Increase In Dopamine Concentration Research Articles

Wuzi Yanzong pill attenuates MPTP-induced Parkinson’s Disease via PI3K/Akt signaling pathway

Wuzi Yanzong Pill (WYP) was found to play a protective role on nerve cells and neurological diseases, however the molecular mechanism is unclear. To understand the molecular mechanisms that underly the neuroprotective effect of WYP on dopaminergic neurons in Parkinson's disease (PD). PD mouse model was induced by the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Gait and hanging tests were used to assess motor behavioral function. Immunofluorescence assay was used to determine TH-positive neurons in substantia nigra (SN). Apoptosis, dopamine and neurotrophic factors as well as expression of PI3K/Akt pathway were detected by TUNEL staining, ELISA and western blotting, respectively. First, it was observed that WYP intervention improved abnormal motor function in MPTP-induced PD model, alleviated the loss of TH+ neurons in SN, and increased dopamine content in brain, revealing a potential protective effect. Second, network pharmacology was used to analyze the possible targets and pathways of WYP action in the treatment of PD. A total of 126 active components related to PD were screened in WYP, and the related core targets included ALB, GAPDH, Akt1, TP53, IL6 and TNF. Particularly, the effect of WYP on PD may be medicate through PI3K/Akt signaling pathway and apoptotic regulation. The WYP treated PD mice had higher expression of p-PI3K, p-Akt and Bcl-2 but lower expression of Bax and cleaved caspase-3 than the non-WYP treated PD mice. Secretion of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) were also increased in the treated mice. WYP may inhibit apoptosis and increase the secretion of neurotrophic factor via activating PI3K/ Akt signaling pathway, thus protecting the loss of dopamine neurons in MPTP-induced PD mice.

Phase transformation and electrochemical charge storage properties of vanadium oxide/carbon composite electrodes synthesized via integration with dopamine

AbstractChemically preintercalated dopamine (DOPA) molecules were used as both a reducing agent and a carbon precursor to prepare δ‐V2O5·nH2O/C, H2V3O8/C, VO2(B)/C, and V2O3/C nanocomposites via hydrothermal treatment or hydrothermal treatment followed by annealing under Ar flow. We found that the phase composition and morphology of the produced composites are influenced by the DOPA:V2O5 ratio used to synthesize (DOPA)xV2O5 precursors through DOPA diffusion into the interlayer region of the δ‐V2O5·nH2O framework. The increase of DOPA concentration in the reaction mixture led to a more pronounced reduction of vanadium and a higher fraction of carbon in the composites’ structure, as evidenced by X‐ray photoelectron spectroscopy and Raman spectroscopy measurements. The electrochemical charge storage properties of the synthesized nanocomposites were evaluated in Li‐ion cells with nonaqueous electrolytes. δ‐V2O5·nH2O/C, H2V3O8/C, VO2(B)/C, and V2O3/C electrodes delivered high initial capacities of 214, 252, 279, and 637 mAh g–1, respectively. The insights provided by this investigation open up the possibility of creating new nanocomposite oxide/carbon electrodes for a variety of applications, such as energy storage, sensing, and electrochromic devices.

Dopamine Enhances the Resistance of Apple to Valsa mali Infection.

Apple Valsa canker is considered one of the most serious apple diseases. Dopamine is a catecholamine with key physiological functions in plants. Tyrosine decarboxylase (TYDC) is not only involved in the synthesis of dopamine in plants but may also play an important role in the resistance of plants to pathogen infection. In this study, we show that 100-μM exogenous dopamine application and Malus domestica TYDC (MdTYDC) overexpression (or overexpressing, OE) enhances the resistance of apple to Valsa mali infection, likely because the increased dopamine content reduces the accumulation of H2O2 and increases the accumulation of phenolic compounds and salicylic acid (SA) in dopamine-treated and OE apple plants. The activity of chitinase and β-1, 3-glucanase and the expression of SA-related genes were induced more strongly by V. mali in dopamine-treated and OE apples. The dopamine content was significantly higher in dopamine-treated and OE apples than in their respective controls under both normal and inoculated conditions (P < 0.05). Overall, these findings indicate that the application of exogenous dopamine and the OE of MdTYDC may enhance the resistance of apples to V. mali infection by altering the dopamine content, which improves antioxidant capacity, promotes the accumulation of phenolic compounds and SA, and enhances the activity of disease resistance-related proteins.

