via downregulation of PKA-CREB signaling pathway.

Direct conversion of human umbilical cord mesenchymal stem cells into dopaminergic neurons for Parkinson's disease treatment

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor deficits due to the depletion of nigrostriatal dopamine. Stem cell differentiation therapy emerges as a promising treatment option for sustained symptom relief. In this study, we successfully developed a one-step differentiation system using the YFBP cocktail (Y27632, Forskolin, SB431542, and SP600125) to effectively convert human umbilical cord mesenchymal stem cells (hUCMSCs) into dopaminergic neurons without genetic modification. This approach addresses the challenge of rapidly and safely generating functional neurons on a large scale. After a 7-day induction period, over 80 % of the cells were double-positive for TUBB3 and NEUN. Transcriptome analysis revealed the dual roles of the cocktail in inducing fate erasure in mesenchymal stem cells and activating the neuronal program. Notably, these chemically induced cells (CiNs) did not express HLA class II genes, preserving their immune-privileged status. Further study indicated that YFBP significantly downregulated p53 signaling and accelerated the differentiation process when Pifithrin-α, a p53 signaling inhibitor, was applied. Additionally, Wnt/β-catenin signaling was transiently activated within one day, but the prolonged activation hindered the neuronal differentiation of hUCMSCs. Upon transplantation into the striatum of mice, CiNs survived well and tested positive for dopaminergic neuron markers. They exhibited typical action potentials and sodium and potassium ion channel activity, demonstrating neuronal electrophysiological activity. Furthermore, CiNs treatment significantly increased the number of tyrosine hydroxylase-positive cells and the concentration of dopamine in the striatum, effectively ameliorating movement disorders in PD mice. Overall, our study provides a secure and reliable framework for cell replacement therapy for Parkinson's disease.