Dopamine concentration-dependent surface modification for gaining carbon fiber composites with enhanced interfacial adhesion

Self-assembly process of dopamine concentration-dependent polydopamine (PDA) on graphitized carbon fiber is elucidated, as well as its effects on interfacial adhesion of composites. With the increase of dopamine concentration, active PDA nanospheres in Tris-solution first adhere to fiber surface to form a thin film, then accompanies with the creation of ever-increasing PDA aggregates instead of continuing to form a thicker PDA film. The optimal dopamine additive amount is 0.3 g for 52.6% IFSS improvement by analogy to untreated fiber, because of the greatly enhanced epoxy wettability from the contribution of the synergistic actions of more polar groups and rougher surface. Less and higher dopamine additions go against substantial increment in IFSS, especially for higher ones that large-sized PDA nanospheres are apt to induce stress concentration, sacrificing the contribution by more active groups.

Changes in Brain Dopamine Extracellular Concentration after Ethanol Administration; Rat Microdialysis Studies.

The purpose of this review is to evaluate microdialysis studies where alterations in the dopaminergic system have been evaluated after different intoxication states, in animals showing preference or not for alcohol, as well as during alcohol withdrawal. Ethanol administration induces varying alterations in dopamine microdialysate concentrations, thereby modulating the functional output of the dopaminergic system. Administration of low doses of ethanol, intraperitoneally, intravenously, orally or directly into the nucleus accumbens, NAc, increases mesolimbic dopamine, transmission, as shown by increases in dopamine content. Chronic alcohol administration to rats, which show alcohol-dependent behaviour, induced little change in basal dopamine microdialysis content. In contrast, reduced basal dopamine content occurred after ethanol withdrawal, which might be the stimulus to induce alcohol cravings and consumption. Intermittent alcohol consumption did not identify any consistent changes in dopamine transmission. Animals which have been selectively or genetically bred for alcohol preference did not show consistent changes in basal dopamine content although, exhibited a significant ethanol-evoked dopamine response by comparison to non-preference animals. Microdialysis has provided valuable information about ethanol-evoked dopamine release in the different animal models of alcohol abuse. Acute ethanol administration increases dopamine transmission in the rat NAc whereas chronic ethanol consumption shows variable results which might reflect whether the rat is prior to or experiencing ethanol withdrawal. Ethanol withdrawal significantly decreases the extracellular dopamine content. Such changes in dopamine surges will contribute to both drug dependence, e.g. susceptibility to drug withdrawal, and addiction, by compromising the ability to react to normal dopamine fluctuations.

Systemic oxytocin increases glutamate efflux in the nucleus accumbens core of cocaine-experienced male and female rats but only increases dopamine efflux in males

Oxytocin attenuates cocaine-seeking when administered both systemically and directly into the nucleus accumbens core. This effect is blocked by intra-accumbens antagonism of mGlu2/3 and, together with our finding that intra-accumbens oxytocin increases glutamate concentrations in this brain region, indicates that pre-synaptic regulation of glutamate release by oxytocin influences cocaine relapse. However, mGlu2/3 receptors also regulate dopamine release in the nucleus accumbens. Here we aimed to determine whether systemic oxytocin increases glutamate and dopamine concentrations in the nucleus accumbens core of cocaine-experienced and cocaine-naïve male and female rats. A subset of rats self-administered cocaine (0.5 mg/kg/infusion) and then underwent extinction training for 2–3 weeks. Rats were implanted with microdialysis probes in the accumbens core and samples were collected for a baseline period, and following saline (1 mL/kg), and oxytocin (1 mg/kg, IP) injections. Locomotion was assessed during microdialysis. In cocaine-experienced rats, oxytocin increased glutamate concentrations in the accumbens core to the same extent in males and females but only increased dopamine concentrations in male rats. Oxytocin did not alter glutamate levels in cocaine-naïve rats. Oxytocin did not produce sedation. These results extend previous findings that systemic oxytocin increases nucleus accumbens dopamine in a sex-specific manner in cocaine-experienced rats. These data are the first to find that systemic oxytocin increases nucleus accumbens glutamate after cocaine experience, providing a mechanism of action by which oxytocin attenuates the reinstatement of cocaine seeking in both male and female rats.

Ninjin'yoeito, a traditional Japanese medicine, increases dopamine content in PC12 cells.

Dementia is exacerbated by loss of appetite and amotivation, and recent studies have indicated that ninjin'yoeito improves anorexia and amotivation. Previous studies suggest that ninjin'yoeito inhibits dopamine-metabolizing enzymes and enhances dopamine signaling. However, whether ninjin'yoeito increases dopamine content in living cells remains unclear. Here, PC12 cells were used to examine whether ninjin'yoeito affects the dopamine metabolic pathway. Dopamine content significantly increased 3 h after treatment ninjin'yoeito extract. Concomitantly, the levels of 3-methoxytyramine and 3,4-dihydroxyphenylacetic acid were significantly reduced. The effects of components of ninjin'yoeito on the dopamine metabolic pathway were also assessed. Treatment with onjisaponin B, nobiletin, and schisandrin, and the ingredients of Polygalae Radix, Citri Unshiu Pericarpium, and Schisandrae Fructus increased dopamine content and decreased its metabolite content in the culture media. Our findings suggest that ninjin'yoeito improves anorexia and amotivation by inhibiting metabolic enzyme and increasing the dopamine content in cells.

Effects of β-Phenylethylamine on Psychomotor, Rewarding, and Reinforcing Behaviors and Affective State: The Role of Dopamine D1 Receptors.

Beta-phenylethylamine (β-PEA) is a well-known and widespread endogenous neuroactive trace amine found throughout the central nervous system in humans. In this study, we demonstrated the effects of β-PEA on psychomotor, rewarding, and reinforcing behaviors and affective state using the open-field test, conditioned place preference (CPP), self-administration, and ultrasonic vocalizations (USVs) paradigms. We also investigated the role of the dopamine (DA) D1 receptor in the behavioral effects of β-PEA in rodents. Using enzyme-linked immunosorbent assay (ELISA) and Western immunoblotting, we also determined the DA concentration and the DA-related protein levels in the dorsal striatum of mice administered with acute β-PEA. The results showed that acute β-PEA increased stereotypic behaviors such as circling and head-twitching responses in mice. In the CPP experiment, β-PEA increased place preference in mice. In the self-administration test, β-PEA significantly enhanced self-administration during a 2 h session under fixed ratio (FR) schedules (FR1 and FR3) and produced a higher breakpoint during a 6 h session under progressive ratio schedules of reinforcement in rats. In addition, acute β-PEA increased 50-kHz USV calls in rats. Furthermore, acute β-PEA administration increased DA concentration and p-DAT and TH expression in the dorsal striatum of mice. Finally, pretreatment with SCH23390, a DA D1 receptor antagonist, attenuated β-PEA-induced circling behavior and β-PEA-taking behavior in rodents. Taken together, these findings suggest that β-PEA has rewarding and reinforcing effects and psychoactive properties, which induce psychomotor behaviors and a positive affective state by activating the DA D1 receptor in the dorsal striatum.

Carbon nanospheres modified with WO2-NaxWO3 nanoparticles for highly sensitive electrochemical detection of dopamine

WO2-NaxWO3 nanoparticles modified carbon spheres (WO2-NaxWO3/CSs) composite has been successfully synthesized by simple hydrothermal synthesis and high temperature calcination, and highly selective detection of dopamine (DA) was performed. The existence of WO2-NaxWO3 was confirmed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Raman spectrum. Meanwhile, it can be seen from transmission electron microscopy (TEM) images that WO2-NaxWO3 was modified on the surface of carbon spheres in the form of nanometer-scaled particles. Cyclic voltammetry (CV) showed that the glassy carbon electrode modified by WO2-NaxWO3/CSs composite had strong electrocatalytic activity for DA oxidation, and a non-enzyme DA electrochemical sensor based on this material was constructed. Under the best conditions, the differential pulse voltammetry (DPV) signals of proposed sensor linearly increased with the increase of DA concentration in the range of 0.004 ~ 15.4 μM and 15.4 ~ 106.4 μM, with high sensitivity of 19.335 μA·μM−1·cm−2 and 3.151 μA·μM−1·cm−2, respectively, and a low limit of detection (LOD) of 1.3 nM (S/N = 3) and a limit of quantification (LOQ) of 4.3 nM were obtained. Furthermore, the sensor had good selectivity and satisfactory reproducibility and good stability for DA detection (RSD = 2.50%). It was successfully used to detect DA in animal serums, its recovery rate was between 1.10% and 2.91%, showing potential practical application value.

Aqueous dispersion and tuning surface charges of polytetrafluoroethylene particles by bioinspired polydopamine-polyethyleneimine coating via one-step method.

We propose a surface modification of poorly dispersive polytetrafluoroethylene (PTFE) particles via bioinspired polydopamine–polyethyleneimine (PDA–PEI) which conferred PTFE particles a uniform dispersion in aqueous medium. With increasing dopamine concentration in the reaction solution, dispersity of PTFE particles improved and the surface charges of particles changed from negative to positive due to an increase of surface coverage of PDA–PEI layers. Simplicity of the method here outlines an attractive route for surface modification of inert surfaces useful for large-scale applications.

FGF, Mechanism of Action, Role in Parkinson's Disease, and Therapeutics.

Parkinson’s disease (PD) is a neurodegenerative disease associated with severe disability and adverse effects on life quality. In PD, motor dysfunction can occur, such as quiescence, muscle stiffness, and postural instability. PD is also associated with autonomic nervous dysfunction, sleep disorders, psychiatric symptoms, and other non-motor symptoms. Degeneration of dopaminergic neurons in the substantia nigra compact (SNPC), Lewy body, and neuroinflammation are the main pathological features of PD. The death or dysfunction of dopaminergic neurons in the dense part of the substantia nigra leads to dopamine deficiency in the basal ganglia and motor dysfunction. The formation of the Lewy body is associated with the misfolding of α-synuclein, which becomes insoluble and abnormally aggregated. Astrocytes and microglia mainly cause neuroinflammation, and the activation of a variety of pro-inflammatory transcription factors and regulatory proteins leads to the degeneration of dopaminergic neurons. At present, PD is mainly treated with drugs that increase dopamine concentration or directly stimulate dopamine receptors. Fibroblast growth factor (FGF) is a family of cellular signaling proteins strongly associated with neurodegenerative diseases such as PD. FGF and its receptor (FGFR) play an essential role in the development and maintenance of the nervous system as well as in neuroinflammation and have been shown to improve the survival rate of dopaminergic neurons. This paper summarized the mechanism of FGF and its receptors in the pathological process of PD and related signaling pathways, involving the development and protection of dopaminergic neurons in SNPC, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. It provides a reference for developing drugs to slow down or prevent the potential of PD.

Ferrocene Functionalized Gold Nanoparticles on Carbon Nanotube Electrodes for Portable Dopamine Sensor

Introduction Abnormal dopamine levels lead to severe diseases and disorders, including Parkinson's disease, Alzheimer's disease, and schizophrenia [1]. There is a need for sensitive and cost-effective dopamine sensors to provide rapid diagnosis at the point of care. Several approaches, such as high-performance liquid chromatography-mass spectrometry, fluorescence, and chemiluminescence based sensors, have been reported for dopamine detection with good sensitivity. However, these techniques generally are tedious, time-consuming, require sophisticated instruments, and thus not suitable for point of care (POC) testing. On the contrary, electrochemical sensors are promising due to their numerous advantages, including simple operation, faster response, low-cost, and accessibility for onsite monitoring. In addition, tracing dopamine, an electroactive molecule, with an electrochemical technique is also favorable. However, dopamine's electrochemical oxidation is often disrupted by the interference from other electroactive molecules (e.g., ascorbic acid, uric acid) due to their overlapping oxidation peak potentials and the higher physiological concentrations comparing to dopamine in biological fluids.A wide range of chemically modified electrodes is explored to improve the electrocatalytic capability towards dopamine oxidation. In this regard, the modification of electrodes with carbon-based nanomaterials and redox mediators has gained keen interest. For instance, ferrocene (Fc) and its derivatives can catalyze the oxidation or reduction of several biomolecules with advantages of fast response, stable redox states, electrochemical reversibility, and regeneration at low potential [2]. However, immobilization of Fc on electrodes remains challenging due to their weak adsorption and low stability. In this work, we create a new sensor by decorating ferrocene (Fc) functionalized gold nanoparticles (AuNPs) on carbon nanotube (CNT) to form an electroactive composite (Fc-AuNPs-CNT) for electrochemical detection of dopamine. The Fc functionalized AuNPs provide excellent catalytic activity towards dopamine with improved electron conductivity. Furthermore, the larger active surface area provided by CNT also enhances the dopamine reaction on the electrode. Method The synthesis of AuNPs decorated multiwall CNT (MWCNT) was obtained through citrate reduction. During the pre-mixture of MWCNT and chloroauric acid (HAuCl4), HAuCl4 molecules are absorbed on the MWCNT and initiate the growth of AuNPs upon the addition of sodium citrate at room temperature. The AuNP surfaces were then functionalized with cysteamine (Cys) for the conjugation of ferrocene carboxaldehyde (Fc-CHO), leading to a Fc-AuNPs-CNT nanocomposite. The resulting nanocomposite was drop-casted with chitosan (CS) as a binder onto a screen-printed carbon electrode (SPE). The film morphology and elemental composition were characterized by scanning electron microscopy (SEM) and energy dispersive X-Ray analysis (EDX). Electrochemical responses were obtained with cyclic voltammetry (CV). Results and discussion The Fc-AuNPs-CNT composite exhibits a pair of stable and well-defined redox peaks in CV contributed by the ferrocene and ferrocenium (Fc/Fc+) redox couples. The Fc element peak in EDX further confirms the successful conjugation of Fc towards AuNPs. The Fc-AuNPs-CNT composite was demonstrated for dopamine sensing within 10 s incubation. Dopamine oxidation peak appears around +0.3V in anodic sweep, and its two reduction peaks appear around 0.15V and -0.25V. Increasing dopamine concentrations raises both oxidation and reduction currents. Compared with the AuNPs-CNT composite, Fc-AuNPs-CNT composite exhibits ~3 times higher response for the oxidation of 1 mM dopamine. The synergistic effects of Fc-AuNPs-CNT improve electron transfer rate between dopamine and electrode and convey superior electrocatalytic activity toward dopamine oxidation and reduction. The proposed sensor has a dynamic range of detection ranging from 10 µM to 1 mM dopamine and a low detection limit of 3 µM. The sensor also provides selective detection to discriminate ascorbic acid, glucose, hydrogen peroxide. The electrochemical property of Fc remains stable under repetitive potential sweep. No significant change in peak intensity was observed. Conclusion The Fc-AuNPs-CNT nanocomposite-based sensor presented here provides simple, cost-effective, portable, and rapid detection of dopamine with good sensitivity and selectivity, making it suitable for POC testing.

Dopamine sheathing facilitates the anisotropic growth of lysozyme crystals

The effect of dopamine (DA) on the nucleation and growth rate of hen egg white lysozyme (HEWL) crystals was studied using polarizing microscopy, powder X-ray diffraction, fluorescence spectroscopy, circular dichroism, and dynamic light scattering, in combination with molecular dynamic simulations. DA increased the solubility of HEWL and promoted the nucleation of HEWL crystals. Crystallization experiments also showed that the shape of HEWL crystals changed from a block to a rod with DA addition, which was attributed to the variation in the growth rates of their neighboring planes. The growth of (101) plane was slightly inhibited and decreased from 3.9 to 3.1 nm/s while the growth rate of (110) decreased significantly from 4.1 to 1.8 nm/s with an increase of DA content. Molecular dynamic simulations indicated that hydrogen bonding and hydrophobic interactions between DA and HEWL were mainly concentrated in the pocket region of HEWL, which enhanced the hydrophilicity and steric hindrance of the area, modulated the assembly behavior of HEWL, and resulted in the anisotropic growth of HEWL crystals. These results suggest that small organic molecules in vivo are an important factor in modulating protein crystal morphology by adjusting the conformational structure of protein molecules.

Effect of dopamine-modified expanded vermiculite on phase change behavior and heat storage characteristic of polyethylene glycol

The surfaces of functionalized modified minerals play important role in promoting the phase change behavior of phase change materials (PCMs) and improving their heat storage characteristics. In this work, the strategy of dopamine modification was adopted to solve the current problem that the measured latent heats of expanded vermiculite (EVM)-based composite PCMs were significantly lower than the calculated values during the phase change process. A series of novel polyethylene glycol (PEG)/EVM-dopamine (EVMX) form-stable composite PCMs (PEX fs-CPCMs) with efficient phase change and enhanced latent heat were prepared after encapsulating PEG into the pores of EVMX. It was found that the encapsulation capacity (~19%) and latent heats during melting (~75%) and solidification processes (~67%) increased with increasing dopamine concentration. In addition, the difference between measured and calculated latent heats of PEX fs-CPCMs gradually decreased with increasing dopamine concentration. Specially, the latent heat of PE4.0 during melting process was even higher than the calculated value, indicating that PEG could freely undergo phase change on the surfaces of EVMX. The strong interactions between PEG molecules and surfaces of EVM could be regulated by amination modification and new suitable combination approaches were constructed, so that the confinement effect of surfaces was weakened, which was responsible for the promoted phase change behavior, improved form stabilization and enhanced latent heat of PEG. Moreover, the PEX fs-CPCMs showed excellent chemical compatibility, thermal reliability and stability.

Ionic liquid tuned titanium dioxide nanostructures as an efficient colorimetric sensing platform for dopamine detection

Dopamine is a neurotransmitter distributed in the central and peripheral nervous system, its lower or higher production results in various pathological disorders. Various nanoparticles systems have been used in the sensing of dopamine while in the present work ionic liquid tuned titanium dioxide nanoparticles (TiO2 NPs) was first time evaluated in colorimetric detection of dopamine. TiO2 NPs have been synthesized by hydrothermal process and analyzed by different characterization techniques such as FTIR, XRD, and SEM that confirmed the desired synthesis. 1-H-3-methylimidazolium acetate (ionic liquid-a known conducting species) was prepared by the neutralization method. Colorimetric change in color from pinkish grey to reddish-brown with an increase in dopamine concentration was analyzed using a UV–Vis spectrophotometer. To optimize the protocol various parameters like nanoparticles loading, conc. of dopamine etc were optimized. The quantification and limit of detection for the proposed sensor were calculated as 2.55 × 10−7 M and 7.67 × 10−8 M respectively, and 1 × 10−8–3.6 × 10−6 M linear range with an R2 value of 0.9998. At an optimum temperature of 25 °C and at pH 12 the proposed sensor response time was just 4 min for dopamine detection. The proposed sensor has been also used for the dopamine detection in physiological solution. The proposed sensor showed good sensitivity and selectivity for dopamine sensing.

Fluorescent Carbon Dots Prepared from Hazelnut Kohl as an Affordable Probe for Determination of Dopamine.

In this investigation, a simple, green and facile fluorescence mrtod using carbon dots (CDs) of hazelnut kohl is described for selective detection of dopamine (DA). The sensing system is based on hazelnut kohl (the black soot of kohl) which is used as a carbon source. Generally, kohl is a traditional eye cosmetic that used in different parts of the world and synthesized by the combustion process like burning natural materials. Here, it has been proven that black soot (kohl) obtained from hazelnut has a carbon dot structure and can be used for sensory applications. Some characterization methods are carried out to reveal the kohl structure. Also, the photoluminescence properties of the prepared CDs of kohl are investigated. It is found that the size of CDs is 2-4nm. Besides, under the optimal conditions, the fluorescence of CDs is used for DA determination. CDs fluorescence intensity is decreased linearly with the increase of DA concentration. By using the fluorescence dependency toward the DA concentration, DA can be determined in the range 0.5-30μM with the limit of detection of 0.30μM. Finally, this method is successfully applied to discriminate the DA in the real samples (healthy human serum and cerebrospinal fluid (CSF)) which shows acceptable efficiently for diagnostic purposes. The fluorescence of carbon dots, prepared from Hazelnut Kohl, is quenched in the presence of dopamine.

Effects of N-acetylcysteine treatment on ethanol’s rewarding properties and dopaminergic alterations in mesocorticolimbic and nigrostriatal pathways

Recent reports have shown that N-acetylcysteine (N-AC) has beneficial effects in the treatment of cocaine and nicotine abuse. Considering the similar neurobiologic mechanisms involved in the development of addiction to different drugs, N-AC treatment could be useful in the treatment of ethanol abuse. The rewarding properties of the drugs of abuse plays an important role in the development of addiction and can be studied using the conditioned place preference (CPP) paradigm. Thus, to study the effects of N-AC treatment in the rewarding effects of ethanol, we investigated the effects of N-AC administration in the ethanol-induced CPP and neurochemical alterations within the mesocorticolimbic and the nigrostriatal dopaminergic pathways. Adult male Swiss mice were pretreated with N-AC (60 or 120 mg/kg intraperitoneal) and tested for the development, expression, or extinction of the ethanol-induced CPP. Another cohort of animals received N-AC (60 or 120 mg/kg intraperitoneal) 2-h before an acute administration of ethanol and had their brains removed for dopamine and its metabolites quantification in the mesocorticolimbic and nigrostriatal pathways. Pretreatment with N-AC (120 mg/kg) blocked the development of ethanol-induced CPP. On the other hand, N-AC at both doses did not alter the expression nor the extinction of ethanol-induced CPP. N-AC increased 3,4-dihydroxyphenylacetic acid content in the medial prefrontal cortex and dopaminergic turnover within the substantia nigra. Besides that, there was an increase in dopamine content in the nucleus accumbens of ethanol-treated animals. In summary, N-AC treatment blocked the development of ethanol CPP, without altering ethanol effects on dopaminergic neurotransmission.

Dopamine and Striatal Neuron Firing Respond to Frequency-Dependent DBS Detected by Microelectrode Arrays in the Rat Model of Parkinson's Disease.

(1) Background: Deep brain stimulation (DBS) is considered as an efficient treatment method for alleviating motor symptoms in Parkinson’s disease (PD), while different stimulation frequency effects on the specific neuron patterns at the cellular level remain unknown. (2) Methods: In this work, nanocomposites-modified implantable microelectrode arrays (MEAs) were fabricated to synchronously record changes of dopamine (DA) concentration and striatal neuron firing in the striatum during subthalamic nucleus DBS, and different responses of medium spiny projecting neurons (MSNs) and fast spiking interneurons (FSIs) to DBS were analyzed. (3) Results: DA concentration and striatal neuron spike firing rate showed a similar change as DBS frequency changed from 10 to 350 Hz. Note that the increases in DA concentration (3.11 ± 0.67 μM) and neural spike firing rate (15.24 ± 2.71 Hz) were maximal after the stimulation at 100 Hz. The MSNs firing response to DBS was significant, especially at 100 Hz, while the FSIs remained stable after various stimulations. (4) Conclusions: DBS shows the greatest regulatory effect on DA concentration and MSNs firing rate at 100 Hz stimulation. This implantable MEA in the recording of the neurotransmitter and neural spike pattern response to DBS provides a new insight to understand the mechanism of PD at the cellular level.

Cognitive impairment by non‐insulin‐dependent diabetes mellitus was attenuated by dietary supplements of marble vine (Dioclea reflexa) and plantain (Musa paradisiaca) dough meals in albino rats

This study investigates the protective effect of formulated marble vine/plantain dough meals on cognitive impairment in diabetic rats. Wistar rats were divided into eight groups (n=6) and fed with HFD for 14days and a single dose of streptozotocin intraperitoneally on the 14th day (except control rats). Diabetic rats were treated with formulated diets and metformin. The ameliorative effect of the formulated doughs on cerebral damage in diabetic rats with respect to weight gain/loss, glucose and insulin levels, oxidative damage, neurological dysfunction, and histological alterations were assessed. The formulated diet had high protein and fiber content values ranged from 13.00 to 25.04g/100g and from 5.23 to 6.20g/100g, respectively compared to the control. Blood glucose level was observed, thereby mitigating the cerebral oxidative damage. The diet significantly ameliorated the neurological dysfunction as adjudged by increased dopamine concentration and lowered acetylcholinesterase activity; results were also supported by the outcomes from brain histopathological study. PRACTICAL APPLICATIONS: Underutilized leguminous seeds such as marble vine seeds are known for their nutraceutical potentials due to their numerous biochemical components. The study provides preliminary information on the potential of marble vine/plantain functional dough meals in the management of neurological complications resulting from type 2 diabetes mellitus in albino rats. Generally, the formulated doughs possess neuroprotective potentials in preventing neurological complications arising from diabetes. However, the effect of marble vine-plantain dough meal in managing the brain damage should be further investigated through the clinical trials before development for pharmaceutical applications.

Overexpression of the tyrosine decarboxylase gene MdTyDC confers salt tolerance in apple

Dopamine mediates numerous physiological processes in plants. Tyrosine decarboxylase (TyDC, EC 4.1.1.28) is a common enzyme prevalent in plants and mediates numerous secondary reactions, but little is known about the role of TyDC in the dopamine derivative biosynthesis and function in salt tolerance. Here, apple and apple calli were utilized to study the function of MdTyDC under salt conditions. Overexpression of MdTyDC (OE) significantly increased dopamine content in apple and apple calli. The OE apple lines exhibited increased growth performance and higher photosynthetic capacity and contained more photosynthetic pigments than those of the wild-type lines (WT) under salt conditions. The OE lines had lower H2O2 and O2.− according to DAB and NBT-staining compared to the WT lines. Overexpressing MdTyDC enhanced antioxidant enzyme activities and maintained ion homeostasis, as well as increased the expression levels of associated genes. Furthermore, overexpressing MdTyDC enhanced proline content, increased fresh weight, and reduced malondialdehyde (MDA) content in apple calli; however, RNA interference lines showed higher MDA content and lower fresh weight and proline content. Our findings demonstrate that overexpressing MdTyDC induced higher dopamine levels and increased scavenging of reactive oxygen species and the Na+/K+ balance; thus, enhancing salt tolerance.